Enantio- and diastereoselective synthesis of syn-β-hydroxyallylsilanes via a chiral (Z)-γ-silylallylboronate

Article abstract of DOI:10.1021/ol7018746

syn-β-Hydroxyallylsilanes of general structure 11 and 28 are prepared in 50-86% yield and 91-95% ee (for aliphatic aldehydes; 50% ee for benzaldehyde) via the BF₃-Et₂O-promoted γ-silylallylboration reactions, using reagents 14 and 15.

Full text of DOI:10.1021/ol7018746

ORGANIC
LETTERS
2007
Vol. 9, No. 21
4315-4318
Enantio- and Diastereoselective
Synthesis of syn- -Hydroxyallylsilanes
via a Chiral (Z)- -Silylallylboronate
â
γ
Ricardo Lira and William R. Roush*
Department of Chemistry, Scripps Florida, Jupiter, Florida 33458
roush@scripps.edu
Received August 2, 2007
ABSTRACT
syn-â
-Hydroxyallylsilanes of general structure 11 and 28 are prepared in 50
−86% yield and 91
−95% ee (for aliphatic aldehydes; 50% ee for
benzaldehyde) via the BF3
‚
Et2O-promoted -silylallylboration reactions, using reagents 14 and 15.
γ
The Lewis acid-promoted [3+2]-annulation reaction of chiral
allylsilanes and carbonyl electrophiles is an important method
for the synthesis of substituted tetrahydrofurans.1-7 Previous
studies in our laboratory have demonstrated that â-alkoxy-
allylsilanes 1 undergo highly diastereoselective [3+2]-
annulation reactions with aldehydes and certain highly
activated ketones, with the stereochemical outcome depend-
ing on the nature of the Lewis acid-carbonyl electrophile
combination (Figure 1). Under nonchelate controlled condi-
tions (BF3‚OEt2 catalysis), the 2,5-cis-tetrahydrofurans 4 are
obtained with g20:1 selectivity, whereas when a chelating
Lewis acid such as SnCl4 is employed (in concert with a
carbonyl electrophile that is capable of supporting a chelate
with the Lewis acid), the 2,5-trans-tetrahydrofurans 5 are
obtained, also with g20:1 selectivity.3 We have employed
this technology in the total syntheses of asimicin,8 bullaticin,9
and amphidinolide E,10-12 as well as in approaches to the
synthesis of pectenotoxin-2,13 amphidinolides C and F,14 and
angelmicin B.15
(1) Masse, C. E.; Panek, J. S. Chem. ReV. 1995, 95, 1293 and references
cited therein.
(2) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 3173.
(3) Micalizio, G. C.; Roush, W. R. Org. Lett. 2000, 2, 461.
(4) Peng, Z.-H.; Woerpel, K. A. Org. Lett. 2000, 2, 1379.
(5) Peng, Z.-H.; Woerpel, K. A. Org. Lett. 2002, 4, 2945.
(6) Peng, Z.-H.; Woerpel, K. A. J. Am. Chem. Soc. 2003, 125, 6018.
(7) Akiyama, T.; Funaki, S.; Fuchibe, K. Heterocycles 2006, 67, 369.
Figure 1. [3+2]-Annulation reactions of anti-â-alkoxyallylsilanes.
10.1021/ol7018746 CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/15/2007

anti-â-Alkoxyallylsilanes 1 are synthesized with 80-92%
ee via the asymmetric allylboration reactions of aldehydes
with chiral allylboronate 6 or allylboronate 7.16,17 However,
attempts to extend this methodology to the enantioselective
synthesis of the syn-â-alkoxyallylsilanes 11, needed for the
enantioselective synthesis of substituted tetrahydrofurans 12
and 13, have proven to be unexpectedly challenging. The
reactions of aldehydes with the tartrate ester modifed (Z)-
γ-silylallylboronate 8 proceed with only 50-60% ee,9 and
attempts to generate 9 via hydroboration of silylallene 10
with (Ipc)2BH at low temperature give the (E)-γ-silyl-
allylborane 7 with excellent selectivity, presumably via
thermodynamically controlled isomerization of the kinetically
formed (Z)-γ-silylallylborane.18,19
use of catalytic amounts of Lewis acid greatly enhances the
rates of reactions of allylboronates and aldehydes. Hall also
demonstrated that under Lewis acid-promoted reaction
conditions, crotylborations of aliphatic aldehydes using
reagents incorporating Hoffmann’s chiral auxiliary 1622
proceed with excellent enantioselectivity.23
(Z)-γ-Silylallylboronates 14 and 15 seemed ideally suited
for synthesis via Matteson’s R-halomethylboronate alkylation
chemistry.24,25 Thus, transesterification of the iodomethyl-
boronic ester 17 with diol 1622,26 provided the chiral
iodomethylboronic ester 18 (Figure 3). However, in spite of
Figure 2. (Z)-γ-Silylallylborating agents for the enantioselective
synthesis of syn-â-alkoxyallylsilanes 11.
Figure 3. Synthesis of (Z)-γ-silylallylborates 14, 15, and 26.
considerable experimentation, treatment of 18 with the
cyanocuprate 19a (which we previously employed in the
synthesis of 8)9 or with the (Z)-silylvinyllithium 21 (gener-
ated by treatment of vinylstannane 2027 with BuLi in THF
at -78 °C) did not provide the targeted silylallylboronates
14 or 15; only vinylsilane 22 resulting from protonation of
19a or 21 was obtained.
Successful syntheses of 14 and 15 were ultimately
achieved by addition of chloromethyllithium28 to vinylbor-
onates 24 and 25.29 The (Z)-silylvinylbororonates 24 and 25
were prepared in 69-71% yields by treatment of boronate
We report herein the synthesis and allylborations of the
chiral (Z)-γ-silylallylboronates 14 and 15, which undergo
Lewis acid accelerated reactions with aldehydes at -78 °C
and give the targeted syn-â-hydroxyallylsilanes 11a with
excellent enantioselectivity (typically >90% ee). This solu-
tion to the problem posed by the synthesis of 11a was
stimulated by recent reports by Ishiyama20 and Hall21 that
(8) Tinsley, J. M.; Roush, W. R. J. Am. Chem. Soc. 2005, 127, 10818.
(9) Tinsley, J. M.; Mertz, E.; Chong, P. Y.; Rarig, R.-A. F.; Roush, W.
R. Org. Lett. 2005, 7, 4245.
(10) Va, P.; Roush, W. R. J. Am. Chem. Soc. 2006, 128, 15960.
(11) Va, P.; Roush, W. R. Org. Lett. 2007, 9, 307.
(12) Va, P.; Roush, W. R. Tetrahedron 2007, 63, 5768.
(13) Micalizio, G. C.; Roush, W. R. Org. Lett. 2001, 3, 1949.
(14) Shotwell, J. B.; Roush, W. R. Org. Lett. 2004, 6, 3865.
(15) Lambert, W. T.; Roush, W. R. Org. Lett. 2005, 7, 5501.
(16) Roush, W. R.; Grover, P. T. Tetrahedron 1992, 48, 1981.
(17) Roush, W. R.; Pinchuk, A. N.; Micalizio, G. C. Tetrahedron Lett.
2000, 41, 9413.
(18) Roush, W. R.; Chong, P. Unpublished research.
(19) Narla, G.; Brown, H. C. Tetrahedron Lett. 1997, 38, 219.
(20) Ishiyama, T.; Ahiko, T.-a.; Miyaura, N. J. Am. Chem. Soc. 2002,
124, 12414.
(22) Herold, T.; Schrott, U.; Hoffman, R. W.; Schnelle, G.; Ladner, W.;
Steinbach, K. Chem. Ber. 1981, 114, 359.
(23) Lachance, H.; Lu, X.; Gravel, M.; Hall, D. G. J. Am. Chem. Soc.
2003, 125, 10160.
(24) Matteson, D. S. Chem. ReV. 1989, 89, 1535.
(25) Matteson, D. S. Tetrahedron 1998, 54, 10555.
(26) Diol 16 was synthesized by a four-step sequence recently developed
by Hall: Lachance, H.; St-Onge, M.; Hall, D. G. J. Org. Chem. 2005, 70,
4180.
(27) Marakami, M.; Matsuda, T.; Itami, K.; Ashida, S.; Terayama, M.
Synthesis 2004, 9, 1522.
(21) Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc. 2002, 124, 11586.
(28) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687.
4316
Org. Lett., Vol. 9, No. 21, 2007

23 with the vinyllithiums 21a or 21b (which were generated
by treatment of vinylstannanes 20a and 20b, respectively,
with n-BuLi in THF at -78 °C). Dropwise addition of 1.1
equiv of n-BuLi to a -78 °C mixture of 1.5 equiv of
chloroiodomethane and the corresponding vinyl boronate
ester (24 or 25) in THF provided the targeted (Z)-γ-
silylallylboronates 14 and 15 in 71-79% yield after chro-
matographic purification. Reagents 14 and 15 are stable to
chromatography and could be stored at -20 °C for long
periods of time without any apparent decomposition.30 An
analogous sequence was employed for the synthesis of the
related pinanediol-derived (Z)-γ-silylallylboronate 26.
and the syn-â-hydroxyallylsilane 11c was obtained in 85%
yield (entry 5). Also noteworthy is that 11c was obtained
with 95% ee as judged by Mosher esters analysis,34 and the
diastereomeric anti-â-hydroxyallylsilane was not detected
(g98:2 dr).
Results of the BF3‚OEt2-promoted allylborations of rep-
resentative aldehydes are summarized in Figure 4. The
Table 1. Optimization of Conditions for Allylboration
Reactions of 14
entry
reaction conditions
product(s) (%)a
no reactionb
1
2
3
4
5
Sc(OTf)3 (10 mol %), 32 h, -78 °C
Sc(OTf)3 (10 mol %), 48 h, -50 °C
BF3·OEt2 (100 mol %), 14 h, -78 °C 27 (63%)
BF3·OEt2 (100 mol %), 1 h, -78 °C
BF3·OEt2 (10 mol %), 3 h, -78 °C
no reactionb
27 (20%) + 11c (30%)
11c (85%)
a Yield of isolated product(s). b Based on 1H NMR analysis of the crude
reaction mixture.
Table 1 summarizes the definition of conditions for the
Lewis acid-promoted allylboration reactions of the (Z)-γ-
silylallylboronate 14. At the outset, we were concerned that
the product allylsilane 11c might be unstable with respect
to Lewis acid-promoted Peterson elimination under the
reaction conditions,31 or that 11c might react further with a
second equivalent of aldehyde to give dihydropyran prod-
ucts.32,33 While the latter pathway was not observed, the
Petersen elimination of 11c was a serious problem under
certain conditions, especially when BF3‚OEt2 was used to
promote the allylboration reaction (Table 1). No reaction was
observed when a mixture of 14 and hydrocinnamaldehyde
(1.1 equiv) were treated with 10 mol % of Sc(OTf)3 even
up to -50 °C for extended time periods (entries 1 and 2).
When the reaction was performed with stoichiometric BF3‚
OEt2 for 14 h, the only isolated product was diene 27 (63%
yield, entry 3). However, at shorter reaction times (entry 4),
and especially when 10 mol % of BF3‚OEt2 was used as
catalyst, the Petersen elimination pathway was suppressed
Figure 4. Enantio- and diastereosynthesis of syn-â-hydroxyallyl-
silanes via BF3‚OEt2a catalyzed allylboration of aldehydes with (Z)-
γ-silylallylboronates 14 and 15. Footnotes: (a) 10 mol % BF3‚
OEt2 was employed unless otherwise indicated; (b) determined by
Mosher esters analysis; (c) 15% of 14 was also recovered; (d) 20
mol % of BF3‚OEt2 was employed.
reactions with aliphatic aldehydes consistently provided the
syn-â-hydroxyallylsilane products 11c, 11d, 11e, 11f, and
11h with 91-95% ee (Mosher ester analysis).34 Similar
results were obtained in the synthesis of 28 (92% ee) from
the trimethylsilyl-substituted allylboronate 15. We previously
had been able to achieve only 50-64% ee for the γ-silyl-
allylboration of aldehydes by using reagent 8.9 The only
outlier from the trend of superior enantioselectivity for the
BF3‚OEt2-promoted allylborations with 14 (and 15) is the
allylboration of benzaldehyde, which provided 11g with only
50% ee. All attempts to improve this result by variation of
(29) While our work was in progress Hall reported the synthesis of a
type (III) bis-metal allyl reagent by a similar homologation process: Peng,
F.; Hall, D. G. J. Am. Chem. Soc. 2007, 129, 3070.
(30) 1H NMR analysis of samples of 14 and 15 stored at -20 °C for 8
weeks showed no signs of decomposition and/or olefin isomerization.
(31) Peterson, D. J. J. Org. Chem. 1968, 33, 780.
(32) Roush, W. R.; Dilley, G. J. Synlett 2001, 955.
(33) Huang, H.; Panek, J. S. J. Am. Chem. Soc. 2000, 122, 9836 and
references cited therein.
(34) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34,
2543.
Org. Lett., Vol. 9, No. 21, 2007
4317

reaction conditions were unsuccessful. Hall has also found
that aromatic aldehydes were poor substrates for the Lewis
acid-promoted crotylboration reaction.23
Surprisingly, however, attempts to use the pinanediol
derived reagent 26 in Lewis acid-promoted allylboration
reactions were completely unsuccessful, with no reaction
being observed under a variety of conditions (Figure 5).
Figure 6. Double asymmetric syn-γ-silylallylboration reactions of
14.
11 and 28 via the BF3‚OEt2-promoted γ-silylallylborations
of aliphatic aldehydes with reagents 14 and 15. Aliphatic
aldehydes undergo the γ-silylallylboration reaction with 91-
95% ee, whereas the selectivity with benzaldehyde is much
lower (50% ee). Utilization of this technology in several
ongoing synthesis projects will be reported in due course.
Figure 5. Attempted allylboration reactions with pinanediol derived
reagent 26. Footnote: (a) conditions employed in Table 1 failed to
provide any of the allylboration product as judged by H NMR
1
analysis of the crude reaction mixtures.
Finally, double asymmetric γ-silylallylboration reactions
of 29 and ent-29 with 14 are summarized in Figure 6. These
reactions were much slower than those summarized in Figure
4, and required 2 to 4 days with 30% BF3‚OEt2 at -55 °C.
That the diastereoselectivity of these two transformations was
only 6-7:1, and given the very long reaction times, suggests
that some racemization of 29 (or ent-29) may have occurred
under the reaction conditions, thereby limiting the overall
reaction diastereoselectivity.
Acknowledgment. This work was supported by the
National Institutes of Health (GM 38436).
Supporting Information Available: Experimental pro-
cedures and tabulated spectroscopic data for all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
In summary, we have developed a convenient method for
synthesis of syn-â-hydroxyallylsilanes of general structure
OL7018746
4318
Org. Lett., Vol. 9, No. 21, 2007