Highly diastereoselective hydrosilylations of allylic alcohols

Article abstract of DOI:10.1039/c4cc00138a

The highly syn-selective hydrosilylation of allylic alcohols was developed which, following oxidation, provided 1,3 alcohols containing two contiguous stereocentres. Through judicious choice of silane the complementary anti-selective hydrosilylation was a

Full text of DOI:10.1039/c4cc00138a

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Highly diastereoselective hydrosilylations of
allylic alcohols†
Cite this: Chem. Commun., 2014,
50, 3501
Mark G. McLaughlin and Matthew J. Cook*
Received 7th January 2014,
Accepted 11th February 2014
DOI: 10.1039/c4cc00138a
www.rsc.org/chemcomm
The highly syn-selective hydrosilylation of allylic alcohols was developed examples, however the scope of these reactions tends to be poor.8 The
which, following oxidation, provided 1,3 alcohols containing two con- more developed field is to use a pre-existing stereogenic centre to
tiguous stereocentres. Through judicious choice of silane the comple- direct the addition to one of the faces of the alkene thus forming
mentary anti-selective hydrosilylation was also developed. This protocol diastereoisomers in the process.9
was applied to the synthesis of an all syn polyketide stereotriad.
Tamao and Ito reported an intramolecular hydrosilylation of silyl
ethers onto 1,1-disubstituted alkenes using H2PtCl6 as the catalyst.10
Organosilicon compounds are important tools in organic synthesis, Following oxidation, 1,3-diols were produced with two contiguous
with their use as protecting groups being demonstrated in numerous stereogenic centres being formed in moderate to good selectivity in
total syntheses. Their use as a synthetic handle for building most cases with the syn-diastereomer predominating.11 Since this
molecular complexity is much less developed with a few notable work, other groups have reported a range of hydrofunctionalisations
exceptions. Organosilanes can be used as the transmetallating followed by in situ oxidations to afford these important scaffolds.12
partner in Hiyama and Denmark–Hiyama cross coupling reactions,1 Previously we demonstrated, the combination of PtCl2 and XPhos as
as a masked hydroxyl group via the Fleming–Tamao oxidation,2 and a catalyst system provides excellent regio and stereocontrol in the
as a precursor to many facile halogenation reactions.3 More recently, hydrosilylation of alkynes.13 We hypothesised that the use of bulky
these versatile compounds have also found use in medicinal phosphine ligands would also improve the stereochemical outcome
chemistry, with several drug candidates containing organosilicon of this reaction. In particular, the judicious use of ligand could
functionality.4
achieve high levels of diastereocontrol.14 Herein we report the use of
Due to the increased uses of these important compounds, the bulky phosphine ligands to enhance the syn stereochemical outcome
need for new, highly efficient and robust protocols to afford stereo- and a complementary intermolecular anti hydrosilylation of allylic
chemically defined organosilanes has increased, with transition alcohols.
metal catalysis proving invaluable. Alkene hydrosilylation has
Optimisation. Our optimisation studies began by examining allylic
become a cornerstone in this endeavour.5 Traditionally, this C–Si alcohol 1a (Table 1). This substrate was reported by Tamao and Ito to
bond formation has been catalysed by highly active catalysts such as perform the hydrosilylation in 83 : 17 diastereoselectivity.10 In this
Speier’s [H2PtCl6]6 or Karstedt’s (Pt2dvs3) catalyst.7 In spite of their report, they required the pre-formation of the silyl ether prior to the
high reactivity, these platinum catalysed hydrosilylation reactions hydrosilylation step. We reasoned that the both these steps could be
have drawbacks. They suffer from unwanted side reactions, as well performed concomitantly to provide a one-step procedure. Indeed,
as having issues with regio- and stereocontrol.
the use of Speier’s catalyst and Et2NSiMe2H provided the requisite
The anti-Markovnikov addition of hydrosilanes to 1,1-disubstituted diol following oxidation in the same diastereoselectivity as reported
olefins can result in the formation of a new stereogenic centre. by Tamao and Ito, albeit in reduced yield. To improve the reactivity
Stereoselectivity can be imparted into this reaction via two strategies: and stereoselectivity, we next examined the effect of bulky phosphine
reagent control and substrate control. The former requires chiral ligands and found XPhos L1 provided the optimal result in a 96 : 4
catalysts to be able to differentiate between the two prochiral faces of diastereomeric ratio and a much improved yield. Further
the alkene. This approach is still in its infancy with several notable optimisation came from a slightly modified oxidation procedure
which allowed us to obtain the diol in excellent yields and
diastereoselectivities. The use of ClSiMe2H provided similar
levels of diastereoselectivity with a much reduced yield and
School of Chemistry and Chemical Engineering, Queen’s University Belfast, Belfast,
BT9 5AG, Northern Ireland. E-mail: m.cook@qub.ac.uk
MeOSiMe2H failed to react. With these conditions in hand, we
began to examine the substrate scope for this reaction (Table 2).
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc00138a
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Table 1 Optimisation studies
Table 2 Substrate scope
Entry Pt source Ligand XMe2SiH
Oxidationa Yieldb (%) d.r.c
1
2
3
4
5
6
7
8
9
H2PtCl6
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
—
Et2NMe2SiH
Et2NMe2SiH
Et2NMe2SiH
Et2NMe2SiH
Et2NMe2SiH
Et2NMe2SiH
Et2NMe2SiH
Et2NMe2SiH
MeOMe2SiH
CIMe2SiH
A
A
A
A
A
A
A
B
A
A
37
12
71
47
40
35
n.r.
83
n.r.
43
84 : 16
80 : 20
96 : 4
90 : 10
85 : 15
80 : 20
—
96 : 4
—
96 : 4
PCy3
L1
L2
L3
L4
L5
L1
L1
L1
10
a
Conditions A: H2O2, KF, NaHCO3, THF, MeOH, H2O; B: H2O2, KF,
b
KHCO3, THF, MeOH, H2O. Combined yield of diastereoisomers.
c
Determined by 1H NMR analysis of the crude.
Syn-selective intramolecular hydrosilylation. The reaction is
tolerant of a wide range of functional groups with substituted
aromatic substrates 2b–d reacting in a similar fashion to the
parent phenyl substrate. Heteroaromatic substrates are also well
tolerated with furan and pyrrazole substrates 2e–f formed, albeit
in slightly reduced diastereoselectivities. The role of sterics is very
clearly exemplified by the alkyl substituents 2g–i where the more
hindered the substrate the higher the diastereoselectivity, with the
tert-butyl substrate 1i providing a single diastereoisomer. When
tertiary allylic alcohols are used, moderate diastereoselectivity is
observed as there is much less of a steric bias between the two
substituents at the alcohol centre. Finally, we examined the effect
of substituents at the central position (R3) of the allylic group and
found that other alkyl groups are well tolerated and can boost the
diastereoselectivity of the reaction when sterically encumbered
groups are present 2k–l. We were also able to hydrosilylate enol
ethers to form 1,2,3-triol type products 2m–p. These reactions
were highly diastereoselective and in all cases provided higher
stereoselectivities than the parent methyl analogues. To our
knowledge, this is the first example of a platinum catalysed
hydrosilylation of an enol ether substrate (Table 2).
To highlight this method we prepared a small polyketide
fragment. There are numerous methods to form polypropionate
fragments, however, the formation of the stereotriad with syn–syn
configuration 6 can be challenging.15,16 This motif is found in
many natural products including: swinholide A, erythromycin A
and discodermolide.17
a
b
Combined yield of diastereoisomers. Diastereoselectivity deter-
mined by 1H NMR analysis of the crude reaction.
Utilizing O-Piv-protected allylic alcohol (2S,3S)-5, which was
readily prepared,18 we performed our intramolecular hydro- reported all other diastereoisomers of 6 via an oxymercuration of
silylation reaction which, following oxidation, provided the cyclopropylcarbinols and this confirmed the stereochemistry of
corresponding syn,syn diol 6 in high diastereoselectivity. Cossy the product to be the syn,syn form (Scheme 1).19
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Scheme 1 Synthesis of all syn polyketide type fragment.
Fig. 1 Model for stereoselectivity.
substituent (A versus B). When either R1 or R2 is increased in size
the stereoselectivity also increases and the reaction is particularly
efficient when –OEt groups are present at R2 position.
In the intermolecular reaction there are no constraints on
the molecule and the stereoselectivity is governed by a combi-
nation of both steric and electronic factors. The minimization
of A1,2 strain plays a role as in the intramolecular case however,
positioning the OH group antiperiplanar to the incoming
hydridic nucleophile minimizes the buildup of negative charge
analogous to the polar Felkin–Anh model (C versus D).20 When
R1 = Ph, the steric and electronic factors almost cancel each
other out whereas when the steric bulk is increased the steric
factors override any electronic bias there may be thus providing
the anti product in excellent diastereoselectivity.
In conclusion, we have developed a highly diastereoselective
hydrosilylation protocol that provides the syn diastereomer in
high levels of diastereoselectivity. The reaction is very tolerant
of many functional groups providing 1,3-diols with two contig-
uous stereogenic centers following oxidation. This method has
been applied to the synthesis of a small polyketide fragment.
We have also developed an anti selective variant which is
particularly efficient for trialkylsilanes and sterically encum-
bered allylic alcohols.
Scheme 2 Anti-selective intermolecular hydrosilylation–oxidation.
Anti-selective intermolecular hydrosilylation. As the syn-products are
formed via an intramolecular hydrosilylation, we next examined the
intermolecular variant. We envisaged that the intermolecular path-
way would provide the complementary anti-stereoisomer, and this
was found to be the case. When Et3SiH was utilized an 87 : 13
diastereomeric ratio of 3a was obtained with the anti diastereomer
predominating. t-BuMe2SiH gave similar results with good anti
diastereoselectivity of 3b being obtained, however, both 3a and 3b
were inert to oxidation conditions.2 The more easily oxidized silanes,
Ph3SiH and BnMe2SiH were used and provided products 3c–d albeit
in a much less diastereoselective fashion.
The use of BnMe2SiH allowed for a one-pot hydrosilylation–
oxidation procedure, similar to the intramolecular variant
(Scheme 2). Modulation of the ligand from XPhos to SPhos resulted
in higher yields and a small increase in diastereoselectivity, provid-
ing diol 4a in a modest 62 : 38 diastereoselectivity. The use of more
sterically encumbered substrates, such as tert-butyl derivative 1b,
afforded excellent diastereoselectivity with 4b being formed in 95 : 5
diastereoselectivity, with the anti diastereoisomer predominating.
We thank Queen’s University Belfast and the EPSRC for funding
The Department of Employment and Learning, Northern Ireland
are also thanked for a studentship (MGM).
References
1 Y. Nakao and T. Hiyama, Chem. Soc. Rev., 2011, 40, 4893.
2 G. R. Jones and Y. Landais, Tetrahedron, 1996, 52, 7599.
3 E. A. Ilardi, C. E. Stivala and A. Zakarian, Org. Lett., 2008, 10, 1727.
4 A. K. Franz and S. O. Wilson, J. Med. Chem., 2013, 56, 388.
5 For reviews see: (a) I. Fleming, A. Barbero and D. Walter, Chem. Rev.,
1997, 97, 2063; (b) B. Marciniec, Hydrosilylation in Advances in Silicon
Science, Springer Science, 2009; For recent examples see: (c) G. Berthon-
(1)
´
Gelloz, J.-M. Schumers, G. De Bo and I. N. E. Marko, J. Org. Chem., 2008,
73, 4190; (d) A. M. Tondreau, C. C. H. Atienza, K. J. Weller, S. Nye,
K. M. Lewis, J. G. P. Delis and P. J. Chirik, Science, 2012, 335, 567;
(e) B. J. Truscott, A. M. Slawin and S. P. Nolan, Dalton Trans., 2013,
42, 270.
6 (a) J. L. Speier, J. A. Webster and G. H. Barnes, J. Am. Chem. Soc.,
1957, 79, 974; (b) J. C. Saam and J. L. Speier, J. Am. Chem. Soc., 1958,
80, 4104; (c) Reviews: B. Marciniec, Advances in Silicon Science,
Springer Science, 2009; (d) D. Troegel and J. Stohrer, Coord. Chem.
Rev., 2011, 255, 1440.
The stereochemical model for the observed reactivity is high-
lighted in Fig. 1. As was mentioned earlier we believe that Et2NSi-
Me2H performs an intramolecular hydrosilylation reaction through
the intermediacy of a silyl ether analogous to what had previously
been reported by Tamao and Ito,10 albeit with significantly higher
stereocontrol. The molecule is constrained with the oxygen func-
tionality on the same side as the incoming Pt–H bond. The
stereoselectivity is therefore determined by the minimization of
A1,2 strain between the R2 group and either a hydrogen or R1
7 B. D. Karstedt, France Pat., FR1548775, 1968.
8 (a) Y. Kiso, K. Yamamoto, K. Tamao and M. Kumada, J. Am. Chem.
Soc., 1972, 94, 4373; (b) Y. Uozumi and T. Hiyashi, J. Am. Chem. Soc.,
1991, 113, 9887; (c) Y. Uozumi, S.-Y. Lee and T. Hiyashi, Tetrahedron
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 3501--3504 | 3503

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Lett., 1992, 33, 7185; (d) Y. Bo, S. Singh, H. Q. Duong, C. Cao and
S. M. Sieburth, Org. Lett., 2011, 13, 1787.
9 For Reviews see: (a) T. Hiyama and T. Kusumoto, in Comprehensive
Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press,
Oxford, 1991, vol. 8, p. 763; (b) B. Marciniec, J. Gulinski, W. Urbaniac
and Z. W. Kornetka, Comprehensive Handbook on Hydrosilylation,
S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 11818; (c) R. Tundel,
T. Ikawa, R. Altman and S. L. Buchwald, Angew. Chem., Int. Ed., 2006,
45, 6523; (d) T. Kinzel, Y. Zhang and S. L. Buchwald, J. Am. Chem.
Soc., 2010, 132, 14073; (e) P. J. Milner, T. J. Maimone, M. Su, J. Chen,
P. Mu¨ller and S. L. Buchwald, J. Am. Chem. Soc., 2012, 134, 19922;
( f ) M. A. Oberli and S. L. Buchwald, Org. Lett., 2012, 14, 4606.
Pergamon, Oxford, UK, 1992; (c) I. Ojima, Z. Y. Li and J. W. Zhu, 15 (a) I. Paterson, Pure Appl. Chem., 1992, 64, 1821; (b) C. Marchionni
in Chemistry of Organosilicon Compounds, ed. Z. Rappaport and
Y. Apeloig, John Wiley & Sons Ltd, England, 1998, vol. 2, p. 1687.
and P. Vogel, Helv. Chim. Acta, 2001, 84, 431; (c) I. Patterson and
A. D. Findlay, Aust. J. Chem., 2009, 62, 624.
10 K. Tamao, T. Nakajima, R. Sumiya, H. Arai, N. Higuchi and Y. Ito, 16 For early review see: (a) M. Kim, S. F. Williams and S. Masamune,
J. Am. Chem. Soc., 1986, 108, 6090.
in Comprehensive Organic Synthesis 2, ed. B. M. Trost and I. Fleming,
Pergamon Press, Oxford, 1991, p. 239; for early examples see:
(b) H. C. Brown, R. K. Dhar, R. K. Bakshi, P. K. Pandiarajan and
B. Singaram, J. Am. Chem. Soc., 1989, 111, 3441; (c) I. Paterson,
J. M. Goodman, M. A. Lister, R. C. Schumann, C. K. McClure and
R. D. Norcross, Tetrahedron, 1990, 46, 4663; (d) D. A. Evans, H. P. Ng,
J. S. Clark and D. L. Rieger, Tetrahedron, 1992, 48, 2127; for recent
examples see: (e) H. Kim, S. Ho and J. L. Leighton, J. Am. Chem. Soc.,
2011, 133, 6517; ( f ) M. Chem and W. R. Roush, J. Org. Chem., 2013,
78, 3, and references therein.
11 For syn selective rhodium catalysed hydroboration/oxidations see:
(a) D. A. Evans, G. C. Fu and A. H. Hoyveda, J. Am. Chem. Soc., 1988,
110, 6917; (b) K. Burgess and M. J. Ohlmeyer, Tetrahedron Lett., 1989,
30, 395.
12 (a) S. A. Powell, J. M. Tenenbaum and K. A. Woerpel, J. Am. Chem.
Soc., 2002, 124, 12648; (b) F. Li and W. R. Roush, Org. Lett., 2009,
11, 2932; (c) G. Berthon-Gelloz, J.-M. Schumers, G. De Bo and
´
I. E. Marko, J. Org. Chem., 2008, 73, 4190.
13 For hydrosilylation of propargylic alcohols see: (a) M. G. McLaughlin
and M. J. Cook, Chem. Commun., 2011, 47, 11104; (b) C. A. McAdam, 17 X. Gao, H. Han and M. J. Krische, J. Am. Chem. Soc., 2011, 133, 12795.
+
M. G. McLaughlin, A. J. S. Johnston, J. Chen, M. W. Walter and 18 D. Kashin, A. Meyer, R. Wittenberg, K.-U. Schoning, S. Kamlage and
M. J. Cook, Org. Biomol. Chem., 2013, 11, 4488, for uses see;
A. Kirshning, Synthesis, 2007, 304.
(c) M. G. McLaughlin and M. J. Cook, J. Org. Chem., 2012, 19 (a) J. Cossy, N. Blanchard and C. Meyer, Org. Lett., 2001, 3, 2567;
77, 2058; (d) A. J. S. Johnston, M. G. McLaughlin, J. P. Reid and
M. J. Cook, Org. Biomol. Chem., 2013, 11, 7662.
14 For review see: (a) D. S. Surry and S. L. Buchwald, Chem. Sci., 2011,
(b) J. Cossy, N. Blanchard and C. Meyer, Tetrahedron Lett., 2002,
43, 1801; (c) C. Meyer, N. Blanchard, M. Defosseux and J. Cossy,
Acc. Chem. Res., 2003, 36, 766.
2, 27; For examples see: (b) H. N. Nguyen, X. Huang and 20 N. T. Ahn and O. Eisenstein, Nouv. J. Chim., 1977, 1, 61.
3504 | Chem. Commun., 2014, 50, 3501--3504
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