Enantioselective syntheses of syn-β-and anti-a- Hydroxyallylsilanes via allene hydroboration-Aldehyde allylboration reactions

Article abstract of DOI:10.1021/ol200392u

The kinetic hydroboration of allenylsilane 5 with (dIpc)2BH at -40°C provides allylborane 9Z with >12:1 selectivity. When the hydroboration is performed at temperatures above -40°C, 9Z isomerizes to the thermodynamically more stable allylborane 9E with>20:1 selectivity. Subsequent treatment of 9Z or 9E with aldehydes at -78°C provides syn- or anti-a-hydroxyallylsilanes, 7 or 8, respectively

Full text of DOI:10.1021/ol200392u

ORGANIC
LETTERS
2011
Vol. 13, No. 8
1992–1995
Enantioselective Syntheses of syn- and
anti-β-Hydroxyallylsilanes Via Allene
Hydroboration-Aldehyde Allylboration
Reactions
Ming Chen and William R. Roush*
Department of Chemistry, Scripps Florida, Jupiter, Florida 33458, United States
roush@scripps.edu
Received February 11, 2011
ABSTRACT
The kinetic hydroboration of allenylsilane 5 with (dIpc)2BH at -40 °C provides allylborane 9Z with g12:1 selectivity. When the hydroboration is
performed at temperatures above -40 °C, 9Z isomerizes to the thermodynamically more stable allylborane 9E with >20:1 selectivity. Subsequent
treatment of 9Z or 9E with aldehydes at -78 °C provides syn- or anti-β-hydroxyallylsilanes, 7 or 8, respectively.
Syn- and anti-β-hydroxyallylsilanes are versatile and
important building blocks in organic synthesis1 and have
been used in syntheses of a variety of natural products.2,3
Consequently, extensive efforts have been devoted to the
stereocontrolled synthesis of β-hydroxyallylsilanes.4-6
Aldehyde allylation using γ-silylallylmetal reagents is
the most widely adopted procedure for the synthesis
of anti-β-hydroxyallylsilanes.7,8 Several enantioselective
γ-silylallylboron5 and titanium6a,b reagents have been
developed. More recently, an important advance in the
catalytic asymmetric synthesis of anti-β-hydroxyallylsi-
lanes has also been achieved.6c However, compared to
the methods available to prepare anti-β-hydroxyallylsilanes,
(1) (a) Fleming, I. Org. React. 1989, 37, 57. (b) Masse, C. E.; Panek,
J. S. Chem. Rev. 1995, 95, 1293. (c) Fleming, I.; Barbero, A.; Walter, D.
Chem. Rev. 1997, 97, 2063. (d) Chabaud, L.; James, P.; Landais, Y. Eur.
J. Org. Chem. 2004, 3173. (e) Bates, R. H.; Chen, M.; Roush, W. R. Curr.
Opin. Drug Discovery Dev. 2008, 11, 778.
(2) (a) Sparks, M. A.; Panek, J. S. J. Org. Chem. 1991, 56, 3431. (b)
Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113, 9868. (c) Huang, H.;
Panek, J. S. J. Am. Chem. Soc. 2000, 122, 9836. (d) Wu, J.; Chen, Y.;
Panek, J. S. Org. Lett. 2010, 12, 2112. For recent applications: (e) Zhang,
Y.; Panek, J. S. Org. Lett. 2009, 11, 3366. (f) Wrona, I. E.; Gozman, A.;
Taldone, T.; Chiosis, G.; Panek, J. S. J. Org. Chem. 2010, 75, 2820.
(3) (a) Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999, 64, 1434.
(b) Smitrovich, J. H.; Woerpel, K. A. Synthesis 2002, 2778. (c) Romero,
A.; Woerpel, K. A. Org. Lett. 2006, 8, 2127. (d) Leonard, N. M.;
Woerpel, K. A. J. Org. Chem. 2009, 74, 6915.
(4) (a) Chan, T. H.; Wang, D. Chem. Rev. 1995, 95, 1279. (b)
Lombardo, M.; Trombini, C. Chem. Rev. 2007, 107, 3843 and references
cited therein. (c) Yamamoto, Y.; Saito, Y.; Maruyama, K. J. Chem. Soc.,
Chem. Commun. 1982, 1326. (d) Reetz, M. T.; Wenderoth, B. Tetra-
hedron Lett. 1982, 23, 5259. (e) Ikeda, Y.; Yamamoto, H. Bull. Chem.
Soc. Jpn. 1986, 59, 657. (f) Landais, Y.; Mahieux, C.; Schenk, K.;
Surange, S. S. J. Org. Chem. 2003, 68, 2779.
(5) For examples of enantioselective synthesis of β-hydroxyallylsi-
lanes using γ-silylallylboron reagents: (a) Roush, W. R.; Grover, P. T.;
Lin, X. Tetrahedron Lett. 1990, 31, 7563. (b) Barrett, A. G. M.; Malecha,
J. W. J. Org. Chem. 1991, 56, 5243. (c) Hunt, J. A.; Roush, W. R.
Tetrahedron Lett. 1995, 36, 501. (d) Roush, W. R.; Pinchuk, A. N.;
Micalizio, G. C. Tetrahedron Lett. 2000, 41, 9413. (e) Lira, R.; Roush,
W. R. Org. Lett. 2007, 9, 4315. (f) Kister, J.; DeBaillie, A. C.; Lira, R.;
Roush, W. R. J. Am. Chem. Soc. 2009, 131, 14174. (g) Binanzer, M.;
Fang, G. Y.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2010, 49, 4264. (h)
Robinson, A.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2010, 49, 6673.
(6) For other examples of enantioselective synthesis of β-hydroxyal-
lylsilanes using γ-silylallylmetal reagents, see: (a) Hafner, A.; Duthaler,
R. O.; Marti, R.; Rihs, G.; Rothe-Streit, P.; Schwarzenbach, F. J. Am.
Chem. Soc. 1992, 114, 2321. (b) Adam, J.-M.; Fays, L.; Laguerre, M.;
Ghosez, L. Tetrahedron 2004, 60, 7325. (c) Han, S. B.; Gao, X.; Krische,
M. J. J. Am. Chem. Soc. 2010, 132, 9153.
r
10.1021/ol200392u
Published on Web 03/16/2011
2011 American Chemical Society

stereoselective synthesis of the diastereomeric syn-β-hy-
droxyallylsilane isomers, and especially enantioselective
syntheses of the syn isomers,5e,7f largely remains an un-
solved problem due to the facile isomerization of (Z)- and
(E)-γ-silylallylmetal reagents.4,9,10 Therefore, develop-
ment of a stereocontrolled method for synthesis of chiral,
nonracemic (Z)-γ-silylallylmetal reagents and the corre-
sponding syn-β-hydroxyallylsilanes via enantioselective
aldehyde allylation remains an important goal. Accord-
ingly, we have developed and report herein a simple, one
step, diastereo- and enantioselective synthesis of syn-β-
hydroxyallylsilanes via a highly stereoselective allene hy-
droboration-aldehyde allylboration reaction sequence.
We recently reported that hydroboration of allenylstan-
nane 1 with diisopinocampheylborane [(dIpc)2BH] initially
forms (Z)-γ-stannylallylborane 2 as the kinetic product,
and that 2 isomerizes rapidly through a highly diastereo-
selective 1,3-boratropic shift to give the thermodynami-
cally stable R-stannylallylborane 3 (eq 1, Figure 1).11d
Subsequent allylboration of aldehydes with 3 gave (E)-
δ-stannyl-homoallylic alcohols 4 in good yields and
excellent enantioselectivities. With the objective to
synthesize the potentially environmentally benign (E)-
δ-silyl-homoallylic alcohols 6, we decided to study the
hydroboration of allenylsilane 512 (eq 2, Figure 1).
Figure 1. Hydroboration of allenylstannane 1 and planned
hydroboration of allenylsilane 2 with (dIpc)2BH.
In initial experiments, treatment of allenylsilane 5 with
(dIpc)2BHintoluene at-40°C for5 h followedbyaddition
of hydrocinnamaldehyde at -78 °C provided the β-hydro-
xyallylsilane 7a in 76% yield, 87% ee, and 14:1 d.s. and not
the originally targeted homoallylic alcohol 6(entry 1, Table 1).
1
After careful comparison of the H NMR spectra of the
reaction product with the data reported in the literature for
7a,5e,7f the major product was determined to be the syn-
β-hydroxyallylsilane diastereomer (7a). The minor pro-
duct is the anti- isomer 8a. Application of this procedure to
the (Z)-γ-silylallylboration of a variety of other aldehydes
(entries 2-6, Table 1) provided syn-β-hydroxyallylsilanes
7b-7f in 67-80% yields with g12:1 diastereoselectivities
and 84-87% ee. The absolute stereochemistry of the
secondary hydroxyl groups of 7a-7f were assigned by
using the modified Mosher ester analysis.13 The regioiso-
meric (E)-δ-silyl-homoallylic alcohols 6 were not observed
in these experiments.
(7) For selected synthetic applications of β-hydroxyallylsilanes: (a)
Micalizio, G. C.; Roush, W. R. Org. Lett. 2000, 2, 461. (b) Roush, W. R.;
Dilley, G. J. Synlett 2001, 955. (c) Heo, J.-N.; Micalizio, G. C.; Roush,
W. R. Org. Lett. 2003, 5, 1693. (d) Shotwell, J. B.; Roush, W. R. Org.
Lett. 2004, 6, 3865. (e) Tinsely, J. M.; Roush, W. R. J. Am. Chem. Soc.
2005, 127, 10818. (f) Tinsley, J. M.; Mertz, E.; Chong, P. Y.; Rarig, R.-A.
F.; Roush, W. R. Org. Lett. 2005, 7, 4245. (g) Mertz, E.; Tinsley, J. M.;
Roush, W. R. J. Org. Chem. 2005, 70, 8035. (h) Va, P.; Roush, W. R. J.
Am. Chem. Soc. 2006, 128, 15960. (i) Huh, C. W.; Roush, W. R. Org.
Lett. 2008, 10, 3371.
(8) For other selected applications of β-hydroxyallylsilanes: (a) Pa-
terson, I.; Findlay, A. D.; Anderson, E. A. Angew. Chem., Int. Ed. 2007,
46, 6699. (b) Kishi, N.; Maeda, T.; Mikami, K.; Nakai, T. Tetrahedron
1992, 48, 4087. (c) Vincent, G.; Mansfield, D. J.; Vors, J.-P.; Ciufolini,
M. A. Org. Lett. 2006, 8, 2791. (d) Beignet, J.; Jervis, P. J.; Cox, L. R. J.
Org. Chem. 2008, 73, 5462. (e) Peroche, S.; Remuson, R.; Gelas-Mialhe,
Y.; Gramain, J. C. Tetrahedron Lett. 2001, 42, 4617. (f) Ducray, R.;
Ciufolini, M. A. Angew. Chem., Int. Ed. 2002, 41, 4688.
The diastereoselectivity of this reaction sequence proved
to be highly dependent on experimental conditions. When
the hydroboration of 5 was performed at -20 °C followed
by addition of hydrocinnamaldehyde at -78 °C, a 2:1
mixture of syn- and anti-β-hydroxyallylsilanes 7a and 8a
was obtained in 81% yield. Similarly, when the hydro-
boration step was carried out at-30°C, a 3:1 mixture of 7a
and 8a was obtained in 77% yield. Hydroboration of 5 at
-40 °C for 12 h also led to the formation of a 5:1 mixture
of 7a and 8a. When the hydroboration step was carried
out at temperatures below -40 °C (e.g., -50 °C for 5 h),
the subsequent allylboration of hydrocinnamaldehyde at
-78 °Cprovided7a as the only product, albeit in diminished
yield (24%), owing to incomplete allene hydroboration.
These results indicate thatat temperaturesbelow -40°C
the kinetic hydroboration adduct 9Z, produced in the reac-
tion of 5 with (dIpc)2BH, does not rapidly isomerize to the
thermodynamically more stable allylborane 9E (Scheme 1).
While the 1,3-boratropic shifts of the (dIpc)2B- group is
known to be slow for γ,γ-disubstituted allylboranes,11b
this kinetically controlled hydroboration of allenylsilane 5
represents a rare case that a (Z)-γ-substituted allylborane
(9) (a) Hancock, K. G.; Kramer, J. D. J. Am. Chem. Soc. 1973, 95,
6463. (b) Kramer, G. W.; Brown, H. C. J. Organomet. Chem. 1977, 132,
9. (c) Hoffmann, R. W.; Zeiss, H. J. J. Org. Chem. 1981, 46, 1309. (d)
Henriksen, U.; Snyder, J. P.; Halgren, T. A. J. Org. Chem. 1981, 46,
3767. (e) Brown, H. C.; Jadhav, P. K.; Bhat, K. S. J. Am. Chem. Soc.
1985, 107, 2564. (f) Wang, K. K.; Gu, Y. G.; Liu, C. J. Am. Chem. Soc.
1990, 112, 4424. (g) Gu, Y. G.; Wang, K. K. Tetrahedron Lett. 1991, 32,
3029. (h) Brown, H. C.; Narla, G. J. Org. Chem. 1995, 60, 4686. (i) Narla,
G.; Brown, H. C. Tetrahedron Lett. 1997, 38, 219. (j) Fang, G. Y.;
Aggarwal, V. K. Angew. Chem.; Int. Ed. 2007, 46, 359. (k) Canales, E.;
ꢀ
Gonzalez, A. Z.; Soderquist, J. A. Angew. Chem.; Int. Ed. 2007, 46, 397.
ꢀ
ꢀ
(l) Gonzalez, A. Z.; Roman, J. G.; Alicea, E.; Canales, E.; Soderquist,
J. A. J. Am. Chem. Soc. 2009, 131, 1269.
(10) One notable exception to the rapid isomerization of (Z)-and (E)-
crotylborane isomers has been reported by Soderquist: Burgos, C. H.;
Canales, E.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc. 2005, 127,
8044. Also see ref 5f.
(11) (a) Flamme, E. M.; Roush, W. R. J. Am. Chem. Soc. 2002, 124,
13644. (b) Chen, M.; Handa, M.; Roush, W. R. J. Am. Chem. Soc. 2009,
131, 14602. (c) Ess, D. H.; Kister, J.; Chen, M.; Roush, W. R. Org. Lett.
2009, 11, 5538. (d) Chen, M.; Ess, D. H.; Roush, W. R. J. Am. Chem. Soc.
2010, 132, 7881. (e) Stewart, P.; Chen, M.; Roush, W. R.; Ess, D. Org.
Lett. 201110.1021/ol2001599. (f) Kister, J.; Nuhant, P.; Lira, R.; Sorg, A.;
Roush, W. R. Org. Lett. 2011, in press.
(12) (a) Myers, A. G.; Zheng, B. Org. Synth. 1999, 76, 178. (b) Li, Z.;
Yang, C.; Zheng, H.; Qiu, H; Lai, G. J. Organomet. Chem. 2008, 693,
3771. (c) Fandrick, D. R.; Reeves, J. T.; Tan, Z.; Lee, H.; Song, J. J.; Yee,
N. K.; Senanayake, C. H. Org. Lett. 2009, 11, 5458.
(13) (a) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512. (b)
Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc.
1991, 113, 4092.
Org. Lett., Vol. 13, No. 8, 2011
1993

isomerization-allylboration sequence was applied to a
variety of aldehydes (Table 2). In all cases, anti-β-hydro-
xyallylsilanes 8a-f were obtained in 80-91% yield and
83-87% ee with >20:1 diastereoselectivity.
Table 1. Synthesis of syn-β-Hydroxyallylsilanes 7 via Kineti-
cally Controlled Hydroboration of Allenylsilane 5a
To gain insight into the proposed reaction pathways, we
1
carried out H NMR studies of the hydroboration of
allenylsilane 5 with (dIpc)2BH at -20 and 0 °C.14 As
Table 2. Synthesis of anti-β-Hydroxyallylsilanes 8 via Allene
entry
RCHO
product
yield
d.s.
% eeb
Hydroboration and Allylborane Isomerizationa
1
2
3
4
5
6
Ph(CH2)2CHO
PhCH2CHO
PhCHO
7a
7b
7c
7d
7e
7f
76%
70%
80%
67%
71%
72%
14:1
12:1
18:1
20:1
15:1
14:1
87
87
86
84
84
87
CyCHO
TBSO(CH2)2CHO
TBSOCH2CHO
a Reactions were performed by treating 5 with (dIpc)2BH (0.9 equiv)
in toluene at -40 °C for 5 h, followed by the addition of RCHO (0.8
equiv) at -78 °C. The mixture was then allowed to stir at -78 °C for 12 h.
The reactions were subjected to a standard workup (NaHCO3, H2O2) at
0 °C prior to product isolation. b Determined by Mosher ester analysis.13
entry
RCHO
product yield
d.s.
% eeb
1
2
3
4
5
6
Ph(CH2)2CHO
PhCH2CHO
PhCHO
8a
8b
8c
8d
87%
90%
83%
80%
91%
87%
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
86
87
83
86
85
84
CyCHO
can be obtained in good Z/E ratio via hydroboration of a
monosubstituted allene with dialkylboranes such as
(Ipc)2BH. Most (Z)-crotylboranes are configurationally
unstable at temperatures above -60 °C.9b Allylboranes in-
corporating the Soderquist borane (10-TMS-9-bora-
bicyclo[3.3.2]decanyl) auxiliary constitute the only general
exception.10
TBDPSO(CH2)2CHO 8e
TBSOCH2CHO 8f
a Reactions were performed by treating 5 with (dIpc)2BH (0.9 equiv)
in toluene at -40 °C and warmed to 0 °C over 5 h, followed by the
addition of RCHO (0.8 equiv) at -78 °C. The mixture was then allowed
to stir at -78 °C for 12 h. The reactions were subjected to a standard
workup (NaHCO3, H2O2) at 0 °C prior to product isolation. b Deter-
mined by Mosher ester analysis.13
illustrated in Figure 2, hydroboration of 5 with (dIpc)2BH
at -20 °C initially generates (Z)-γ-silylallylborane 9Z (J =
12.8 Hz). Allylborane 9Z isomerizes at -20 °C (monitored
over 150 min) to (E)-γ-silylallylborane 9E (J = 18.4 Hz).
This isomerization is complete in about 60 min when the
reaction mixture is allowed to warm to 0 °C. The fleeting
intermediate R-silylallylborane 10 was not observed during
these experiments.
Scheme 1. Proposed Kinetic Hydroboration of 5 and Thermo-
dynamically Controlled Allylborane Isomerization
Strikingly, while the hydroboration of allenylstannane 1
with (dIpc)2BH provides R-stannylallylborane 3 as the
most stable component of the equilibrating mixture,15
the resting state of the hydroboration of allenylsilane 5 is
(Z)- or (E)-γ-silylallylboranes, 9Z or 9E, depending on the
temperature of the hydroboration (Figure 3). Although it
is well-known that both R3Si- and R3Sn- can stabilize a
β-carbocation,16 the capacity of these two groups to
stabilize the β-carbocation is clearly different. For the
intermediate R-stannylallylborane 3, the hyperconjugative
interaction between the Bu3Sn- group and the boron
As shown in Scheme 1, the kinetic adduct 9Z can iso-
merize to the more stable allylborane 9E through a rever-
sible 1,3-boratropic shift9,11 at temperatures above -40 °C,
presumably via the intermediacy of 10. Subsequent allyl-
boration of aldehydes with 9E should allow access to the
diastereomeric anti-β-hydroxyallylsilanes8(whichwehave
previously demonstrated by an alternative method).5d
Indeed, when the hydroboration of allenylsilane 5 was
performed at -40 °C with the solution being allowed to
warm to 0 °C over 5 h, addition of hydrocinnamaldehyde
to the resulting allylborane at -78 °C provided anti-
β-hydroxyallylsilanes 8a with >20:1 dr (8a:7a) in 87%
yield and 86% ee (Table 2, entry 1). The hydroboration-
(14) We were not able to perform NMR studies at -40 °C due to the
low solubility of (dIpc)2BH in d8-toluene at this temperature. (dIpc)2BH
is not fully soluble even at -20 °C, consequently signal resolution is poor
at early stages of the reaction.
(15) See SI1 of ref 11d for details.
(16) (a) Davis, D. D.; Gray, C. E. J. Org. Chem. 1970, 35, 1303. (b)
Jerkunica, J. M.; Traylor, T. G. J. Am. Chem. Soc. 1971, 93, 6278. (c)
Wierschke, S. G.; Chandrasekhar, J.; Jorgensen, W. L. J. Am. Chem.
Soc. 1985, 107, 1496. (d) Lambert, J. B.; Wang, G. T.; Finzel, R. B. J.
Am. Chem. Soc. 1987, 109, 7838. (e) Lambert, J. B.; Wang, G. T.;
Teramura, D. H. J. Org. Chem. 1988, 53, 5422.
1994
Org. Lett., Vol. 13, No. 8, 2011

atom (isoelectronic to a carbocation) must be strong
enough to override the steric repulsion between the
Bu3Sn- and the (dIpc)2B- units.11e The relatively long
Sn-C bond(2.20A in3)11e might alsobebeneficial. Onthe
˚
other hand, for the intermediate R-silylallylborane 10, it
appears that the steric repulsion between the PhMe2Si-
group and the (dIpc)2B- unit overrides the hyperconjuga-
tive stabilization.11e The relatively shorter Si-C bond
˚
(estimated to be 1.85 A) and the size of PhMe2Si- group
presumably contribute to the steric effect, such that 9Z or
9E are much more stable than 10. These conclusions are
supported by a recent computational study.11e
Figure 3. Comparison of the hydroboration-isomerization
pathways for allenylstannane 1 and allenylsilane 5.
temperatures below -40 °C, the hydroboration reaction
proceeds under kinetic control to give 9Z with good
selectivity. The normally facile 1,3-boratropic shift9 is slow
at-40°Cinthecaseof9Z. However, isomerizationreadily
occurs at temperatures above -40 °C, and complete iso-
merization of 9Z to 9E is observed at 0 °C. Thus, by
appropriate control of the hydroboration conditions,
highly diastereo- and enantioselective syntheses of either
syn- or anti-β-hydroxyallylsilanes, 7 or 8, can be achieved
via aldehyde allylboration reaactions of 9Z and 9E,
respectively.
Acknowledgment. Financial support provided by the
National Institutes of Health (GM038436) is gratefully
acknowledged.
Figure 2. 1H NMR studies of hydroboration of allenylsilane 5 in
d8-toluene. 1H resonances in the olefinic region (8-5.5 ppm) are
displayed in the partial spectra.
Supporting Information Available. Experimental pro-
cedures and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, we have developed stereoselective synth-
eses of (Z)- and (E)-γ-silylallylboranes 9Z and 9E via
hydroboration of allenylsilane 5 with (dIpc)2BH. At
Org. Lett., Vol. 13, No. 8, 2011
1995