Synthesis
of
highly
substituted
dienes
via
silaboration
and
cross­coupling
reactions


 
 
 
 Kungliga
Tekniska
Högskolan
‐
The
Royal
Institute
of
Technology
 
 
 
 
 
 


Synthesis
of
highly
substituted
dienes
via
silaboration
and
cross­

coupling
reactions



 


Degree
project
in
Organic
Chemistry


Master
in
Molecular
Science
and
Engineering






 Department
of
Chemistry
‐
Organic
Chemistry
 Teknikringen
30
 S‐100
44
Stockholm
 
 
 
 
 
 
 Presented
by
Victor
Östlund
 victoro@kth.se
 
 
 
 January
16th_{to
June
18}th₂₀₁₂ 
 
 
 Tutor:
Doctor
Hui
Zhou
 Supervisor:
Professor
Christina
Moberg




Table
of
Contents


LIST
OF
ABBREVIATIONS...3
 ABSTRACT...4
 1.
SCIENTIFIC
BACKGROUND...5
 2.
RESULTS
AND
DISCUSSION ...9
 A
‐
SONOGASHIRA
COUPLING... 9
 B
‐
SILABORATION... 9
 a)
Silaboration
of
1,3­enynes
in
presence
of
benzaldehyde...9
 b)
Silaboration
of
dienes
in
presence
of
benzaldehyde... 11
 c)
Silaboration
of
1,3­enynes... 12


B)
SUZUKI‐MIYAURA
CROSS‐COUPLING... 13


D)
SILVER(I)
OXIDE
ACTIVATED
CROSS‐COUPLING... 15


3.
CONCLUSION... 18


ACKNOWLEDGMENTS ... 18


EXPERIMENTAL
SECTION ... 19


GENERAL
EXPERIMENTAL
PROCEDURE... 19


A
‐
SYNTHESIS
OF
ENYNES... 19
 B
‐
SYNTHESIS
OF
SILYLBORANE
STARTING
MATERIAL... 20
 C
‐
SILABORATION
IN
PRESENCE
OF
BENZALDEHYDE... 21
 1.
Enynes... 21
 2.
Dienes... 24
 D
‐
SILABORATION
WITHOUT
ALDEHYDE... 26


E
‐
SUZUKI‐MIYAURA
COUPLING... 27


F
‐
SYNTHESIS
OF
IODOALKENES
AS
STARTING
MATERIAL
FOR
COUPLING
REACTIONS... 29


G
‐
SILVER(I)
OXIDE
ACTIVATED
CROSS‐COUPLING
OF
SILANOL... 30


H
‐
NMR
SPECTRA... 34


REFERENCES ... 49
 


List
of
Abbreviations





Abbreviation
 Meaning
 Chemical
Formula


acac
 acetylacetonate
 CH3COCHCOCH3


b.p.
 Boiling
point
 
 Bu
 Butyl
 CH3CH2CH2CH2
 Brine
 Saturated
sodium
chloride
solution
 
 cat.
 Catalyst
 
 cod
 cyclooctadiene
 (CH2)2(CH)2(CH2)2(CH)2
 DCM
 Dichloromethane
 CH2Cl2


DIBAL‐H
 Diisobutylaluminium
hydride
 [(CH3)2CHCH2]2AlH


Et
 Ethyl
 CH3CH2


EtOAc
 Ethyl
Acetate
 CH3COOCH2CH3


h
 Hour(s)
 
 iPr
 isopropyl
 CH(CH3)2
 J
 Coupling
constant
in
Hertz
(NMR)
 
 L
 Ligand
 
 Me
 Methyl
 CH3
 M
 Concentration
in
mol/L
(molar)
 
 min.
 Minute(s)
 
 mol
 Mole(s)
 
 Mw
 Molecular
weight
 
 NMR
 Nuclear
Magnetic
Resonance
 


Pd‐PEPPSI‐iPr
 [1,3‐Bis(2,6‐Diisopropylphenyl)imidazol‐2‐ylidene](3‐_{chloropyridyl)palladium(II)
dichloride} C32H40Cl3N3Pd


Ph
 Phenyl
 C6H5


PhCHO
 Benzaldehyde
 C6H5CHO


(pin)
 Pinacol
 OC(CH3)2C(CH3)2O


PPh3
 Triphenylphosphine
 P(C6H5)3
 r.t.
 Room
temperature
 
 THF
 Tetrahydrofuran
 (CH2)4O
 TLC
 Thin
Layer
Chromatography
 
 TMS
 Trimethylsilyl
 Si(CH3)3
 Tol
 Toluene
 C6H5CH3
 


Abstract





A
synthetic
approach
to
highly
substituted
dienes
has
been
investigated.
In
a
four
step
 synthesis,
a
wide
range
of
molecules
can
be
formed:
Sonogashira
coupling
between
an
 alkyne
 and
 a
 bromoalkene,
 silaboration
 of
 the
 newly
 formed
 enyne,
 Suzuki‐Miyaura
 coupling
 to
 exchange
 the
 boronic
 ester
 moiety,
 and
 silver(I)
 oxide
 activated
 cross‐ coupling
 to
 replace
 the
 silicon
 atom.
 The
 majority
 of
 final
 compounds
 are
 afforded
 in
 moderate
to
good
yields
(20‐55%
over
4
steps).
In
some
cases,
the
last
step
where
the
 silyl
moiety
is
exchanged
to
an
aromatic
ring
has
caused
some
problems:
isomerization
 and
lower
yields.



 


1.
Scientific
background






 Organic
 chemistry
 is
 a
 field
 in
 full
 expansion
 and
 new
 discoveries
 deeply
 affect
 today's
 society,
 e.g.
 to
 acquire
 better
 knowledge
 of
 the
 world,
 to
 render
 possible
 the
 synthesis
 of
 life‐saving
 drugs,
 and
 to
 fabricate
 new
 materials.
 Very
 large
 and
 complex
 molecules
such
as
some
natural
products
are
now
possible
to
be
synthesized,
something
 that
seemed
impossible
a
few
decades
ago1_{.
As
this
field
grows,
so
does
the
need
to
find} new,
cheaper
and
more
environmentally
friendly
ways
to
access
chemicals.
This
has
led
 to
the
development
of
an
immense
number
of
catalysts
rendering
otherwise
impossible
 reactions
achievable2_. 
 Over
the
past
30
years,
transition‐metal
catalysis3_{has
known
a
huge
spike
in
activity.}

It
 has
 made
 possible
 the
 formation
 of
 a
 very
 broad
 range
 of
 molecules
 and
 keeps
 revolutionizing
the
field
of
organic
chemistry.



 Boron
and
silicon
are
the
main
focus
of
this
work
and
will
therefore
be
introduced
in
 a
general
way.
Boron
is
a
nonmetallic
element
that
is
much
less
abundant
on
Earth
than
 its
 group
 13‐neighbor
 aluminum
 for
 instance.
 Boron
 occurs
 naturally
 as
 the
 minerals
 borax
 and
 kernite4_{.
 The
 most
 useful
 compound
 of
 boron
 is
 borax,
 which
 has
 many}

domestic
uses
such
as
water
softener,
cleaner,
or
mild
pesticide.
Organic
chemists
have
 shown
a
larger
interest
in
the
use
of
boron
these
last
decades
with
the
development
of
 the
Suzuki‐Miyaura
cross‐coupling
and
hydroboration
for
example5_.


 Silicon
is
one
of
the
most
abundant
elements
in
the
Earth's
crust
and
makes
up
26
per
 cent
 of
 its
 mass4_{.
 Since
 the
 development
 of
 computers
 in
 the
 late
 1900's,
 silicon
 has}

become
 immensely
 important
 to
 the
 modern
 world.
 It
 is
 used
 in
 semiconductors
 and
 optical
fibers
together
with
germanium
because
of
its
band
gap
and
therefore
its
semi
 conductive
properties.
Silicon
is
also
widely
used
in
organic
chemistry.
To
name
a
few
of
 its
applications,
it
serves
as
protective
group
for
alcohols
or
alkynes6_{and
can
undergo}

cross‐coupling
reactions7_{or
hydrosilylation}8_.


 When
 dealing
 with
 a
 synthetic
 sequence
 to
 afford
 a
 given
 molecule,
 the
 goal
 is
 to
 reduce
 the
 number
 of
 steps,
 thereby
 making
 the
 whole
 synthesis
 easier
 and
 more
 efficient.
 By
 using
 transition
 metal‐catalyzed
 heterointerelement
 additions
 to
 unsaturated
 bonds,
 two
 functionalities
 are
 added
 to
 the
 target
 molecule
 in
 one
 single
 reaction9_{.
Theses
new
groups
can
be
chosen
to
differ
in
reactivity,
which
allows
further} transformations
in
a
complex
way.
 In
particular,
addition
of
silylboranes
to
unsaturated
carbon
bonds
is
of
great
interest
 since
both
the
added
silyl
and
boryl
groups
are
helpful
in
a
synthetic
approach10_.
Scheme 1
illustrates
a
pioneering
work
in
this
field
by
Suginome
et
al.11_. 
 Scheme
1
Silaboration
of
substituted
alkynes.
11
 
 This
work
gives
access
to
a
broad
range
of
substituted
alkenes,
since
the
boronic
ester
 can
for
example
undergo
the
efficient
Suzuki
cross‐coupling,
and
thereby
be
exchanged
 Si B O O R₁ R₂ R1 Si B R2 O O

to
 an
 aryl,
 vinyl
 or
 even
 alkyne
 group
 for
 instance.
 This
 is
 also
 valid
 for
 silica
 moiety,
 which
can
be
exchange
by
Hiyama‐Denmark
coupling
to
an
aryl
group,
which
has
been
 the
case
in
this
work.



 Another
 more
 recently
 reported
 work
 deals
 with
 silaborations
 of
 1,3‐enynes12_{.
 As}

seen
on
Scheme
2,
depending
on
the
substitution
at
the
alkyne,
the
final
product
will
be
 different.
Thus,
two
versatile
types
of
molecules
(substituted
allene
or
diene)
are
made
 available.
 This
 could
 make
 a
 long
 synthesis
 sequence
 much
 easier
 in
 the
 field
 of
 total
 synthesis
for
instance.





Scheme
2
Silaboration
of
1,3­enynes12



 To
 understand
 this
 reaction,
 it
 is
 paramount
 to
 study
 the
 mechanism
 involved.
 The
 reaction
starts
via
oxidative
addition
of
the
silylborane
to
the
metal
complex
(Step
I
in
 Scheme
3).
The
next
step
is
coordination
of
the
enyne
to
the
palladium
complex,
as
these
 two
molecules
get
closer.
This
leads
to
step
III,
which
is
insertion
of
the
enyne
into
the
 palladium‐boron
bond.
If
group
R1
in
Scheme
3
is
relatively
small
(e.g.
ethyl,
butyl..),
the
 boron
group
is
added
on
the
alkyne‐carbon
bonded
to
R1,
as
is
the
case
in
Scheme
3.
On
 the
other
hand,
if
R1
is
large
(e.g.
trimethylsilyl,
tert‐butyl)
the
steric
hindrance
prevents
 this
addition,
which
gives
rise
to
another
reaction.
This
is
not
the
focus
of
this
work
and
 will
 therefore
 not
 be
 discussed
 more
 thoroughly.
 The
 reaction
 finally
 ends
 with
 reductive
elimination
of
the
newly
formed
diene.
 
 
 
 
 Scheme
3
Proposed
mechanism
for
silaboration
of
1,3­enynes13_. 
 * PhMe2Si R B(pin) large R group Pt(0) R small R group Pd(0) or Pt(0) (pin)B R SiMe2Ph Pd(0)L_n R₁ R₂ Pd L Si B(pin) Cl L₂Pd Si B(pin) Cl Pd (pin)B R₁ R₂ SiMe₂Cl Si B Cl O O R₁ R₂ SiMe2Cl (pin)B R₁ R₂ I Oxidative addition II Coordination of enyne III Insertion of enyne IV Reductive elimination

The
boron
and
silicon
groups
added
in
this
silaboration
reaction
are
of
great
interest
 in
 total
 synthesis
 for
 example.
 Indeed,
 the
 boronic
 ester
 can
 undergo
 Suzuki‐Miyaura
 coupling
as
previously
mentioned.
Then,
the
silicon
group
can
be
exchanged
to
another
 carbon
 group
 by
 silver(I)
 oxide
 activated
 cross‐coupling
 of
 the
 target
 molecule
 with
 a
 vinyl
 iodide
 in
 the
 presence
 of
 palladium
 catalyst
 (Scheme
 4).
 This
 method
 makes
 accessible
a
variety
of
highly
substituted
dienes
as
will
be
shown
later
on
in
this
report.
 The
 enyne
 starting
 materials
 have
 all
 been
 made
 from
 the
 corresponding
 alkyne
 and
 vinyl
bromide
via
Sonogashira
coupling.
 
 Scheme
4
Silaboration
of
enynes
followed
by
Suzuki­Miyaura
coupling
and
silver(I)
oxide
activated
cross­ coupling8_. 
 
 



 During
 the
 first
 two
 months
 of
 the
 internship,
 the
 laboratory
 work
 that
 was
 done
 dealt
 with
 another
 type
 of
 silaboration:
 addition
 of
 aldehyde
 into
 silaboration
 of
 1,3‐ enynes
(Scheme
6).
The
starting
idea
was
the
work
of
Suginome
et
al.14_{on
the
addition} of
aldehyde
in
a
silaboration
reaction
(Scheme
5).
 
 
 
 Scheme
5
Silaboration
followed
by
addition
of
aldehyde,
and
silaboration
in
presence
of
aldehyde.14 
 If
the
aldehyde
is
introduced
after
the
silaboration
step,
the
alkylborane
adds
to
the
 aldehyde
and
after
rearrangement
boron
will
be
lost.
On
the
other
hand,
if
the
aldehyde
 is
 introduced
 initially,
 a
 completely
 different
 compound
 is
 formed:
 the
 palladium
 intermediate
is
trapped
by
the
aldehyde.

 
 
 
 
 
 
 
 
 
 R1 R2 R1

(pin)B SiMe2OiPr R2 R1 R3 SiMe2OH R2 R3Br/Pd(PPh3)4/base Toluene/EtOH/H2O R1 R3 R4 R2 R4I/Ag2O Pd(PPh3)4 THF Pd/SiB Toluene PhMe2Si B O O Me Me _{Pt cat.} Me PhMe2Si B(pin) PhCHO OH Ph Me PhMe2Si Me Me Pt cat., PhCHO Ph Me Me (pin)B PhMe2SiO

The
 desired
 product
 is
 illustrated
 in
 Scheme
 6
 for
 a
 terminal
 1,3‐enyne
 with
 a
 trimethylsilyl
group
on
the
alkyne
moiety.
As
we
soon
discovered,
the
desired
reaction
 does
 not
 seem
 achievable
 at
 the
 moment
 and
 the
 focus
 of
 the
 research
 was
 switched
 from
this
topic
to
the
applications
of
silaboration
of
1,3‐enynes
(Scheme
4).








Scheme
6
Silaboration
with
small
R
group
(R=TMS)
resulting
in
1,4
addition.



 The
aim
of
this
report
is
to
present
a
new
method
to
synthesize
highly
functionalized
 dienes
 in
 the
 previously
 mentioned
 way:
 Sonogashira
 coupling,
 then
 silaboration
 followed
by
Suzuki‐Miyaura
coupling
and
finally
silver(I)
oxide
activated
cross‐coupling.
 Si OSiMe2Ph(Cl) Si Ph * B O O Si B O O Si Cl B O O O Ph H Pd or Pt

2.
Results
and
discussion



 A
‐
Sonogashira
coupling
 
 Both
1,3‐enynes
used
in
this
work
have
been
made
via
Sonogashira
coupling
(Scheme
 7)
between
an
alkyne
and
a
bromoalkene
in
presence
of
tetrakis(triphenylphosphine)‐ palladium(0),
copper(I)
iodide
and
triethylamine.
 
 
 Scheme
7
Sonogashira
coupling
between
an
alkyne
and
a
bromoalkene.
 Table
1
shows
the
results
for
the
two
coupling
reactions.
They
proceeded
as
expected
 in
good
yields
and
NMR
analysis
even
showed
that
no
purification
was
needed.
 


Table
1
Results
for
Sonogashira
coupling
(R1
and
R2
can
be
seen
in
Scheme
7).



 
 
 B
‐
Silaboration
 
 
 
 
 a)
Silaboration
of
1,3‐enynes
in
presence
of
benzaldehyde
 
 As
previously
mentioned,
this
work
was
initially
focused
on
silaboration
reactions
in
 the
 presence
 of
 benzaldehyde.
 Several
 different
 catalytic
 systems
 were
 tested
 for
 this
 purpose.
Table
2
illustrates
the
disappointing
results,
where
R1
and
R2
can
be
seen
on


Scheme
8.
Indeed,
the
desired
reaction
could
not
be
performed.





Scheme
8
Silaboration
of
1,3­enynes
in
presence
of
benzaldehyde
(where
R1
and
R2
vary
in
Table
1).



 R1 R2 R1 _{Br R} 2 Pd(PPh3)4/CuI Et3N R₁ R₂ O H Ph Pd/SiB Toluene R₁ * B OSiMe₂Ph(Cl) Ph R₂


 Table
2
Silaboration
of
enynes
in
presence
of
benzaldehyde
(*full
conversion)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


The
 starting
 point
 of
 these
 experiments
 was
 to
 perform
 work
 analogous
 to
 that
 of
 Suginome
et
al.,
which
is
described
in
Scheme
5.
The
goal
was
to
achieve
this
reaction
 with
 enynes
 as
 starting
 material
 instead
 of
 dienes
 as
 was
 the
 case
 in
 the
 reported
 study14_{.
Entries
1‐3
were
the
first
attempt,
where
standard
silaboration
conditions
were}

tested15_{.
 Both
 Pd
 and
 Pt
 complexes
 were
 tested
 as
 catalysts
 and
 the
 two
 silylboranes}

used
 by
 this
 group
 were
 used:
 the
 less
 reactive
 PhMe2SiB(pin)
 and
 the
 much
 more


reactive
ClMe2SiB(pin).
All
three
of
these
reactions
resulted
in
1,2‐addition
of
silicon
and


boron
 across
 the
 triple
 bond
 of
 the
 enyne,
 which
 is
 exactly
 the
 same
 product
 as
 silaboration
 without
 aldehyde.
 It
 might
 be
 relevant
 to
 note
 that
 there
 was
 some
 difference
between
the
two
catalysts:
platinum
allowed
full
conversion
for
this
reaction,
 whereas
palladium
did
not
for
PhMe2SiB(pin)
(Entries
2‐3).


Since
 this
 work
 was
 about
 adapting
 Suginome's
 work
 to
 enynes,
 the
 described
 catalyst
Pt(CH2=CH2)(PPh3)2
was
also
tested14
(Entry
4).
The
reaction
also
reached
full


conversion
 but
 again
 the
 presence
 of
 aldehyde
 did
 not
 result
 in
 any
 new
 product
 but
 instead
the
regular
1,2‐addition
that
is
expected
in
this
case
for
regular
silaboration15_.

A
 study
 made
 by
 this
 group16_{successively
 used
 Pd‐PEPPSI‐IPr
 as
 catalyst
 for
 the}

silaboration
 of
 1,6‐enynes.
 The
 same
 catalytic
 system
 was
 used
 with
 the
 additional
 aldehyde
but
resulted
in
no
reaction
(Entry
5).


According
to
a
recent
study
on
silaborations17_{,
a
catalytic
system
involving
nickel
was}

used
for
silaboration
of
dienes
in
the
presence
of
aldehyde.
This
system
was
also
utilized
 with
an
enyne
but
yielded
no
reaction
(Entry
6).


In
 the
 two
 last
 attempts
 with
 the
 same
 1,3‐enyne
 as
 starting
 material,
 triethylphosphine
 was
 tried
 as
 ligand
 and
 the
 two
 different
 silylboranes
 were
 used
 (Entries
 7‐8).
 Triethylphosphine
 is
 much
 less
 bulky
 than
 the
 chiral
 phosphine
 used
 in
 the
 previous
 experiment
 and
 could
 therefore
 help
 a
 reaction
 to
 occur.
 When
 using
 ClMe2SiB(pin),
 no
 reaction
 happened.
 On
 the
 other
 hand,
 when
 the
 less
 reactive


PhMe2SiB(pin)
 was
 tested,
 a
 new
 product
 was
 formed.
 The
 silylborane
 showed
 to
 be
 unreactive
enough
and
hydroacylation
of
the
triple
bond
occurred
(Scheme
9).
 
 Scheme
9
Hydroacylation
of
the
triple
bond
on
the
1,3­enyne
 After
this
extensive
search
of
conditions
that
allowed
some
of
the
wanted
product
to
 be
formed
and
the
numerous
disappointing
results,
another
theory
was
then
tested:
the
 reaction
 may
 be
 very
 substrate
 dependent.
 Two
 other
 enynes
 were
 subjected
 to
 conditions
 employed
 earlier
 but
 again
 no
 desired
 product
 was
 formed.
 Instead,
 the
 expected
product
for
the
reaction
without
aldehyde
was
afforded
(Entries
9‐11).






 
 b)
Silaboration
of
dienes
in
presence
of
benzaldehyde





None
of
the
tested
conditions
worked
in
the
expected
way,
so
the
focus
was
switched
 from
 enynes
 to
 cyclic
 dienes
 as
 starting
 material.
 Scheme
 10
 illustrates
 the
 reactions
 that
were
carried
out.
 
 
 
 Scheme
10
Silaboration
of
dienes
in
presence
of
benzaldehyde
and
the
desired
products.
 Table
3
lists
the
results
of
these
experiments
with
the
different
starting
materials,
 catalysts
and
ligands.
 
 Table
3
Results
for
silaboration
of
dienes
in
presence
of
benzaldehyde
 Bu O Ph Me Me Ph Me Me (pin)B PhMe₂SiO Cat./SiB Toluene O H Ph (pin)B Ph PhMe₂SiO (pin)B Ph PhMe2SiO ---

---We
first
put
Suginome's
results14_{to
the
test
to
make
sure
of
its
accuracy.
The
desired}

product
 was
 afforded
 in
 good
 yield
 (Entry
 1).
 With
 these
 results
 in
 hand,
 the
 same
 reaction
 was
 tested
 with
 two
 cyclic
 dienes:
 cyclopentadiene
 and
 cyclohexadiene.
 By
 using
the
same
catalyst
as
Suginome
on
cyclohexadiene,
no
reaction
occurred
(Entry
3).
 When
 using
 platinum
 together
 with
 triethylphosphine
 for
 the
 two
 dienes,
 only
 byproducts
were
formed
(Entries
2
and
4).
 Finally,
nickel
was
also
tested
as
catalyst
for
the
cyclic
dienes
(Entries
5‐6)
but
once
 again
no
reaction
occurred.
 
 
 
 c)
Silaboration
of
1,3‐enynes
 


In
 view
 of
 the
 amount
 of
 disappointing
 results
 and
 the
 fact
 that
 the
 reaction
 combining
 an
 aldehyde
 with
 silaboration
could
 not
 be
 achieved
 with
 these
 substrates,
 the
goal
of
the
project
was
completely
changed.
Instead
of
developing
a
new
reaction,
we
 tried
 to
 find
 applications
 for
 the
 silaboration
 used
 in
 this
 group
 by
 further
 transformation.
The
aim
was
to
afford
highly
substituted
dienes.
The
synthetic
pathway
 is
shown
in
Scheme
11.
 
 
 Scheme
11
Silaboration
of
enynes
followed
by
Suzuki­Miyaura
coupling
and
silver(I)
oxide
activated
cross­ coupling8_. The
first
step
is
a
Sonogashira
coupling
reaction
that
has
already
been
discussed.
In
 light
of
the
challenges
in
the
following
reactions,
only
one
standard
enyne
was
chosen
 for
 this
 work.
 The
 reaction
 sequence
 is
 not
 believed
 to
 be
 much
 affected
 by
 the
 substitution
on
the
enynes,
as
long
as
similar
functional
groups
are
used.
The
following
 steps
 are
 a
 silaboration
 reaction,
 a
 Suzuki‐Miyaura
 coupling
 and
 a
 silver(I)
 oxide
 activated
cross‐coupling.
Scheme
12
illustrates
the
silaboration
reaction
performed
on
 the
chosen
1,3‐enyne.
 
 
 
 Scheme
12
Silaboration
of

the
1,3­enyne.
 Bu Bu

(pin)B SiMe2OiPr

Bu R1 SiMe2OH R1Br/Pd(PPh3)4/base Bu R1 R2 R2I/Ag2O Pd(PPh3)4 THF Pd/SiB Toluene Bu Br Pd(PPh3)4/CuI Et3N Toluene/EtOH/H2O Bu Bu

(pin)B SiMe2OiPr

Pd/SiB Toluene




As
 this
 group
 had
 already
 discovered,
 the
 silaboration
 step
 is
 very
 smooth
 for
 this
 standard
enyne
and
the
desired
product
is
afforded
in
moderate
yields
(60‐70%).
This
 was
 the
 case
 for
 a
 small‐scale
 reaction.
 Some
 problems
 were
 encountered
 as
 this
 reaction
 was
 scaled
 up.
 When
 using
 three
 times
 the
 amount
 of
 starting
 material,
 the
 yield
dropped
to
about
20%.
This
is
believed
to
be
caused
by
the
exothermic
reaction
of
 reducing
the
Pd(II)
catalyst
to
Pd(0)
when
adding
DIBAL‐H.
This
addition
is
performed
 at
‐35
°C
and
when
the
reaction
volume
is
increased,
the
amount
of
heat
is
increased
and
 the
 heat
 diffusion
 is
 less
 efficient.
 Making
 several
 small‐scale
 reactions
 in
 parallel
 and
 combining
them
for
purification
could
easily
resolve
this
problem.






 B)
Suzuki‐Miyaura
cross‐coupling





With
 the
 product
 from
 the
 silaboration
 in
 hand,
 it
 was
 time
 for
 the
 next
 transformation
via
Suzuki‐Miyaura
coupling
(Scheme
13).
 
 
 Scheme
13
Suzuki­Miyaura
cross­coupling
of
the
silylborane.
 A
two‐phase
system
was
used
here
since
the
product
is
soluble
in
the
organic
phase
 but
the
presence
of
water
allows
for
the
transformation
of
OiPr
to
OH
function
on
the
 silicon
 atom.
 Ethanol
 is
 also
 used
 as
 solvent
 to
 enhance
 the
 exchange
 between
 both
 phases.
 The
 base
 acts
 as
 a
 simple
 activator
 for
 this
 reaction
 by
 making
 the
 transmetallation
step
faster5_{.
According
to
Suzuki
et
al.,
the
base
coordinates
to
boron} facilitating
the
transmetallation.
Table
4
shows
the
results
in
this
step
with
each
product
 and
its
isolated
yield.
 
 Table
4
Results
for
Suzuki­Miyaura
cross­coupling
 
 


The
 first
 problem
 that
 we
 faced
 during
 this
 step
 is
 the
 unreactivity
 of
 the
 halogen
 reagent.
 Indeed
 during
 every
 reaction
 of
 this
 type
 that
 was
 performed,
 the
 major
 product
was
the
coupling
product
but
there
was
always
a
minor
product
present,
which
 was
from
reduction
on
the
carbon
with
boron
attached
on
it.
In
other
words,
the
minor


Bu

(pin)B SiMe₂OiPr

Bu

R₃ SiMe₂OH

Toluene/EtOH/H₂O R₃Br/Pd(PPh₃)₄/base

product
 had
 its
 boron
 group
 exchanged
 to
 hydrogen.
 The
 formation
 of
 this
 protodeborylation
 product
 was
 not
 negligible
 since
 it
 made
 up
 30‐50%
 of
 the
 final
 mixture.
This
problem
was
not
solved
because
of
the
lack
of
time
for
this
project.
On
the
 other
 hand,
 it
 opened
 the
 door
 to
 a
 new
 possibility:
 to
 selectively
 functionalize
 the
 dienes.
Indeed,
by
this
method
it
would
be
possible
to
add
functional
group
on
certain
 carbons
 and
 not
 necessarily
 on
 all
 of
 them.
 This
 group
 had
 not
 yet
 accomplished
 to
 selectively
remove
the
boronic
ester
although
it
is
well
established
how
to
remove
the
 silicon
 moiety18_{.
 By
 using
 the
 same
 reaction
 conditions
 as
 for
 the
 Suzuki‐coupling}

described
herein
and
not
introducing
any
halogen
reagent,
this
protodeborylation
could
 be
afforded
in
quantitative
yields
(Entry
6).


A
few
attempts
were
made
to
perform
the
silaboration
and
the
Suzuki‐coupling
in
a
 one‐pot
 reaction.
 We
 hoped
 that
 this
 would
 increase
 the
 efficiency
 of
 the
 synthetic
 pathway
but
this
shortcut
was
proven
to
be
much
harder
to
take
than
anticipated.
For
an
 unknown
reason,
only
byproducts
were
formed.
The
boronic
ester
moiety
revealed
to
be
 very
 unstable
 in
 the
 presence
 of
 water
 and
 some
 self‐coupling
 was
 observed.
 What
 is
 very
 hard
 to
 understand
 is
 the
 fact
 that
 this
 does
 not
 occur
 when
 performing
 these
 reactions
in
two
different
steps.
Troubled
by
this
problem,
and
the
fact
that
even
if
this
 one‐pot
 synthesis
 could
 be
 performed
 it
 would
 not
 improve
 the
 synthesis
 in
 a
 revolutionizing
way,
we
decided
to
abandon
this
issue
and
focus
on
other
more
relevant
 problems.


We
encountered
a
final
difficulty
with
this
Suzuki‐coupling
step.
When
the
coupling
 was
performed
with
1‐iodohex‐1‐ene,
isomerization
occurred
under
certain
conditions.
 As
 Scheme
 14
 illustrates,
 two
 products
 were
 afforded
 after
 the
 reaction.
 After
 some
 optimization
 of
 the
 conditions
 for
 this
 particular
 substrate,
 only
 the
 wanted
 isomer
 could
be
afforded,
which
can
be
seen
on
the
left
side
of
Scheme
14.








Scheme
14
Two
isomers,
products
from
Suzuki­coupling
with
1­iodohex­1­ene


The
origin
of
this
isomerization
has
not
been
proven
in
this
study.
On
the
other
hand,
 it
 is
 obvious
 that
 for
 this
 new
 product
 to
 be
 formed,
 the
 double
 bond
 affected
 by
 this
 rotation
must
become
of
single
bond
character
in
an
intermediate
of
the
catalytic
cycle.
 A
simple
explanation
can
be
that
when
the
palladium
catalyst
coordinates
to
one
of
the
 carbons
 after
 the
 transmetallation
 step,
 it
 would
 shift
 the
 C‐C
 double
 bond
 to
 a
 Pd‐C
 double
bond
because
of
its
electronegativity.
This
issue
will
be
discussed
later
on
in
the
 report
 since
 isomerization
 was
 an
 even
 bigger
 issue
 for
 the
 silver(I)
 oxide
 activated
 cross‐coupling.


Having
 resolved
 some
 of
 the
 encountered
 problems,
 several
 silanol‐products
 were
 afforded
at
this
point.
Only
the
last
coupling
step
was
yet
to
be
done,
in
which
the
silanol
 group
is
exchanged
to
an
aromatic
ring.
 
 
 
 Bu Si OH Bu Bu Si OH Bu

D)
Silver(I)
oxide
activated
cross‐coupling
 


In
the
early
stages
of
the
internship,
silver(I)
oxide
activated
cross‐coupling
tried
to
 be
 achieved
 with
 some
 vinyl
 iodides
 or
 alkyne
 iodides
 but
 the
 reactions
 could
 not
 be
 performed
 because
 of
 the
 unreactivity
 of
 the
 halogen.
 With
 that
 in
 mind,
 we
 decided
 instead
to
couple
the
silanols
with
different
aryl
iodides,
which
are
much
more
reactive.


In
this
coupling
reaction,
both
Pd(PPh3)4
and
silver(I)
oxide
play
an
important
role.
In


the
described
catalytic
system
by
Hiyama
et
al.19_{,
the
aromatic
group
and
the
iodine
get}

coordinated
 to
 the
 palladium
 catalyst
 in
 an
 oxidative
 addition.
 As
 the
 substrate
 is
 approaching
the
coordinated
catalyst,
silver(I)
oxide
helps
stabilize
the
transition
state.
 The
 suggested
 six‐membered
 transition
 state19_{is
 illustrated
 in
 Scheme
 15.
 The}

procedure
 that
 has
 been
 employed
 for
 these
 couplings
 had
 already
 been
 used
 by
 the
 group
for
some
time
and
was
not
further
optimized
for
all
compounds.








Scheme
15
Proposed
mechanism
for
silver(I)
oxide
activated
coupling19_.

A
 great
 problem
 was
 faced
 at
 this
 point.
 Indeed,
 when
 vinyl
 bromide
 was
 coupled
 with
the
diene
in
the
Suzuki‐coupling,
two
isomers
were
afforded
in
the
silver(I)
oxide
 activated
coupling
(Scheme
16).



 


Scheme
16
Structure
of
the
two
isomers
afforded.


We
have
understood
that
a
rotation
happens
around
the
functionalized
double
bond.
 This
 phenomenon
 has
 not
 been
 proven
 at
 this
 point
 but
 as
 was
 the
 case
 before,
 this
 double
bond
must
probably
become
of
single
bond
character
in
an
intermediate
to
be
 able
 to
 turn.
 According
 to
 one
 of
 several
 reports
 on
 this
 topic20_{,
 the
 proposed}

mechanism
for
this
transformation
is
described
in
Scheme
17.
 






Scheme
17
Proposed
mechanism
for
isomerization20_.

After
 the
 transmetallation
 step
 in
 the
 catalytic
 cycle,
 palladium
 finds
 itself
 coordinated
to
both
the
diene
and
the
aromatic
group
that
is
supposed
to
take
the
place
 of
silicon.
It
is
possible
that
the
electronegativity
of
palladium
drives
the
electron
density
 away
from
the
existing
double
bond
and
thereby
shifting
its
position
(Scheme
17).
If
this
 Aryl Pd I Ag R Si O Ag Bu R Bu R Ph Ph Bu Si OH R _ArPdIL 2 Bu PdArL2 R PdArL2 R Bu Bu PdArL2 R PdArL2 R Bu 1 2

would
 happen,
 then
 a
 new
 equilibrium
 would
 appear
 since
 the
 newly
 formed
 single
 bond
would
be
able
to
rotate
and
thus
resulting
in
the
formation
of
compound
2.





Scheme
18
Further
stabilization
of
the
intermidiate21_.

Another
 much
 older
 article21_{reports
 that,
 in
 some
 cases
 when
 free}

triphenylphosphine
 is
 present
 in
 the
 reaction
 mixture,
 the
 phosphine
 could
 help
 stabilize
the
discussed
intermediate.
Indeed,
the
phosphine
could
add
to
the
positively
 charged
carbon
and
thereby
stabilizing
the
charge
distribution
(Scheme
18).
Since
the
 catalyst
used
for
this
reaction
is
Pd(PPh3)4,
free
triphenylphosphine
has
to
be
present
in


the
reaction
mixture.


Without
 being
 able
 to
 confirm
 any
 of
 these
 explanations
 to
 the
 observed
 isomerization
yet,
it
stays
hypothetical
and
waiting
to
be
proven.


Table
 5
 lists
 the
 actual
 results
 for
 the
 silver(I)
 oxide
 activated
 cross‐coupling.
 The
 very
 large
 discrepancy
 in
 isolated
 yields
 for
 the
 different
 compounds
 has
 a
 simple
 explanation:
 some
 compounds
 with
 high
 polarity
 are
 quite
 hard
 to
 purify
 by
 flash
 column
 chromatography
 since
 they
 have
 large
 attractive
 interactions
 with
 silica.
 The
 actual
yields
before
purification
would
therefore
be
much
higher.
 
 Table
5
Final
products
for
the
silver(I)
oxide
activated
cross­coupling
 
 
 PdArL₂ R Ph₃P Bu

The
 cis/trans
 ratios
 were
 calculated
 by
1_{H
 NMR
 analysis
 of
 the
 crude
 reaction}

mixture.
 The
 first
 observation
 that
 can
 be
 made
 from
 this
 set
 of
 data
 is
 that
 the
 isomerization
 is
 very
 substrate
 dependent.
 For
 some
 molecules,
 no
 isomerization
 was
 observed
at
all
(entries
7,
8‐12,
and
14).
This
can
be
quite
complex
to
understand
and
 explain.


For
 one
 of
 the
 substrates,
 all
 couplings
 resulted
 in
 isomerization
 to
 some
 extent
 (entries
1‐3).
Here
again,
it
is
difficult
to
understand
why
this
compound
gave
rise
to
this
 phenomenon
and
another
substrate
did
not
but
the
difference
in
different
couplings
for
 the
 same
 starting
 material
 is
 interesting.
 For
 entry
 1,
 where
 an
 electron‐withdrawing
 group
 is
 present
 on
 the
 aromatic
 ring,
 more
 isomerization
 is
 observed
 compared
 to
 entry
 2.
 This
 is
 also
 the
 case
 for
 entries
 5‐6.
 These
 observations
 strengthen
 the
 hypothesis
made
earlier
for
the
mechanism
of
isomerization
(Scheme
17).
An
electron‐ withdrawing
group
bonded
to
the
palladium
in
the
intermediate
would
promote
shifting
 of
the
double
bond
from
carbon‐carbon
to
carbon‐palladium.
By
further
stabilization
of
 this
 intermediate,
 it
 would
 give
 more
 time
 for
 the
 single
 bond
 to
 turn
 and
 thereby
 resulting
in
larger
amount
of
trans‐product.


For
 one
 of
 the
 compounds,
 only
 one
 coupling
 was
 made
 (entry
 13).
 The
 yield
 was
 very
 high
 for
 this
 compound
 but
 the
 two
 isomers
 were
 afforded
 in
 almost
 equal
 quantities.
This
may
be
explained
by
the
substrate‐dependency
of
this
reaction.
What
is
 most
interesting
in
this
case
is
that
a
heavily
substituted
dienyne
is
produced.
A
possible
 next
step
for
this
compound
could
be
to
start
the
whole
synthesis
from
the
beginning
 with
a
silaboration
of
the
triple
bond
and
hypothetically
resulting
in
a
heavy
substituted
 triene.


A
 few
 attempts
 were
 performed
 in
 the
 end
 of
 this
 project
 to
 try
 to
 resolve
 the
 isomerization
 problem.
 One
 theory
 was
 that
 the
 extra
 addition
 of
 a
 fluorine
 activator
 would
be
beneficial.
According
to
a
recent
study
by
Whittaker
et
al.22_{,
by
activating
the} carbon‐silicon
bond
with
fluorine,
coupling
would
occur
much
easier.
Unfortunately,
the
 activation
of
the
carbon‐silicon
bond
was
not
successful
for
this
compound.
The
reaction
 gave
a
major
unknown
product
and
several
byproducts.
 Even
if
this
isomerization
seems
very
hard
to
control,
one
last
attempt
was
made
to
 try
to
understand
its
origin.
According
to
a
paper
by
Lipshutz
et
al.23_{,
the
choice
of
ligand} and
catalyst
has
a
great
impact
on
the
stereochemical
outcome
in
coupling
reactions.
A
 few
tests
with
different
catalysts
and
ligands
were
carried
out
but
they
all
resulted
in
no
 reaction
after
2
days.
TLC
analysis
seemed
to
point
to
a
very
small
amount
of
wanted
 product
but
1_{H
NMR
analysis
could
not
prove
its
presence.
We
were
therefore
not
able} to
study
the
amount
of
isomerization
that
occurred.
The
silver(I)
oxide
activated
cross‐ coupling
of
these
compounds
seems
to
need
the
presence
of
Pd(PPh3)4
as
catalyst.
 
 


3.
Conclusion





This
 study
 shows
 a
 new
 synthetic
 approach
 to
 highly
 functionalized
 dienes.
 The
 majority
 of
 the
 compounds
 were
 obtained
 as
 pure
 substances
 in
 moderate
 to
 good
 overall
 yields
 (20‐55%
 over
 4
 steps)
 from
 commercially
 available
 and
 cheap
 starting
 materials.
 This
 synthesis
 starts
 with
 a
 simple
 Sonogashira
 coupling
 between
 a
 substituted
alkyne
and
a
bromoalkene
to
afford
an
enyne.
The
next
step
is
a
silaboration
 of
the
enyne
resulting
in
addition
of
a
boronic
ester
and
a
silyl
group
to
the
triple
bond.
 The
newly
formed
diene
is
then
subjected
to
a
Suzuki‐Miyaura
coupling
to
replace
the
 boronic
ester
with
a
large
substituent.
Finally,
a
silver(I)
oxide
activated
cross‐coupling
 allows
the
exchange
of
the
silyl
moiety
to
an
aromatic
group.
This
last
step
is
somewhat
 challenging
 since
 its
 outcome
 is
 very
 substrate
 dependent.
 For
 some
 molecules,
 isomerization
occurs
around
the
double
bond
with
the
two
added
functionalities.


A
 bromoalkyne
 was
 also
 used
 in
 the
 Suzuki
 coupling
 thus
 hypothetically
 allowing
 further
functionalization.


This
 method
 could
 be
 of
 great
 importance
 in
 the
 field
 of
 total
 synthesis
to
 produce
 pharmaceutical
 drugs.
 Indeed,
 several
 compounds
 on
 the
 market
 are
 made
 of
 these
 highly
 functionalized
 double
 bonds
 and
 dienes
 can
 easily
 be
 transformed
 by
 powerful
 reactions
such
as
the
Diels‐Alder
reaction24_{.
Silicon
and
boron
are
both
quite
cheap
and}

less
 toxic
 than
 the
 other
 alternatives
 in
 coupling
 reactions5,7_{,
 which
 make
 them
 viable}

candidates
for
the
future
of
organometallic
chemistry.
 
 
 





Acknowledgments


I
 want
 to
 thank
 my
 supervisor
 and
 tutor
 during
 this
 diploma
 work
 as
 well
 as
 my
 colleagues
in
the
laboratory,
especially
Professor
Christina
Moberg
for
welcoming
me
in
 the
research
group,
for
the
help
and
talented
guidance
through
this
project,
and
for
the
 inspiring
 discussions
 we
 have
 had
 about
 organic
 chemistry.
 I
 also
 want
 to
 thank
 my
 tutor
Doctor
Hui
Zhou
for
his
help
in
the
laboratory
and
the
deep
conversations
we
have
 had
on
both
our
research
projects.
Finally
I
would
like
to
thank
Robin
Hertzberg
for
his
 help
in
the
early
stages
of
the
project,
Inanllely
Gonzalez
for
her
cheerfulness
every
day
 in
the
laboratory,
Brinton
Seashore‐Ludlow
for
taking
on
the
task
of
being
my
opponent,
 and
all
other
researchers
at
Organic
Chemistry
for
creating
a
productive
and
enjoyable
 working
environment.


Experimental
Section


General
Experimental
Procedure


1_{H
NMR
experiments
were
run
on
either
400MHz
Bruker
Advance
400
or
500
MHz}

DMX
500
instruments.
All
products
were
dissolved
in
CDCl3
and
the
solvent
peak
was


used
 as
 internal
 standard
 (CDCl3
1H
 7.26ppm).
 Chemical
 shifts
 are
 given
 in
 ppm,
 the


multiplicity
with
abbreviations
(s
=
singlet,
d
=
doublet,
dd
=
double
doublet,
t
=
triplet,
 q=
quartet,
dq
=
double
quartet,
m
=
mutliplet...),
and
coupling
constants
in
Hz.


Thin
 Layer
 Chromatography
 has
 been
 made
 on
 Sigma‐Aldrich
 silica
 gel
 F254
 plates.


Phosphomolybdic
 acid
 (PMA)
 was
 used
 as
 staining
 solution
 for
 developing
 the
 TLC
 plates
after
exposing
them
to
UV‐light.


Moisture
 and
 air‐sensitive
 reactions
 were
 performed
 in
 oven‐dried
 glassware
 and
 under
 nitrogen
 atmosphere.
 All
 silaborations
 and
 coupling
 reactions
 were
 prepared
 inside
 a
 nitrogen‐filled
 glovebox
 and
 if
 heating
 was
 necessary,
 the
 latter
 was
 done
 outside
using
a
tightly
closed
vial.


A
‐
Synthesis
of
enynes


(Z)­Non­2­en­4­yne.
 To
 a
 solution
 of
 cis‐1‐bromo‐1‐propene
 (360
 mg,
 3
 mmol),


Pd(PPh3)4
(10.4
mg,
0.009
mmol,
0.3
mol%),
and
copper(I)
iodide
(11.4
mg,
0.06
mmol,


2
 mol%)
 in
 1.5
 mL
 of
 Et2NH,
 cooled
 in
 an
 ice‐bath,
 was
 added
 1‐hexyne
 (345
 µL,
 3


mmol).
 Then
 the
 temperature
 was
 raised
 to
 room
 temperature
 and
 a
 solid
 formed
 gradually.
After
stirring
for
4.5
hours,
the
reaction
mixture
was
diluted
with
hexane
and
 filtered
 through
 a
 short
 celite
 plug,
 and
 the
 filter
 cake
 was
 washed
 with
 hexane.
 2M
 hydrochloric
acid
was
added
to
the
resulting
hexane
solution
in
an
ice‐bath
to
remove
 diethylamine.
 The
 organic
 layer
 was
 washed
 with
 saturated
 aqueous
 ammonium
 chloride
and
water.
After
drying
over
magnesium
sulphate,
the
solvent
was
evaporated
 under
reduced
pressure
to
afford
307
mg
(84%)
of
a
colorless
liquid.
1_{H
NMR
(500
MHz,} CDCl3)
δ
=
5.88
(dq,
J
=
6.8,
10.5,
1H),
5.46
(dq,
J
=
1.6,
10.5,
1H),
2.37‐2.34
(m,
2H),
1.85
 (dd,
J
=
6.8,
1.5,
3H),
1.55‐1.42
(m,
4H),
0.93
(t,
J
=
7.4,
3H).
 Oct­1­en­3­yne.
To
a
solution
of
vinyl
bromide
(3
mL,
1M
in
THF,
3
mmol),
Pd(PPh3)4
 (10.4
mg,
0.009
mmol,
0.3
mol%),
and
copper(I)
iodide
(11.4
mg,
0.06
mmol,
2
mol%)
in
 1.5
mL
of
Et2NH,
cooled
in
an
ice‐bath,
was
added
1‐hexyne
(345
µL,
3
mmol).
Then
the


temperature
 was
 raised
 to
 room
 temperature
 and
 a
 solid
 formed
 gradually.
 After
 stirring
 for
 3.5
 hours,
 the
 reaction
 mixture
 was
 poured
 into
 approximately
 10
 mL
 of
 water
at
0
°C.
The
aqueous
mixture
was
extracted
with
diethyl
ether,
and
the
combined
 organic
 fractions
 were
 washed
 with
 2
 M
 hydrochloric
 acid
 solution
 and
 finally
 dried
 over
 magnesium
 sulphate.
 The
 solvent
 was
 evaporated
 under
 reduced
 pressure
 to
 afford
237
mg
(73%)
of
a
yellow
oil.
1_{H
NMR
(500
MHz,
CDCl3)
δ
=
5.78
(ddt,
1H,
J
=
17.4,}

10.9,
1.9),
5.54
(ddt,
1H,
J
=
17.4,
2.5,
0.6),
5.37
(dd,
1H,
J
=
11.0,
2.5),
2.31
(m,
2H),
1.53‐ 1.40
(m,
4H),
0.92
(t,
3H,
J
=
7.4).



 
 B
­
Synthesis
of
silylborane
starting
material
 
 
 
 Procedure
according
to
Organometallics
2000,
19,
4647‐4649.
 Dimethyl(phenyl)(4,4,5,5­tetramethyl­1,3,2­dioxaborolan­2­yl)silane.
Lithium
(0.4
 g,
62
mmol,
4
eq.)
was
introduced
into
a
flask.
After
repetitive
flushing
with
argon
and
 vacuum,
 chlorodimethyl(phenyl)silane
 (2.6
 mL,
 15.5
 mmol)
 was
 added
 with
 15
 mL
 of
 dry
 THF.
 The
 mixture
 was
 stirred
 at
 room
 temperature
 overnight.
 The
 crude
 was
 transferred
 under
 argon
 into
 a
 funnel
 for
 filtration.
 2‐isopropoxy‐4,4,5,5‐tetramethyl‐ 1,3,2‐dioxaborolane
(5
mL)
was
added
into
another
flask
with
15
mL
of
dry
hexane.
The
 newly
 formed
 (dimethyl(phenyl)silyl)lithium
 was
 added
 dropwise
 over
 30
 minutes
 at



 0
°C
under
argon.
The
reaction
mixture
was
stirred
at
room
temperature
overnight.
The
 solvents
were
then
evaporated
under
vacuum
to
give
a
white
residual
solid.
The
product
 was
 taken
 up
 by
 hexane
 to
 remove
 insoluble
 substances.
 It
 was
 then
 filtrated
 under
 argon
 and
 distilled
 to
 afford
 1.9
 g
 (47%)
 of
 the
 desired
 product.
1_{H NMR (500 MHz,}

CDCl3) δ = 7.60 (d, J=2.0 Hz, 2H), 7.35 (dd, J=3.2 & 2.0 Hz, 3H), 1.27 (s, 12H), 0.36 (s, 6H).
 
 
 Procedure
according
to
Organometallics
2007,
26,
1291‐1294.
 chlorodimethyl(4,4,5,5­tetramethyl­1,3,2­dioxaborolan­2­yl)silane.
 Dimethylphenylsilylpinacolborane
(3.95
g,
15.1
mmol)
was
put
in
a
flask
with
benzene
 (20
mL).
Aluminum
chloride
(201
g,
1.51
mmol)
was
added
and
the
mixture
was
stirred
 at
 room
 temperature.
 Upon
 dissolution
 of
 the
 aluminum
 chloride
 and
 the
 mixture
 showing
 a
 pale
 yellow
 color,
 hydrogen
 chloride
 was
 passed
 through
 the
 reaction
 mixture
via
a
tube
with
intense
stirring.
The
reaction
was
followed
by
NMR.
Upon
full
 conversion,
the
product
was
transferred
into
a
funnel
and
filtrated
through
a
short
silica
 plug
 under
 argon
 atmosphere.
 Benzene
 was
 then
 removed
 under
 reduced
 pressure
 to
 afford
1.83
g
(55%)
of
the
desired
compound.
1_{H NMR (500 MHz, CDCl} 3) δ = 1.27 (s, 12H), 0.52 (s, 6H).
 Si B O O Si B Cl O O

C
­
Silaboration
in
presence
of
benzaldehyde



 1.
Enynes








Inside
a
nitrogen‐filled
glovebox,
Pd(acac)2
(6.0
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (phenyldimethylsilyl)pinacolborane
(52
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(24
mg,
0.2
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
heated
to
80
°C
and
stirred
for
24
hours.
After
removal
of
 solvents
with
a
rotary
evaporator,
an
NMR
analysis
showed
that
the
wrong
product
was
 formed
 (addition
 of
 Si
 and
 B
 to
 the
 triple
 bond).
 The
 latter
 was
 still
 isolated
 by
 flash
 column
chromatography
(hexane/DCM
5:1)
to
make
sure
that
this
hypothesis
was
right.
 





Inside
a
nitrogen‐filled
glovebox,
Pd(acac)2
(6.0
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (chlorodimethylsilyl)pinacolborane
(44
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(24
mg,
0.2
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
stirred
at
room
temperature
for
24
hours.
Pyridine
(32.2
 µL,
0.4
mmol)
and
iPrOH
(30.6
µL,
0.4
mmol)
were
then
added
to
the
crude
and
stirred
 for
 another
 12
 hours.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
the
wrong
product
was
formed
(addition
of
Si
and
B
to
the
triple
 bond).









Inside
a
nitrogen‐filled
glovebox,
Pt(acac)2
(7.9
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (phenyldimethylsilyl)pinacolborane
(52
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(24
mg,
0.2
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
heated
to
80
°C
and
stirred
for
24
hours.
After
removal
of


Bu

PhMe₂SiB(pin) PhCHO

Pd(acac)₂ PEt₃ Toluene 80 °C 1,2-addition of Si and B on alkyne Bu _ClMe 2SiB(pin) PhCHO Pd(acac)₂ PEt₃ Toluene r.t. 1,2-addition of Si and B on alkyne Bu _PhMe 2SiB(pin) PhCHO Pt(acac)2 PEt₃ Toluene 80°C 1,2-addition of Si and B on alkyne But full conversion of SiB

solvents
with
a
rotary
evaporator,
an
NMR
analysis
showed
that
the
wrong
product
was
 formed
(addition
of
Si
and
B
to
the
triple
bond).
On
the
other
hand,
no
starting
material
 was
left
in
the
mixture.








Inside
 a
 nitrogen‐filled
 glovebox,
 Pt(CH2=CH2)2(PPh3)2
 (5.8
 mg,
 2
 mol%)
 and
 hexane


(0.1
 mL)
 were
 put
 in
 a
 vial.
 (Phenyldimethylsilyl)pinacolborane
 (103
 mg,
 0.39
 mmol),
 (Z)‐non‐2‐en‐4‐yne
 (133
 mg,
 0.59
 mmol),
 and
 benzaldehyde
 (120
 µL,
1.2
mmol)
were
 sequentially
 added
 to
 the
 solution
 and
 the
 resulting
 mixture
 was
 heated
 to
 80
 °C
 and
 stirred
 for
 65
 hours.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
the
wrong
product
was
once
again
formed
(addition
of
Si
and
B
to
 the
triple
bond).
On
the
other
hand,
no
starting
material
was
left
in
the
mixture.





According
to
Adv.
Synth.Catal.,
2010,
352,
2559‐2570,
Pd‐PEPPSI‐iPr
(6.8
mg,
5
mol%)
 was
 put
 in
 a
 vial
 with
 THF
 (0.2
 mL)
 inside
 a
 nitrogen‐filled
 glovebox.
 MeMgCl
 (3M
 in
 THF,
6.7
µL,
0.02
mmol)
was
then
added
at
‐35
°C
and
the
mixture
was
stirred
for
one
 hour.
 (Phenyldimethylsilyl)pinacolborane
 (52
 mg,
 0.2
 mmol),
 (Z)‐non‐2‐en‐4‐yne
 (36
 mg,
0.3
mmol),
and
benzaldehyde
(61
µL,
0.6
mmol)
were
then
sequentially
added
to
the
 solution
with
THF
(0.15
mL)
and
the
resulting
mixture
was
heated
at
55
°C
for
20
hours.
 After
 removal
 of
 solvent
 with
 rotary
 evaporator,
 an
 NMR
 analysis
 showed
 that
 no
 reaction
occurred.





According
 to
 Angewandte,
 2011,
 50,
 1‐5,
 Ni(acac)2
 (5.1
 mg,
 10
 mol%)
 and
 2,6‐

tetramethyl‐dinaphtol(1,3,2)dioxaphosphepin‐4‐amine
 (7.7
 mg,
 10
 mol%)
 were
 introduced
to
a
vial
with
DMF
(2
mL)
inside
a
nitrogen‐filled
glovebox.
DIBAL‐H
(13.3
 µL,
 10
 mol%)
 was
 then
 slowly
 added
 at
 ‐35
 °C
 and
 the
 solution
 was
 stirred
 at
 room
 temperature
 for
 15
 minutes.
 (Phenyldimethylsilyl)pinacolborane
 (130
 mg,
 0.5
 mmol),
 (Z)‐non‐2‐en‐4‐yne
(24
mg,
0.2
mmol),
and
benzaldehyde
(51
µL,
0.5
mmol)
were
then
 sequentially
 added
 to
 the
 solution
 and
 the
 resulting
 mixture
 was
 stirred
 at
 room
 temperature
 for
 20
 hours.
 After
 removal
 of
 solvent
 with
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
no
reaction
occurred.
 
 
 
 Bu _PhMe 2SiB(pin) PhCHO Hexane 80°C 1,2-addition of Si and B on alkyne Pt(CH2=CH2)(PPh3)2 But full conversion of SiB Bu _PhMe 2SiB(pin) PhCHO Pd-PEPPSI-iPr MeMgCl THF 80°C No reaction Bu

PhMe2SiB(pin) PhCHO

Ni(acac)2

carbene DMF r.t.




Inside
a
nitrogen‐filled
glovebox,
Pd(acac)2
(6.0
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (chlorodimethylsilyl)pinacolborane
(44
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(22
mg,
0.2
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
stirred
at
room
temperature
for
12
hours.
Pyridine
(32.2
 µL,
0.4
mmol)
and
iPrOH
(30.6
µL,
0.4
mmol)
were
then
added
to
the
crude
and
stirred
 for
 another
 12
 hours.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
the
wrong
product
was
formed
(addition
of
Si
and
B
to
the
triple
 bond).




 





Inside
a
nitrogen‐filled
glovebox,
Pt(acac)2
(7.9
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (chlorodimethylsilyl)pinacolborane
(44
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(22
mg,
0.2
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
stirred
at
room
temperature
for
12
hours.
Pyridine
(32.2
 µL,
0.4
mmol)
and
iPrOH
(30.6
µL,
0.4
mmol)
were
then
added
to
the
crude
and
stirred
 for
 another
 12
 hours.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
the
wrong
product
was
formed
(addition
of
Si
and
B
to
the
triple
 bond).









Inside
a
nitrogen‐filled
glovebox,
Ni(acac)2
(5.1
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (phenyldimethylsilyl)pinacolborane
(52
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(24
mg,
0.2
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
heated
to
80
°C
and
stirred
for
24
hours.
After
removal
of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
 showed
 that
 a
 new
 product
 was
 formed
 which
 was
 not
 the
 desired
 one.
 The
 latter
 was
 purified
 by
 flash
 column
 chromatography
(hexane/DCM
10:1)
to
be
able
to
identify
that
benzaldehyde
got
added
 on
the
triple
bond
and
that
the
silylborane
did
not
react
at
all.



 ClMe₂SiB(pin) PhCHO

Pd(acac)₂ PEt3 Toluene r.t. 1,2-addition of Si and B on alkyne Bu

ClMe₂SiB(pin) PhCHO

Pt(acac)₂ PEt₃ Toluene r.t. 1,2-addition of Si and B on alkyne Bu Bu _PhMe 2SiB(pin) PhCHO Ni(acac)₂ PEt3 Toluene 80°C 1-addition of PhCHO on alkyne




Inside
a
nitrogen‐filled
glovebox,
Ni(acac)2
(5.1
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (chlorodimethylsilyl)pinacolborane
(44
mg,
0.2
mmol),
(Z)‐non‐2‐en‐4‐yne
(22
mg,
0.2
 mmol),
 and
 benzaldehyde
 (20
 µL,
 0.2
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
stirred
at
room
temperature
for
65
hours.
Pyridine
(32.2
 µL,
0.4
mmol)
and
iPrOH
(30.6
µL,
0.4
mmol)
were
then
added
to
the
crude
and
stirred
 for
 another
 12
 hours.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
no
reaction
occurred.







 Inside
a
nitrogen‐filled
glovebox,
Pt(acac)2
(7.9
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
toluene
(0.5
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (phenyldimethylsilyl)pinacolborane
 (52
 mg,
 0.2
 mmol),
 but‐3‐en‐1‐yn‐1‐ yltrimethylsilane
 (25
 mg,
 0.2
 mmol),
 and
 benzaldehyde
 (20
 µL,
 0.2
 mmol)
 were
 sequentially
added
to
the
solution
and
the
resulting
mixture
was
stirred
at
80
°C
for
65
 hours.
After
removal
of
solvents
with
a
rotary
evaporator,
an
NMR
analysis
showed
that
 the
 wrong
 product
 was
 formed
 (1,4‐addition
 of
 Si
 and
 B).
 To
 be
 able
 to
 identify
 this
 product,
it
was
purified
by
flash
column
chromatography
(hexane/DCM
5:1).






 2.
Dienes



 


According
 to
 J.
 Am.
 Chem.
 Soc.
 1998,
 120,
 4248‐4249
 ,
 Pt(CH2=CH2)(PPh3)2
 (5.7
 mg,
 2


mol%)
was
introduced
into
a
vial
with
hexane
(0.1
mL)
inside
a
nitrogen‐filled
glovebox.
 (Phenyldimethylsilyl)pinacolborane
 (103
 mg,
 0.39
 mmol),
 1,3‐dimethyl‐1,3‐butadiene
 (48
 mg,
 0.59
 mmol),
 and
 benzaldehyde
 (120
 µL,
 1.2
 mmol)
 were
 then
 added
 to
 the
 solution
 and
 the
 resulting
 mixture
 was
 stirred
 at
 80
 °C
 for
 4
 hours.
 An
 NMR
 analysis
 showed
 that
 the
 desired
 product
 was
 formed
 and
 since
 this
 was
 only
 a
 test
 of
 reproducibility
of
the
paper,
the
product
was
not
purified.
 
 Bu _ClMe 2SiB(pin) PhCHO Ni(acac)₂ PEt3 Toluene r.t. No reaction Me₃Si _PhMe 2SiB(pin) PhCHO Pt(acac)₂ PEt₃ Toluene 80°C 1,4-addition (10% of 1,2-add) Ph Me Me (pin)B PhMe₂SiO Me Me




Inside
a
nitrogen‐filled
glovebox,
Pt(acac)2
(7.9
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
hexane
(0.05
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (phenyldimethylsilyl)pinacolborane
(52
mg,
0.2
mmol),
1,3‐cyclohexadiene
(24
mg,
0.3
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
the
resulting
mixture
was
heated
to
80
°C
and
stirred
for
65
hours.
After
removal
of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
 showed
 that
 only
 unknown
 undesired
products
were
formed.



 



 


Inside
 a
 nitrogen‐filled
 glovebox,
 Pt(CH2=CH2)2(PPh3)2
 (2.9
 mg,
 2
 mol%)
 and
 hexane


(0.05
 mL)
 were
 put
 in
 a
 vial.
 (Phenyldimethylsilyl)pinacolborane
 (53
 mg,
 0.2
 mmol),
 1,3‐cyclohexadiene
 (24
 mg,
 0.3
 mmol),
 and
 benzaldehyde
 (60
 µL,
 0.6
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
 the
 resulting
 mixture
 was
 heated
 to
 80
 °C
 and
 stirred
 for
 65
 hours.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
showed
that
no
reaction
occurred.





Inside
a
nitrogen‐filled
glovebox,
Pt(acac)2
(7.9
mg,
10
mol%),
PEt3
(5.8
µL,
20
mol%)


and
hexane
(0.05
mL)
were
put
in
a
vial.
DIBAL‐H
(1.5
M
in
toluene,
26.6
µL,
20
mol%)
 was
 then
 added
 at
 ‐35
 °C.
 After
 15
 minutes
 of
 stirring
 at
 room
 temperature,
 (phenyldimethylsilyl)pinacolborane
 (52
 mg,
 0.2
 mmol),
 1,3‐cyclopentadiene
 freshly
 distilled
 from
 dicyclopentadiene
 (20
 mg,
 0.3
 mmol),
 and
 benzaldehyde
 (61
 µL,
 0.6
 mmol)
were
sequentially
added
to
the
solution
and
the
resulting
mixture
was
heated
to
 80
°C
and
stirred
for
65
hours.
After
removal
of
solvents
with
a
rotary
evaporator,
an
 NMR
analysis
showed
that
only
unknown
undesired
products
were
formed.


PhMe₂SiB(pin) PhCHO

Pt(acac)₂ PEt3 Hexane 80°C Undesired biproducts

PhMe₂SiB(pin) PhCHO

Hexane 80°C

No reaction

Pt(CH2=CH2)(PPh3)2

PhMe₂SiB(pin) PhCHO

Pt(acac)₂ PEt₃ Hexane 80°C Undesired biproducts




Inside
a
nitrogen‐filled
glovebox,
Ni(cod)2
(3
mg,
10
mol%),
PPh3
(2.9
mg,
10
mol%)
and


DMF
(1
mL)
were
put
in
a
vial.
(Phenyldimethylsilyl)pinacolborane
(72
mg,
0.28
mmol),
 1,3‐cyclopentadiene
 freshly
 distilled
 from
 dicyclopentadiene
 (7.3
 mg,
 0.11
 mmol),
 and
 benzaldehyde
 (28
 µL,
 0.28
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
 the
 resulting
mixture
was
stirred
at
room
temperature
for
24
hours.
A
saturated
solution
of
 ammonium
chloride
was
then
added
at
0
°C
and
the
product
was
extracted
with
diethyl
 ether.
 The
 organic
 phase
 was
 washed
 with
 H2O
 and
 brine,
 dried
 over
 Na2SO4,
 and


filtered.
 After
 removal
 of
 solvents
 with
 a
 rotary
 evaporator,
 an
 NMR
 analysis
 showed
 that
no
reaction
occurred.








Inside
a
nitrogen‐filled
glovebox,
Ni(cod)2
(3
mg,
10
mol%),
PPh3
(2.9
mg,
10
mol%)
and


DMF
(1
mL)
were
put
in
a
vial.
(Phenyldimethylsilyl)pinacolborane
(72
mg,
0.28
mmol),
 1,3‐cyclopentadiene
 (9
 mg,
 0.11
 mmol),
 and
 benzaldehyde
 (28
 µL,
 0.28
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
 the
 resulting
 mixture
 was
 stirred
 at
 room
 temperature
for
24
hours.
A
saturated
solution
of
ammonium
chloride
was
then
added
 at
0
°C
and
the
product
was
extracted
with
diethyl
ether.
The
organic
phase
was
washed
 with
 H2O
 and
 brine,
 dried
 over
 Na2SO4,
 and
 filtered.
 After
 removal
 of
 solvents
 with
 a


rotary
evaporator,
an
NMR
analysis
showed
that
no
reaction
occurred.
 


D
‐
Silaboration
without
aldehyde
 






Inside
a
nitrogen‐filled
glovebox,
Pd(acac)2
(9
mg,
10
mol%),
PEt3
(8.7
µL,
20
mol%)
and


toluene
 (0.75
 mL)
 were
 introduced
 to
 a
 vial.
 DIBAL‐H
 (1.5
 M
 in
 toluene,
 39.9
 µL,
 20
 mol%)
was
then
added
at
‐35
°C
and
the
mixture
was
stirred
at
room
temperature
for
15
 minutes.
Then
(chlorodimethylsilyl)pinacolborane
(66
mg,
0.3
mmol)
and
(Z)‐non‐2‐en‐ 4‐yne
 (36
 mg,
 0.3
 mmol)
 were
 sequentially
 added
 to
 the
 solution
 and
 the
 resulting
 mixture
was
stirred
at
room
temperature
for
24
hours.
Pyridine
(48.3
µL,
0.6
mmol)
and


iPrOH
 (45.9
 µL,
 0.6
 mmol)
 were
 then
 added
 to
 the
 crude
 and
 stirred
 for
 another
 12


hours.
After
removal
of
solvents
with
a
rotary
evaporator,
the
product
was
purified
by
 flash
 column
 chromatography
 (hexane/EtOAc
 40:1)
 to
 afford
 81
 mg
 (74%
 yield)
 of
 a
 colorless
liquid
identified
as
the
wanted
product.
1_{H
NMR
(500
MHz,
CDCl3):
δ
=
5.94
(d,}

J
=
11.5
Hz,
1H),
5.43
(dq,
J
=
6.5,
11.5
Hz),
4.01
(septet,
J
=
6.0
Hz,
1H),
2.19
(t,
J
=
7.5
Hz,
 2H),
1.49
(dd,
J
=
1.5,
6.5
Hz,
3H),
1.30
(s,
12H),
0.86
(t,
J
=
6.5
Hz,
3H),
0.07
(s,
6H).


PhMe₂SiB(pin) PhCHO

Ni(cod)₂ PPh₃

DMF r.t.

No reaction

PhMe₂SiB(pin) PhCHO

Ni(cod)₂ PPh₃ DMF r.t. No reaction Bu Si OiPr B O O

E
‐
Suzuki‐Miyaura
Coupling
 








The
diene‐product
from
the
silaboration
(17
mg,
0.046
mmol)
was
put
in
a
vial.
Inside
a
 nitrogen‐filled
 glovebox,
 (Z)‐(2‐bromovinyl)benzene
 (10
 mg,
 0.056
 mmol)
 was
 added
 with
Pd(PPh3)4
(5.4
mg,
0.0046
mmol)
and
potassium
carbonate
(32
mg,
0.232
mmol)
in


toluene
(0.5
mL).
Ethanol
(0.19
mL)
and
water
(0.19
mL)
were
then
added
outside
the
 glovebox
and
the
mixture
was
stirred
at
80
°C
for
4
days,
after
which
the
product
was
 extracted
with
DCM.
The
combined
organic
layers
were
dried
over
MgSO4
and
solvents


were
 evaporated
 under
 reduced
 pressure.
 The
 product
 was
 purified
 by
 flash
 column
 chromatography
(hexane/DCM
1:1)
to
afford
22
mg
of
a
mixture
of
the
wanted
coupling
 product
(47%
yield)
and
the
reduction
product
(protodeborylation).
1_{H
NMR
(400
MHz,} CDCl3):
δ
=
6.45
(s,
2H),
5.95
(d,
J
=
10.8
Hz,
1H),
5.57
(q,
J
=
6.4
Hz,
1H),
2.20
(t,
J
=
8
Hz,
 2H),
1.61
(d,
J
=
5.6
Hz,
3H),
1.4‐0.85
(m,
5H),
0.81
(t,
J
=
7.2,
3H),
0.13
(s,
6H).
 
 
 
 
 
 The
product
was
obtained
in
49%
yield
via
the
same
procedure
as
before.
 1_{H
NMR
(400
MHz,
CDCl3):
δ
=
6.40
(d,
J
=
15.6
Hz,
1H),
6.01
(d,
J
=
11.2
Hz,
1H),
5.79} (pent,
J
=
7.3
Hz,
1H),
5.53
(m,
1H),
2.22
(t,
J
=
7.6
Hz,
2H),
2.14
(q,
J
=
6.8
Hz,
2H),
1.53
(d,
 J
=
7.0
Hz,
3H),
1.45‐1.25
(m,
9H),
0.93‐0.86
(m,
6H),
0.29
(s,
6H).
 
 
 
 The
product
was
afforded
in
35%
yield
via
the
same
procedure
as
before.
 1_{H
NMR
(400
MHz,
CDCl3):
δ
=
7.42
(s,
1H),
7.32
(s,
1H),
6.33
(s,
1H),
5.99
(d,
J
=
10.8
Hz,} 1H),
5.58
(m,
1H),
2.25
(s,
2H),
1.60
(d,
J
=
6.4
Hz,
3H),
1.56‐0.90
(m,
5H),
0.05
(s,
6H).
 
 
 Bu Si Ph OH Bu Si OH Bu Bu Si OH O