P, S, C C C o Nptel PDF
P, S, C C C o Nptel PDF
Lecture 23
Mechanism
The phosphorus ylides are prepared by quaternizing a tervalent phosphorus compounds
with an alkyl halide and treating the salt with base. The phosphorane adds as a carbon
nucleophile to the carbonyl group and the resulting intermediate reacts via a cyclic
intermediate to form the alkene (Scheme 2-3).
X O
Ph R R' SN2 Ph R' Base Ph R' Ph R'
R R'' H
Ph P : + Ph P Ph P Ph P
H X
Ph Ph H Ph R Ph R
Triphenylphosphine Phosphonium salt Phosphorus ylide or phosphorane
Notes:
Other phosphines may be used for this reaction, but the choice should not contain a
proton that could be abstracted by base, because a mixture of desired and undesired
ylides would be formed.
Usually strong bases such as BuLi, NaH and NaNH2 are used.
Prefered anti attack of ylide, Bond rotation follows to the result often gives
minimizing steric hinderance form the betaine the z-alkene
L S PPh3 L S L O S S
S L O PPh3 L L
O
Scheme 3
Simple phosphoranes are very reactive and are unstable in the presence of air or moisture.
They are therefore prepared in a scrupulously dry solvent under nitrogen and the carbonyl
compound is added as soon as the phosphorane has been formed.
More stable phosphoranes are obtained when a –M substituent is adjacent to the anionic
carbon (Scheme 4). However, although they react with aldehydes, they do not do so
effectively with ketones and for this purpose modification has been introduced in which
triphenylphosphine is replaced by triethyl phosphate (Wadsworth-Emmons Reaction).
Br PhLi R2C=O R
NC Br + P(OEt)3 NC P(OEt)3 NC P(OEt)3 NC + (EtO)3P=O
R
Scheme 4
Examples:
O O
Me Me
Me Ph3P=CH2 Me
63% MeO
MeO O
O CHO O
Me Me
O + O
Me Me
63%
OAc OAc
PPh3
MeO2C MeO2C
PPh3
O Base
R
N R N
H H
Scheme 5
Mechanism
Scheme 6
Examples
PPh3
t-BuOK CO2Et
O
CO2Et 64% N Me
N H
H
Me
B. Danieli, G. Lesma, G. Palmisano, D. Passarella, s. Silvani, Tetrahedron 1994, 50, 6941.
PPh3
t-BuOK
O Me
96% N
N Me H
H
O
EtO3P + + R3CX EtO P CR3
OEt
Scheme 7
Mechanism
Et X
O O
EtO3P: + R C X EtO P CR3 P CR + EtX
3 EtO OEt 3
OEt
Scheme 8
It is an alternative method for the synthesis of alkyl phosphonate esters (Scheme 9-10).
The yield of the process is usually less compared to the above mentioned Michaelis-
Arbuzov reaction.
O O
NaH
EtO P H EtO P R
EtO R-X EtO
Scheme 9
Mechanism
O O O
NaH R X
EtO P H EtO P EtO P R
EtO -H2 EtO Na -NaX EtO
Scheme 10
Scheme 11
Examples
P(OEt)3 O
MeO2S Cl MeO2S POEt2
S 92% S
S. S. Chou, D.-J. Sun, J.-Y. Huang, P. K. Yang, K.-C. Lin, Tetrehedron Lett. 1996, 32, 7279.
O O
I O
POEt2
P(OEt)3
Me Me
94%
Me Me
R. W. Driessen, M. Blouin, J. Org. Chem. 1996, 61, 7202.
O
O light
P OMe
P OMe
O
O 40%
M. S. Landis, N. J. Turro, W. Bhanthumnavin, W. G. Bentrude, J. Organometallic Chem. 2002, 646, 239.
O O
EtO P Na + Br n
EtO P n
OEt OEt
I Pergament, M. Srebnik, Org. Lett. 2001, 3, 217.
O O
BnO P + CH2O + BnNH2 BnO P NHBn
H EtOH
OEt OEt
H.-J. Cristan, a. Herve, D. Virieux, Tetrahedron 2004, 60, 877.
PPh3, DEAD, H
HO + Ph3PO
HO
Nu
Scheme 13
Mechanism
O O PPh3 O PPh3 HO
N OEt Ph3P: N OEt H N OEt
EtO N EtO N EtO N
O H
O O
DEAD = Diethylazodicarboxylate Phophonium salt
O O
H
N OEt N OEt :Nu
Ph3P O + EtO N EtO N + Ph3P O Nu
H H
H O O SN2
-Ph3PO
Scheme 14
Examples
O O
i. DEAD, Ph3P, ArCOOH
ii. NaOH
OH t-Bu OH t-Bu
99%
M. T. Crimmins, J. M. Pace, P. G. Nantermet, A. S. Kim-Meade, J. B. Thomas, S. H. Watterson, A. S. Wagman, J.
Am. Chem. Soc. 1999, 121, 10249.
O O
i. DEAD, Ph3P, ArCOOH
ii. NaOH
OH t-Bu OH t-Bu
99%
M. T. Crimmins, J. M. Pace, P. G. Nantermet, A. S. Kim-Meade, J. B. Thomas, S. H. Watterson, A. S. Wagman, J.
Am. Chem. Soc. 1999, 121, 10249.
H CHO
POCl3
Ar-H or ARCHO or
R R' DMF R R'
Scheme 15
Mechanism
The formylating agent is generated in situ from DMF and POCl3 (Scheme 16).
Cl O O
O Cl
P P Cl Cl P
O O O Cl O
.. Cl Cl O Cl
Me P H -Cl H Cl ..
N H + Cl Cl Me N Me N H
Cl Me N
Me Me Me
Me
Me Me Me .. Me Me .. Me Cl
N N H N O
H
+ H
H -Cl -H Cl Me N O P Cl
Cl H Cl
H Me
Vilsmeier Reagent
H2O -Me2NH
CHO
Scheme 16
Problems
OH
i. DEAD, Ph3P, PhCOOH
1. Ph Me
ii. K2CO3
O3
2. Ph3P
OH
PPh3, Br2
3. Ph Me
2P(OEt)3
4.
NO2
PPh3
O base
5.
N CF2-CF3
O H
Ph3P OMe
6.
H3O+
O
MeMgBr
7.
H3O+
Text Books
Lecture 24
Mechanism
O Ar O O O
O O S Ar
O O n-BuLi O O O S
R S R S R' H R O R' O O
Ar Ar R R
O O
H H O
O
O S Ar
-OAc R' O Na(Hg) .
. R'
R R' O Na(Hg)
R
R' R
O R .
SO2Ar O OAc
Scheme 1
Sulfones having -hydrogen can be coupled with aldehydes using base (Scheme 2).
OTBS
OHC
OH
OTBS
Me n-BuLi
+
THF O O SO2Ph
Me
O O SO2Ph
Scheme 2
Examples
Me
N O
O2S O
H H Me Me H H Me
i. n-BuLi, DME
O + N O O
ii. Na(Hg), Na2HPO4
H H OMe O MeOH H H OMe
O Me 45.6%
D. J. Hart, J. Li, W.-L. Wu, A. P. Kozikowski, J. Org. Chem. 1997, 62, 5023.
OTBDMS
SO2Ph OTBDMS
i. NaN(TMS)2, THF
+ ii. Bz-Cl, THF
H O N O
iii. Na(Hg), Na2HPO4
O MeOH
O O
N O
The first stage of the reaction of a sulfur ylide with an aldehydes or ketone compound
consists of nucleophilic addition, the resultant adduct then proceeds intramolecular
nucleophilic substitution to give an epoxide (Scheme 3). In case of
-unsaturated
compounds, based on the nucloephilicity of the ylide either epoxide or cyclopropanation
could be formed.
CH3 CH3
CH2=S O CH2=S=O O
O CH3 O CH3
+ R R
R R -DMS R R
-DMSO
R R
Mechanism
CH3
CH3
O CH2=S
O S O
CH3 -DMS
R R CH3 R R
R R
CH3 O
O
O CH2=S=O
R R
CH3 H3C -DMSO
R O
S
R
R CH3
Scheme 3
Recently, chiral version of the reaction has been extensively studied for the synthesis of
optically active epoxides as the principle shown in Scheme 4. The products are usually
obtained with high enantioselectivity.
Ar
R*R*S RCHO O
BnBr S
Base *R R* R Bn
Optically Active
chiral
Scheme 4
Examples
Me Me
Me NaH, DMSO Me
Me Me
O OH Me3SI O OH
MeO MeO
NaH, DMSO
O O
Me3SI
MeO MeO
Sulfur ylides rearrange as shown in Scheme 4. In case of allylic sulfur ylide, [3,2]-
sigmatropic rearrangement is observed.
R'
[1,2]
R' R S
R S S S R
R" R"
R"
EtBr I NaH
S S S
[1,2]
[3,2]
SEt
SEt
Scheme 4
Aza- and oxa-sulfonium salts give ylides that can rearrange to give useful aromatic
compounds (Scheme 5).
R'
R S R R
N N NH
H
SR SR
R'
S
O O OH
H
SR SR
Scheme 5
Dimsyl anion is very reactive nucleophile and can be used for various synthetic
applications. The sulfur substituent can be easily removed by reduction or thermally
(Scheme 6).
O
S -Br
Br + S
O
heat
-MeSOH
O
Ph OEt + -OEt Ph Zn-AcOH Ph
S S
O O O
O
Ph Zn-AcOH Ph
Ph NaH S
S
2MeI O O O
O O
CO2Et CO2Et
Ph NaH Ph Zn-AcOH Ph
S S
O O BrCH2CO2Et O O O
Scheme 6
The compound containing an activated C-H bond can underogo reaction with diphenyl or
dimethyl disulfide in the presence of base to give substituted sulfide that could be readily
oxidized to sulfoxide (Scheme 7). The latter readily undergoes elimination on heating to
give -unsaturated carbonyl compound.
O O O O O O
S Ph S S
OH Ph S Ph Oxidation Ph heat
Scheme 7
This method gives an effective route for the transformation of 1,2-diol to alkenes. The
cyclic thiocarbonate formed from 1,2-diol and thiocarbonyldiimidaole undergoes reaction
with phosphorus reagent via a syn elimination to afford alkene (Scheme 8).
OH N
R2S
+ CO2 + 2HCl + S P(OR')3 R = Cl,
N
P(OR')3
OH
Mechanism
N N HS
- P(OR')3 O
OH N N O :P(OR')3 O
S S :
O O P(OR')3 O
OH NH
-2 N
:P(OR')3
O O
P(OR')3 P(OR')3
CO2 + P(OR')3 O
O
-
Scheme 8
Examples
Me N N Me
N N
HO
HO Me
N
P-Me
N
Me
M. F. Semmelhack, J. Gallagher, Tetrahdron Lett. 1993, 34, 4121.
O N N O
TBDMS Thymine N N TBDMS Thymine
O O
P(OEt)3
OHOH
Synthesis of chiral sulfoxide can be accomplished from sulfinyl chloride by reaction with
chiral auxiliaries followed by substitution of the separated diastereomers with
nucleophiles (K. K. Andersen, Tetrahedron Lett. 1962. 3, 93).
O O
Separation of Diasteroisomers
S S
R Cl + HO R Nu
Nu *
Optically Active
Menthol
Optically Active
Mechanism
..
O -HCl .. .. Separation O
O O
+ S S
S + HO S R O
R Cl .... R O R O
Diastereoisomers
:NuH
Separation
..
.. .. O
O :NuH O +
+ S
S S R Nu HO
R Nu R O
HO Optically Active
Optically Active
-
Scheme 9
Example
..
O O
Cholesterol S Ph
S
Cl
Ph MgX HO
78% yield; 91% ee Cholesterol
S H Base S R
S H R-X S H
Mechanism
S H Base S R-X S R
S H S H S H
S
H
S
Scheme 10
Examples
NaNH2, EtOCH2O(CH2)2ONa S
S
+ O S
S DME HO
O S Ti(Cp)2(P(OEt)3)2
+ + Ph
Ph
S Ph THF
44.4% 29.6%
Y. Horikawa, M. Watanabe, T. Fujiwara, T. Takeda, J. Am. Chem. Soc. 1997, 119, 1127.
S N
N S (DPDS)
CO2H
2,2'-dipyridyl disulfide O
HN
+
PPh3, solvent, heat
O S
OH
Mechanism
O
PPh3
O O
H
:PPh3 O
S N N S
N S + HO
N S PPh3 +
N S
HO
PPh3
H O O OO
O N S S S
HN
+
N: N
O S O
H O
HO
CO2H
AcO
AcO DPDS, PPh3 O
O
67%
HO
HO C5H11
OH
E. J. Corey, K. C. Nicoloau, L. S. Melvin, Jr., J. Am. Chem. Soc. 1975, 97, 653.
Scheme 11
OR i. Tf2O, CH2Cl2 OR
RO O RO
O ii. ROH O
RO S Ph RO OR'
OR iii. Base OR
Mechanism
O
OR O O OR OR
RO RO .. O CF3 RO ..
O HO-R
O
F3C O CF3 O: -S(Ph)OTf O: ..
S Ph RO S Ph RO
RO
OR -OTf OR OR
OR OR
RO H RO
O Base O
RO O RO O
R R
OR OR
Scheme 12
Examples
i. Tf2O, toluene
ii.
BnO Me Me Me
BnO
OO OH BnO O
BnO O
S Ph Me BnO
BnO
OBn BnO
Me
iii.
70% = 2:1)
t-Bu N t-Bu
D. Kahne, S. Walker, Y. Cheng, D. Van Engen, J. Am. Chem. Soc. 1989, 111, 6881.
i. Tf2O, toluene
HN
O
MeO
ii. MeO O N3 O
AcO N3 OMe AcO
AcO O Ph AcO
OH O NH
AcO S AcO
TfHN O O
Me TfHN
95% OMe
iii.
t-Bu N t-Bu
D. J. Silva, H. Wang, N. M. Allanson, R. K. Jain, M. J. Sofia, J.Org. Chem. 1999, 64, 5926.
Problems
A. Complete the following reactions.
SO2Ph
Na(Hg)
1.
OAc
S H3O+-Hg2+
2.
S
O O
heat
Ph
3.
O Me
S CH2
Me
4.
Me
S OTf
CHO
Me
5.
Br NaH
Me
O
O S CH2
6. Me
B. How would you use sulfur containing reagents for the following conversions?
Ph Ph
1. O
Me Me O
2 CHO
O O
Br
3. Cl
Text Books
M. B. Smith, Organic Synthesis, 2nd Ed., McGraw Hill, Singapore, 2004.
R. O. C. Norman and J. M. Coxon, Principles of Organic Synthesis, CRC Press, London,
2009.
Lecture 25
Both silicon and carbon have similarity in having valency of four and formation of
tetrahedral compounds. Regarding the differences, carbon forms many stable trigonal and
linear compounds having bonds, while silicon forms few. This is because of the
strength of the silicon-oxygen σ bond (368 KJ mol-1) as well as the relative weakness of
the silicon-silicon (230 KJ mol-1) bond.
X- Me Me Me
X Me Me Me SN1 X-
C C C C
Me Cl Me Me Me X
Me SN2 Me
Unfovourable stable t-butyl carbocation
X -
Me Me SN1 Me
X Me X Me
Si Me Si Si
Si SN2 Me Me
Me Me Me Cl Me Cl
Very fovourable Does not occur
Scheme 1
Let us compare the SN2 reaction at silicon with the SN2 reaction at carbon. Alkyl halides
are soft electrophiles but silyl halides are hard electrophiles. The best nucleophiles for
saturated carbon are neutral or based on elements down the periodic table, whereas the
best nucleophiles to silicon are charged or based on highly electronegative atoms. A
familiar example is the reaction of enolates at carbon with alkyl halides but at oxygen
with silyl chlorides (Scheme 2).
X SiMe3
Me3Si O O O
O
SN2 R X
SN2
Scheme 2
Furthermore, the SN2 reaction at carbon is not much affected by partial positive charge
(+) on the carbon atom. However, the SN2 reaction at silicon is affected by the charge
on silicon. For example, the most electrophilic silyl triflates react 109 times fast with
oxygen nucleophiles than silyl chlorides do (Scheme 3).
MeOH
..
H H H :OMe
Me3Si OTf H OMe Me3Si OTf SiMe3
-H
SiMe3 SiMe3 Ph O
Ph O: Ph O Ph O
..
-OTf - OTf SiMe3
-Me3Si-O-SiMe3
Silicon based protecting groups are the versatile for alcohols. They can be easily
introduced and removed in high yield without affecting the rest of the molecule in a wide
range of conditions. The rate of the introduction as well as the removel depends on the
steric nature of the alcohols as well as the silyl group (Scheme 4).
base F F
ROH + R3SiCl ROSiR3 ROSiR3 RO + R3SiF
Scheme 4
Cl Cl Cl Me Cl
Me Si Me Si Me Ph Si Me Me Si Me
Me
Me Me Ph Me Me
Me Me Me
Me Me
The silyl group can be used to protect the terminus of the alkyne during the reaction and
can also be easily removed with fluoride or sodium hydroxide (Scheme 5).
E
SiMe3
R
Scheme 5
10.3.3.1 Alkynylsilanes
Similar to alkynes, silylated alkynes are too nucleophilic towards electrophiles. However,
the presence of silicon has a dramatic effect on the regioselectivity of the reaction: the
attack occurs only at the atom directly bonded to silicon (Scheme 6). This is due to the
stabilization of the intermediate vacant orbital by the filled C-Si sigma orbital.
vacant p orbital
R SiMe3 SiMe3
R SiMe3 SiMe3 or R R filled C-Si orbital
E E E
E E
no stabilization Stabilized by silicon
Scheme 6
The stabilization of the cation weakens the C-Si bond by the delocalization of the
electron density. The attack of a nucleophile on silicon readily removes it from the
organic fragment and the net result is the electrophilic substitution in that the silicon is
replaced by the electrophile (Scheme 7).
O Cl-
H3C Cl SiMe3
SiM3 SiM3
AlCl3 O
H3C
O+
O Stabilized by -silicon
Me
alkynyl ketone
Scheme 7
The controlled reduction of alkynyl silanes can produce vinayl silanes. The
stereochemistry depends on the methods used. Lindlar hydrogenation takes place via cis
fashion, while red Al reduction of propargylic alcohol gives E-isomer (Scheme 8).
H H
Red Al OH Na
Me3Si
OH Me3Si Red-Al: MeO O
Al H
H3O E 2
H
OMe
H O H
Me3Si Al Me3Si
Red-Al H O
Me3Si
OH OMe Al O
H
ligand MeO O O O
hydroalumination MeO
exchange Al O
O
OMe
MeO
H3O H
Me3Si OH
Hydrolysis
H
Scheme 8
Alternatively, hydrosilylation of simple alkyne can give E-vinyl silane that could be
irradiated to afford Z-isomer (Scheme 9).
H Me3Si
Me3SiH light H
Ph H SiMe3 Ph
Ph
H2PtCl2 H
H
Scheme 9
2 t-BuLi Me3SiCl
Br Li SiMe3
Scheme 10
The reactions of vinyl silanes with electrophiles afford an effective route for the synthesis
of alkenes with high stereoselectivity. The stereochemistry is important because the
exchange usually occurs with retention of geometry (Scheme 11).
E-Vinyl Silane Cl
H Me3Si H
DCl rotation
Ph Ph SiMe3 Ph D Ph
SiMe3 D
D
D
stabilized by silicon
Z-Vinyl Silane Cl
SiMe3 SiMe3 Me3Si D D
DCl rotation
Ph Ph H Ph H Ph
D
D
stabilized by silicon
Scheme 11
The same sort of mechanism involves for reactions of aryl silanes with electrophiles. In
these reactions the silyl group is replaced by the electrophiles at the same atom on the
ring. This is called as ipso substitution (Scheme 12).
Nu
SiMe3 SiMe3 E SiMe3 E
E E
E
H tabilized by -silicon ipso substitution
no stabilization
Scheme 12
Me O
Br Li SiMe3
Me Me Me Me
Li Me3SiCl MeCOCl-AlCl3
+ Me3SiCl
Allylsilanes can be readily prepared from allyl halide via Grignard reaction (Scheme 13).
R R R
Mg Me3SiCl
R' Br R' MgBr R' SiMe3
THF
Scheme 13
Allyl silanes are more reactive compared to vinyl silanes (Scheme 14). This is because
vinyl silanes have C-Si bonds orthogonal to the p orbitals of the alkene, in contrast, allyl
silanes have C-Si bonds that can be parallel to the p orbitals of the double bond so that
interaction can be possible. However, both react with electrophiles at the ipso atom
occupied by silicon. In both cases a-silylcation is an intermediate.
SiMe3 siMe3
R
R
No intreaction between Interaction between
orthogonal orbitals parallel orbitrals
For example,
Cl Cl
SiMe3 SiMe3
O SiMe3 CH3COCl
O O
TiCl4 TiCl4
O O
-allyl cation -allyl cation
Scheme 14
In optically active compounds, one enantiomer of the allyl silane gives one enantiomer of
the product (Scheme 15). The stereogenic centre next to silicon disappears and new one
appears.
Scheme 15
Allyl silanes also attack carbonyl compounds in the presence of Lewis acid which
activates the carbonyl group (Scheme 16).
Cl
OTiCl3 OH
PhCHO-TiCl4 H+
SiMe3 SiMe3 Ph
Ph
Scheme 16
Silyl epoxides can be prepared from vinyl silanes with peroxy acids or from ketones
(Scheme 17).
Li
Li
n-BuLi RRCO H O -LiCl O
Me3Si Cl Me3Si Cl Me3Si R H R
-n-BuH Cl R Me3Si R
Scheme 17
Peterson olefination, which is closely related to the Wittig reaction, can be carried out in
two ways using either acid or base and the geometry of the alkenes can be controlled
accordingly (Scheme 18).
O
M
M = Li, Mg
SiR3 Basic or Acidic
Work up
Scheme 18
Mechanism
The reactions are anti under acidic conditions and syn under basic conditions (Scheme
19). The stereoselectivity is due to involvement of a cyclic transition state under basic
conditions, whereas under acidic conditions an acylic mechanism involves.
M
M O H O
O OH
H
SiR3
SiR3 SiR3
Basic Work up
M
O H base O O
SiR3
SiR3 SiR3
cis elimination
Acidic Work up
OH OH2 OH2
H -H2O
SiR3 SiR3 R3Si
trans elimination
Scheme 19
Examples
O
TMS Li, CeCl3
KH
t-Bu t-Bu
B. Henkel, B. Beck, Westner, B. Mejat, A. Domling, Tetrahedron Lett. 2003, 44, 89.
OH
TFAc KH, F
F TMS
A. G. M. Barrett, J. A. Flygare, J. Org. Chem. 1991, 56, 638.
Problems
O OMe
Me3Si SiMe3
OH MeO
K2CO3/MeOH
1. SiMe3
O i.TMSOTf
2.
ii. PhCHO, TiCl4
OH
KH, KF
3.
SiMe3
TMS
AcCl, AlCl3
4.
TMS
I2
5.
6. SnCl4
OHC SiMe3
SiMe3
NH3
7. HO CF -CF3
Ph 2
Text Books
Lecture 26
Boron containing compounds find wide applications in organic synthesis. Borane (BH3)
is commercially available in the form of complexes generally with THF, Et2O and Me2S.
It can also be prepared in situ by the reaction of NaBH4 with BF3∙OEt2 complex (Scheme
1):
Scheme 1
Organoboranes are synthesized by the addition reaction of borane to alkenes and alkynes.
The reaction of borane with alkenes gives alkylboranes that readily proceed oxidation in
the presence of alkaline hydrogen peroxide to yield alcohols (Scheme 2). The conversion
of C-B bond into a C-OH takes place with retention of stereochemistry.
Scheme 2
In case of sterically hindered alkenes such as trisubstituted ones, it is more difficult to add
three alkenes to borane. This becomes the basis for the development of a variety of
borane derivatives. For some examples, see:
B BH2
H B 2
H
BH
Disiamylborane Thexylborane 9-Borobicyclo[3.3.1]nonane (-)-Diisopinocampheylborane
Sia2BH 9-BBN (-)-IPc2BH
Mechanism
The hydroboration reactions proceed by cis addition of hydrogen and boron to alkenes,
probably via a four-centred cyclic transition state (Scheme 3).
R'
H B R' H R'
HBR'2 O-OH
H H B
R R R R'
H
Borane attacks from Boron adds as an electrophile and Boron hydrolysis begins
the less hindered face hydride as the nucleophile in a with the attack of peroxide
cis-fashion. Regiochemical control
H R' H H
-OH O-OH
B R' O R' O OR' OH
R O OH R B R B
R' OR'
The bond to boron then OH
migrate to oxygen
two more addition/mirgration takes place
H OR' H OR'
OH
O OH +
R H O OR' R O OR' Na3BO3
Scheme 3
Examples:
HO O O
H O H H
BHCy2, THF HO
H
Me Me + Me
h H NaBO3 4H2O H H h H
h
H2O
O Ph H
O Ph H
9-BBN, THF O Ph H OH
+
Ph Ph Ph
H2O2, NaOH
NO H EtOH NO2H OH
NO2H
2
55% 15%
Hydroboration and oxidative strategy provides an effective route for the transformation
of alkenes to alcohols with retention of configuration at the boron-bearing carbon
(Scheme 4).
Me Me Me
BH3 H2O2/ OH
heat OH
3B
Sia2BH OH
H2O2/NaOH
Scheme 4
Asymmetric version of this process has made a remarkable progress using chiral boranes
with excellent enantioselectivity (Scheme 5).
(-)-Ipc2BH OH (-)-Ipc2BH OH
CH3CHO
CH3CHO
O NaOH,H2O2 O O NaOH,H2O2 O
Yield: 92%
Yield: 68% BH
ee: 100%
ee: 100%
2
(-)-Ipc2BH OH (-)-Ipc2BH OH
CH3CHO (-)-Ipc2BH
CH3CHO
O NaOH,H2O2 O S NaOH,H2O2 S
Yield: 81% Yield: 80%
ee: 83% ee: 100%
Scheme 5
Alkylboranes also undergo isomerization on heating to give products that contain the
boron atom at the least hindered position of the alkyl chain (Scheme 6).
Scheme 6
BH3 AgNO3/KOH
B
3
Me Me
4,7-Dimethyldecane
Scheme 7
H H H OH H
B2H6 CO, 70 atm, 150 oC
B
NaOH, H2O2
H H
Scheme 8
Mechanism
The reaction involves migration of alkyl groups from boron to the carbon atom of CO
(Scheme 9).
O 2nd migration O
CO 1st migration R
R3B R3B C=O R2B C=O R B R B
R R
R R
3rd migration
NaOH
R3COH R3CBO
H2O2
Scheme 9
In presence of a small amount of water, migration of third alkyl group from boron to
carbon can be inhibited to give dialkylketone (Scheme 10).
BH2 OAc
B B
OAc
H
O
OAc
Scheme 10
The carbonylation sequence can be modified to give aldehydes and primary alcohols
(Scheme 11).
KOH
OH
9-BBN LiAlH(OMe)3
OAl(OMe)3
CO
H NaH2PO4/K2HPO4
B
B O
pH 7/H2O2
Scheme 11
O B OH
CHO B
3
THF, H2O
Scheme 12
Scheme 13
O
BH
O H2O
B O B OH
O HO
Br2/CH2Cl2
I2/NaOH
-78 oC
H
Br Br I
H B O
O
NaOMe/MeOH
Br O
Br B O
H OMe
H
-Br
Br
Scheme 14
10.4.3 Vinylboranes
Borane with alkynes gives vinylboranes that serve as useful intermediates in organic
synthesis. For example, 1-hexyne with catcholborane yields trans-1-alkenylborone that
can be converted into trans-vinyl iodide and cis-vinyl bromide that are substrate
precursors for the C-C coupling reactions using palladium catalysis (Scheme 14).
Vinylboranes can also be converted into aldehydes, ketones or alkenes and the reactivity
and selectivity depend on the nature of organoboranes used (Scheme 15).
BR2 OH O
R2BH H2O2, NaOH
Et Et Et
Et Et Et
B(C5H11)2
(C5H11)2BH H2O2, NaOH OH O
Et H Et H
Et H H
R2BH Me Me AcOH, O oC
Me Me
Me Me
BR2
Scheme 15
Me Me
Pd2(dba)3, P(t-Bu)3
MeO Cl + (HO)2B MeO
KF, THF
Me Me
Pd(OAc)2, PCy3
t-Bu Cl + (HO)2B t-Bu
KF, THF
Scheme 16
Examples:
I Pd(Pt-Bu3)2 Me
Me
B(OH)2
+ MeO2C
MeO2C CsF
OMe
M. Rubina, M. Rubin, V. Geforgyan, J. Am. Chem. Soc. 2003, 125, 7198.
I
Pd(OAc)2, P(o-tol)3
I + (HO)2B OMe OMe
N K2CO3 N
SO2Ph SO2Ph
Problems
O
2. BH3, THF
O
N NaOAc, H2O2
B2H6
3.
NaOH, H2O2
9-BBN
4. Me
NaOH, H2O2
ClNH2
5. B
3
B. How would you utilize boron-containing reagents for the following conversions?
OH
1.
H O
2.
3.
Text Books
Lecture 27
+ Li SnMe3
OTs SnMe3
Scheme 1
The hydrostannylation of an alkyne with tin hydride affords kinetically controlled Z-vinyl
stannane. If there is an excess of tin hydride or sufficient radicals are present,
isomerization may take place to afford the more stable E-isomer (Scheme 2-3).
Bu3Sn-H
Bu3Sn
AIBN OSiMe2t-Bu
OSiMe2t-Bu
Scheme 2
Mechanism
Bu3Sn R
R Bu3Sn H SnBu3
AIBN R Bu3Sn . +
Bu3Sn-H Bu3Sn . H H
H . Z
-N2
Bu3Sn R Bu3Sn R H R N 2 .
H . N
Bu3Sn . + CN CN
H H Bu3Sn H Bu3Sn H CN
Z AIBN
Radical Initiator
Scheme 3
SnBu3 Pd2(dba)3
AsPh3, CuI
+ I
Me O DMF Me
O O O
46%
O O
Pd2(dba)3, AsPh3, NMP
I 96%
Bu3Sn
Scheme 4
Mechanism
R R'
reductive Pd(0)L2 R-X
elimination
oxidative addition
L
R'
Pd L
X
L R Pd
R L
cis-trans L R'-Sn(R")3
R'
isomerization Pd transmetallation
R L
X-Sn(R")3
Scheme 5
If the electrophile is a vinyl triflate, the addition of LiCl to the reaction is essential
because the chloride may displace triflate form the palladium σ-complex. The
transmetallation takes place with chloride on palladium and not with triflate (Scheme 6).
O OTf
Me Me Me
LDA Pd(Ph3)4, LiCl
Tf2NPh SnBu3
Me3Si
19:1 (E,E)/(E,Z)
O OTf
Me i Me Pd(Ph ) , LiCl Me
Pr2NMgBr 3 4
Tf2NPh SnBu3
Me3Si
49:1 (E,E)/(E,Z)
Scheme 6
Examples:
O O
I SnBu3
O O
O Pd2(dba)3, AsPh3 O
Cl
cyclohexane
Bu3Sn
38%
Allyl stannanes are important reagents because they can be used for allylation to
aldehydes with excellent stereocontrol (Scheme 7).
OH
SnBu3 PhCHO H
Bu3Sn
Ph
heat O
R
OH
SnBu3 PhCHO H
Bu3Sn
Ph
heat O
R
Scheme 7
The asymmetric allyllation of aldehydes with ally stannanes has also been explored
(Scheme 8).
OBn OBn Me OBn Me
MgBr2
CHO +
SnBu3
OH OH
10:1
OH
Ti(OiPr)4, BINOL
SnBu3
F3C CHO +
F3C
97% ee
Scheme 8
Mechanism
~70 oC .
N CN 2 + N2
NC N
CN
AIBN
Radical Initiator
. .
Initiation + Bu3Sn
+ H SnBu3
CN CN
MeO MeO
.
Propagation Bu3Sn + + Bu3SnBr
.
Br
MeO MeO
.
Bu3Sn H + . + Bu3Sn
Scheme 10
The alkyl radical can also undergo addition to alkenes to give alkane via the formation
new carbon-carbon bond. Both inter- and intramolecular versions of this process have
been explored. For example, Bu3SnH mediated addition of nucleophilic radical to
electrophilic alkene can be accomplished in good yield (Scheme 11).
electrophilic alkene
Bu3SnH CN .
I .
CN
AIBN 5 mol%
nucleophilic radical
-Bu2Sn. SnBu3 H
CN
Scheme 11
O O O O O O
Bu3SnH Bu3SnH
EtO OEt EtO OEt EtO OEt
.
AIBN 5 mol% C4H9 O
Cl O C4H9
electrophilic radical nucleophilic
alkene
Scheme 12
Examples:
. Me Me
Me Me
CH2I CH3
TBTH Me
Me Me
Me Me 80%
H3C
IH2C .
O O OH O
TBTH
CO2Et CO2Et
.
AIBN
CO2Et CO2Et
Ph-H
45%
Problems
A. How would you utilize tin-containing reagents in the synthesis of the following
compounds?
Me Me
Ph O O
CO2Me O
Me Me Me
O Bu3SnH
1. SMe
AIBN
n-BuLi
2.
S Bu3SnH
CHO
heat
3. SnBu3 +
H
Bu3SnH, Pd(0)
+ Br Ph
4.
OH
OTf Pd(0), CO
5. + SnBu3
CO2Me
Bu3SnH
6. Br + CO2Me
AIBN
Text Books
P. Wyatt, S. Warren, Organic Synthesis, John Wiley & Sons Ltd, West Sussex, 2007.