Asymmetric synthesis of tertiary and quaternary allyl- and crotylsilanes via the borylation of lithiated carbamates

Article abstract of DOI:10.1021/ol200177f

Tertiary allyl- or crotylsilanes have been prepared in high er and dr via the lithiation-borylation reaction of alkyl carbamates with silaboronates. Using a related strategy, quaternary allylsilanes could be accessed in similarly high er.

Full text of DOI:10.1021/ol200177f

ORGANIC
LETTERS
2011
Vol. 13, No. 6
1490–1493
Asymmetric Synthesis of Tertiary and
Quaternary Allyl- and Crotylsilanes via
the Borylation of Lithiated Carbamates
Varinder K. Aggarwal,* Michael Binanzer, M. Carolina de Ceglie, Maddalena Gallanti,
Ben W. Glasspoole, Stephanie J. F. Kendrick, Ravindra P. Sonawane,
ꢀ
Ana Vazquez-Romero, and Matthew P. Webster
School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K.
v.aggarwal@bristol.ac.uk
Received January 20, 2011
ABSTRACT
Tertiary allyl- or crotylsilanes have been prepared in high er and dr via the lithiation-borylation reaction of alkyl carbamates with silaboronates.
Using a related strategy, quaternary allylsilanes could be accessed in similarly high er.
Allylsilanes are highly versatile synthetic intermedi-
ates which have been used extensively in complex
molecule synthesis.1 As such, methods to generate
allylsilanes in high enantiomeric and diastereomeric
purity have attracted widespread attention from the
synthetic community.2-8
Methods for the preparation of tertiary allylsilanes have
included Cu-catalyzed allylic alkylation2,3 and carbonyl
allylation.4 Methods for the preparation of the more
challenging quaternary allylsilanes have included the
hydroboration5 or hydrozirconation6 of allenylsilanes fol-
lowed by addition to aldehydes or imines, Claisen rearran-
gement of vinyl silanes,7 Cu-catalyzed asymmetric allylic
alkylation,2 and enantioselective allylic substitution.8
While many of these methods provide efficient pathways
to specific allylsilanes, general strategies to allylsilanes in
high er and dr, particularly in the case of crotylsilanes,
remain underdeveloped.
(1) (a) Masse, C. E.; Panek, J. S. Chem. Rev. 1995, 95, 1293–1316. (b)
Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063–2192. (c)
Sarkar, T. K. In Science of Synthesis, Houben-Weyl Methods of Mole-
cular Transformations; Fleming, I., Ed.; Thieme: Stuttgart, 2002; Vol. 4, pp
837-926.
(2) Kacprzynski, M. A.; May, T. L.; Kazane, S. A.; Hoveyda, A. H.
Angew. Chem., Int. Ed. 2007, 46, 4554–4558.
(3) (a) Schmidtmann, E. S.; Oestreich, M. Chem. Commun. 2006,
3643–3645. (b) Vyas, D. J.; Oestreich, M. Angew. Chem., Int. Ed. 2010,
49, 8513–8515.
(4) Han, S. B.; Gao, X.; Krische, M. J. J. Am. Chem. Soc. 2010, 132,
9153–9156.
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4424–4431. (b) Heo, J.-N.; Micalizio, G. C.; Roush, W. R. Org. Lett.
2003, 5, 1693–1696. (c) Lambert, W. T.; Roush, W. R. Org. Lett. 2005, 7,
5501–5504.
(6) Wipf, P.; Pierce, J. G. Org. Lett. 2005, 7, 3537–3540.
(7) Lowe, J. T.; Panek, J. S. Org. Lett. 2005, 7, 1529–1532.
(8) Gao, F.; McGrath, K. P.; Lee, Y.; Hoveyda, A. H. J. Am. Chem.
Soc. 2010, 132, 14315–14320.
(9) An alternative to Zweifel olefination is Suzuki-Miyaura cross-
coupling of boronate esters with vinyl halides. However, whilst
1,1-silaboronic acid, Me3SiCH2B(OH)2, couples with vinyl halides to
give allylsilanes [see: (a) Zou, G.; Reddy, Y. K.; Falck, J. R. Tetrahedron
Lett. 2001, 42, 7213–7215.] the more substituted 1,1-silaboronic acid
pinacol esters do not [see:(b) Endo, K.; Ohkubo, T.; Hirokami, M.;
Shibata, T. J. Am. Chem. Soc. 2010, 132, 11033–11035.] and so this
strategy cannot be used to make tertiary or quaternary allylsilanes. Endo
et al. did report the successful coupling of substituted 1,1-bisboronic acid
pinacol esters. Apart from this and other isolated cases, secondary
boronic acids/pinacol esters do not normally undergo efficient Suzuki-
Miyaura cross-coupling. For a review, see: (c) Crudden, C. M.; Glasspoole,
B. W.; Lata, C. J. Chem. Commun. 2009, 6704–6716.
(10) (a) Zweifel, G.; Arzoumanian, H.; Whitney, C. C. J. Am. Chem.
Soc. 1967, 89, 3652–3653. (b) Evans, D. A.; Crawford, T. C.; Thomas,
R. C.; Walker, J. A. J. Org. Chem. 1976, 41, 3947–3953. (c) Matteson,
D. S. In The Chemistry of the Metal-carbon Bond, Hartley, F. R., Ed.;
Wiley: 1987; Vol. 4, pp 307-499 and references therein. (d) Matteson,
D. S. Chem. Rev. 1989, 89, 1535–1551.
r
10.1021/ol200177f
Published on Web 02/18/2011
2011 American Chemical Society

Scheme 1. Proposed Synthesis of Tertiary Allylsilanesa
Scheme 2. Silaboration of Lithiated Carbamates 6
a Cb = 2,2-diisopropylcarbamoyl, sp = (-)-sparteine, pin =
pinacolato.
involving migration of the silyl group with expulsion of the
nucleofugal carbamate group, to furnish the 1,1-silabor-
onate 9. While the migration of a carbon substituent is
relatively common, there are only sporadic examples of the
migration of a silyl group.15 Nevertheless, this strategy
ultimately proved to be successful (Scheme 2). Lithiation
of carbamates 5, followed by the addition of the commer-
cially available boronate 7 and warming gave silaboro-
nates 9a and 9b in 69% and 68% yield, respectively.
Conditions for the Zweifel olefination10 had to be
modified to obtain good yields due to the sensitive nature
of the allylsilane product toward excess I2. In fact, we
found that I2/MeOH was superior to the more commonly
employed conditions of I2/NaOMe/MeOH. As illustrated
by the data summarized in Table 1, subsequent reaction of
boronate esters 9 with the alkenylmetal reagents 1016 at
-78 °C, followed by the addition of iodine in methanol,
gave allylsilanes 11 in excellent er (97:3-94:6) and good to
excellent yield (60-94%). Moreover, the dr was essentially
perfect for entries 2, 3, and 6, giving the respective crotyl-
silanes as single diastereomers by 1H NMR spectroscopy
(dr >25:1). Only in the case of the highly hindered
Z-crotylsilane 11e (entry 5) was the E-diastereomer visible
by NMR (85:15 dr in the crude material and 95:5 dr in the
isolated product). In this case, the minor E-olefin presum-
ably arises from the severe steric encumbrance of the
conformation required for anti-elimination (leading to
the Z-configuration) and so some syn-elimination occurs
which leads to the small amount of the E-isomer observed
(Scheme 3).17
Herein, we report two general strategies for the efficient
preparation of both tertiary and quaternary allylsilanes in high
er and dr using our lithiation-borylation method coupled
with Zweifel olefination of the derived boronate esters.9,10
We previously reported that enantioenriched lithiated alkyl
carbamates could react with boranes and boronate esters to
give their homologated counterparts in high er.11 This reaction
could even be applied to β-silyl vinylboranes, which led to an
asymmetric synthesis of β-hydroxy allylsilanes.11d,e Initial
studies (Scheme 1) aimed to extend this approach to the
synthesis of allylsilanes from R-silyl carbamate 1, however,
proved unrewarding, because the intermediate silyl-substituted
lithiated carbamate 2was configurationally unstable and led to
racemic allylsilane 4.12
We therefore considered an alternative approach: the
reaction of a configurationally stable, alkyl-substituted
lithiated carbamate 613 with silaboronate 7.14 This was
expected to give an intermediate ate-complex 8, which
would subsequently undergo 1,2-metalate rearrangement,
(11) (a) Stymiest, J. L.; Dutheuil, G.; Mahmood, A.; Aggarwal, V. K.
Angew. Chem., Int. Ed. 2007, 46, 7491–7494. (b) Stymiest, J. L.; Bagutski,
V.; French, R. M.; Aggarwal, V. K. Nature 2008, 456, 778–782. (c)
Dutheuil, G.; Webster, M. P.; Worthington, P. A.; Aggarwal, V. K.
Angew. Chem., Int. Ed. 2009, 48, 6317–6319. (d) Binanzer, M.; Fang,
G. Y.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2010, 49, 4264–4268. (e)
Robinson, A.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2010, 49, 6673–
ꢀ
6675. (f) Althaus, M.; Mahmood, A.; Suarez, J. R.; Thomas, S. P.;
Aggarwal, V. K. J. Am. Chem. Soc. 2010, 132, 4025–4028.
(12) Our attempts to effect the lithiation-borylation reaction, shown
in Scheme 1, only gave racemic allylsilane 4 (R = Ph) even when the
reaction was conducted at -100 °C. The configurational instability of
silyl-substituted lithiated carbamates has been noted before: (a) Simov,
B. P.; Rohn, A.; Brecker, L.; Giester, G.; Hammerschmidt, F. Synthesis
2004, 16, 2704–2710. (b) Schweifer, A.; Hammerschmidt, F. Tetrahedron
2008, 64, 7605–7610.
It should be noted that, in the case of boronate ester 9a
(R = PhCH2CH2), vinylmagnesium bromide was suffi-
ciently nucleophilic to effect ate-complex formation but,
for the more hindered boronate ester 9b (R = iPr), the
more reactive vinyllithium was required. Propenyllithium
compounds were used due to their ease of preparation
from the respective propenyl bromides by halogen-metal
exchange.16
(13) For reviews, see: (a) Hoppe, D.; Hense, T. Angew. Chem., Int.
€
Ed. Engl. 1997, 36, 2282–2316. (b) Hoppe, D.; Marr, F.; Bruggemann,
M. In Organolithiums in Enantioselective Synthesis; Hodgson, D. M., Ed.;
Springer-Verlag: Berlin, 2003; Vol. 5, pp 61-137 and references therein.
(c) Hoppe, D.; Christoph, G. In The Chemistry of Organolithium
Compounds; Rappoport, Z., Marek, I., Eds.; Wiley: Chichester, 2004;
Part 2, pp 1055-1164.
(14) Suginome, M.; Matsuda, T.; Ito, Y. Organometallics 2000, 19,
4647–4649. In addition to it being commercially available (and easy to
make according to the Suginome procedure), the UV chromophore
present makes it especially useful in determining er and therefore better
than the Me3Si analogue.
(15) (a) The silaboration has been pioneered by Buynak using ethyl
diazoacetate as the carbenoid: Buynak, J. D.; Geng, B. Organometallics
1995, 14, 3112–3115. (b) Hata, T.; Kitagawa, H.; Masai, H.; Kurahashi,
T.; Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 790–792.
(c) Shimizu, M.; Kurahashi, T.; Kitagawa, H.; Shimono, K.; Hiyama
T. J. Organomet. Chem. 2003, 686, 286–293.
(16) Preparation of vinyllithium: (a) Gassman, P. G.; Valcho, J. J.;
Proehl, G. S.; Cooper, C. F. J. Am. Chem. Soc. 1980, 102, 6519–6526.
Preparation of propenyllithium:(b) Neumann, H.; Seebach, D. Tetra-
hedron Lett. 1976, 52, 4839–4842. (c) See Supporting Information of:
ꢀ
€
Gerard, E. M. C.; Brase, S. Chem.;Eur. J. 2008, 14, 8086–8089.
(17) (a) Matteson, D. S.; Liedtke, J. D. J. Am. Chem. Soc. 1965, 87,
1526–1531. (b) Negishi, E.; Lew, G.; Yoshida, T. J. Org. Chem. 1974, 39,
2321–2322. (c) Slayden, S. W. J. Org. Chem. 1982, 47, 2753–2757. (d)
Matteson, D. S. Chem. Rev. 1989, 89, 1535–1551.
Org. Lett., Vol. 13, No. 6, 2011
1491

Table 1. Olefination of Silaboronates 9a
Scheme 3. Proposed Origin of the Minor E-Crotylsilane 11f
Table 2. Synthesis of Quaternary Allylsilanes 19a
a Reactions were performed on 0.2-1.0 mmol scales. Boronate ester
(1 equiv), alkenylmetal reagent (4 equiv), and methanolic I2 (4 equiv),
THF, -78 to 0 °C. b The alkenyllithium reagents were prepared from the
respective alkenyl bromides using 2 equiv of tBuLi (see Supporting
Information). c Yield of the isolated product. d The er was determined by
HPLC analysis, using a chiral stationary phase, of the products derived
from hydroboration/oxidation or from hydrogenation/Fleming-
Tamao oxidation (see Supporting Information). e Determined by ana-
lysis of 400 MHz 1H NMR spectra of the crude products. f Absolute
stereochemistry was assigned after comparison with the literature.2 All
other assignments were made by analogy. g The dr was determined after
column chromatography.
We were especially interested to see if we could extend
this method to the significantly more challenging quatern-
ary allylsilanes. To achieve this, we returned to the strategy
described in Scheme 1 since we recognized that secondary
silyl-substituted lithiated carbamates were configuration-
ally stable at low temperature.18 Our sequence commenced
with lithiation and silylation of carbamate 5a as previously
described (Table 2).18 Subsequent deprotonation with
sBuLi/TMEDA followed by the addition of a boronate
ester gave intermediates 18 with a unique 1,1-silaboronate
quaternary stereogenic center. These intermediates could
be either isolated in excellent yield (88-94% yield) or
subjected to the next transformation in situ without prior
workup. Brief optimization of the stoichiometry of the
reagents, temperature, and time provided a set of condi-
tions under which allylsilanes 19were obtainedin 62-75%
yield and very high er (97:3-98:2) from carbamates 14 in
one pot over two steps.
yield of 18 yield of 19
yield of 19
R1 R2
(%)b from 18 (%)b from 14 (one pot, %)b erc
1
2
3
4
Me Me 88d (18a)
Me Et 94 (18b)
Ph Me 52f (18c)
Ph Et 76 (18d)
68 (19a)
75 (19b)
98:2
97:3e
97:3
97:3
73 (19b)
73 (19c)
60 (19d)
62 (19d)
a Reagents and conditions: (i) sBuLi, TMEDA, Et2O, -78 °C, 5 h
then RMe2SiCl. (ii) R2Bpin, -78 to 23 °C or reflux. (iii) Vinyllithium
(2 equiv, prepared from tetravinyltin and nBuLi, THF, 0 °C), THF, 0 °C
then I2/MeOH. TMEDA = N,N,N0,N0-tetramethylethylenediamine.
b Yield of isolated product. c The er was determined by HPLC analysis,
using a chiral stationary phase, of the products derived from hydro-
boration/oxidation. d Racemic substrate was used for this reaction. e The
absolute stereochemistry was assigned by X-ray analysis of the alcohol
obtained from 19b by hydroboration/oxidation. All other assignments
were made by analogy (see Supporting Information for details). f MgBr2
was added to promote the 1,2-metalate rearrangement. Reflux condi-
tions led to partial racemization presumably due to reversibility of the
ate-complex formation.
Several points are worthy of note. (i) The one-pot
reaction gave a slightly higher yield compared to the
two-step procedure. (ii) The corresponding iPr substituted
substrate was sterically too hindered for deprotonation
with sBuLi under these conditions. (iii) For substrates 18,
the more reactive vinyllithium had to be used and the
(18) (a) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem., Int. Ed.
€
Hoppe, D. Eur. J. Org. Chem. 1998, 2397–2403.
Engl. 1993, 32, 394–396. (b) Behrens, K.; Frohlich, R.; Meyer, O.;
1492
Org. Lett., Vol. 13, No. 6, 2011

Scheme 4. Synthesis of ent-19c
Figure 1. X-ray structure of the alcohol obtained from hydro-
boration/oxidation of allylsilane 19b.
boronate ester ent-18c in excellent yield. Olefination with
vinyllithium and methanolic iodine gave allylsilane ent-19c
in 80% yield and 97:3 er.
temperature raised to 0 °C for efficient ate-complex for-
mation. The vinyl Grignard reagent only gave low conver-
sions. (iv) Reaction of 18withpropenyllithium reagents led
to incomplete formation of the ate-complex, presumably
due to the severe steric bulk of these 1,1-silaboronates.
(v) The absolute stereochemistry was determined by
X-ray analysis of the alcohol obtained by hydroboration/
oxidation of allylsilane 19b (see Figure 1 and Supporting
Information).19 (vi) This process could be extended to the
phenyldimethylsilyl group, enabling the incorporation of a
further synthetic handle.
One advantage of this approach is that either enantio-
mer of the intermediate boronate ester or the product
allylsilane can be obtained simply by switching the groups
on the carbamate and the boronate ester, thus obviating
the need to use the (þ)-sparteine surrogate.20 ent-19c was
synthesized starting from ethyl diisopropyl carbamate 20
(Scheme 4). Deprotonation using sBuLi/(-)-sparteine
followed by addition of phenyldimethylsilyl chloride
gave organosilane 21. Subsequent lithiation using sBuLi/
TMEDA followed by the addition of boronate ester 22a
gave, after 1,2-metalate rearrangement, the intermediate
The scope of the reaction was further exemplified in the
synthesis of allylsilane 24, bearing the ubiquitous prenyl
group, using the commercially available boronate ester
22b; excellent yields and er were observed throughout.
In summary, we have developed a simple method for the
synthesis of tertiary allyl- or crotylsilanes in high er and dr
using the lithiation-borylation reaction of alkyl carba-
mates with silaboronates. Using a related strategy, we have
developed a unique reaction sequence that leads to qua-
ternary allylsilanes in similarly high er.
Acknowledgment. We thank the EPSRC for support of
this work. V.K.A. thanks the Royal Society for a Wolfson
Research Merit Award and the EPSRC for a Senior
Research Fellowship. We thank Inochem - Frontier Scientific
for generous donation of boronic acids and boronate
esters. We thank Dr. Mairi Haddow (School of Chemistry
University of Bristol, UK) for X-ray analysis. B.W.G.
thanks Queen’s University for a Doctoral Travel Grant.
A.V.-R. thanks IRB Barcelona and MICINN for a travel
bursary.
(19) CCDC 800290 contains the supplementary crystallographic
data for the alcohol obtained from allylsilane 19b by hydroboration/
oxidation. This data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
Supporting Information Available. Experimental pro-
cedures and full spectroscopic data for all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(20) McGrath, M. J.; O’Brien, P. J. Am. Chem. Soc. 2005, 127,
16378–16379.
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