Highly diastereoselective preparation of (E)-alkenylsilanes bearing an α-chiral center

Article abstract of DOI:10.1021/ol063097o

(Chemical Equation Presented) The copper(I)-mediated anti-S _N2′ allylic substitution allows a highly stereoselective preparation of alkenylsilanes bearing a chiral center in the α-position with high transfer of chirality. These alkenylsilanes were converted into α,β-unsaturated ketones or into the corresponding boronic esters without loss of the chiral information.

Full text of DOI:10.1021/ol063097o

ORGANIC
LETTERS
2007
Vol. 9, No. 6
1041-1044
Highly Diastereoselective Preparation of
(E)-Alkenylsilanes Bearing an
Center
r-Chiral
Sylvie Perrone and Paul Knochel*
Department Chemie und Biochemie, Ludwig-Maximilians-UniVersita¨t,
Butenandtstrasse 5-13, D-81377 Mu¨nchen, Germany
paul.knochel@cup.uni-muenchen.de
Received December 21, 2006
ABSTRACT
The copper(I)-mediated anti-SN2
′
allylic substitution allows a highly stereoselective preparation of alkenylsilanes bearing a chiral center in the
-unsaturated ketones or into the corresponding boronic
r
-position with high transfer of chirality. These alkenylsilanes were converted into
r,â
esters without loss of the chiral information.
Organosilicon chemistry1 has a broad impact on organic
methodology and total synthesis. Alkenylsilanes have been
particularly used in palladium-catalyzed cross-coupling reac-
tions since the pioneering work of Hiyama.2 In recent years,
this reaction has been increasingly investigated.3,4 The
preparation of alkenylsilanes remains a challenging task, and
there have been only a few reports of alkenylsilanes con-
taining an adjacent carbon stereogenic center.
We have recently reported an efficient anti-SN2′ allylic
substitution5,6 with almost complete transfer of the chiral
information.7 This method can be applied to the asymmetric
synthesis of tertiary alcohols or amines8 and for the prepara-
tion of ketones bearing an R-chiral center.9 Herein, we report
the diastereoselective preparation of (E)-alkenylsilanes con-
taining an R-stereogenic center of type 1 via anti-SN2′ allylic
(1) (a) Colvin, E. Silicon in Organic Synthesis; Butterworth: New York,
1981. (b) Weber, W. P. Silicon Reagents for Organic Synthesis. In ReactiVity
and Structure Concepts in Organic Chemistry 14; Springer-Verlag: Berlin,
Heidelberg, 1983. (c) Brook, M. A. Silicon in Organic, Organometallic
and Polymer Chemistry; Wiley: New York, 2000.
(2) (a) Hiyama, T. Metal Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter 10. (b)
Hiyama, T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61. (c) Hatanaka,
Y.; Hiyama, T. Synlett 1991, 845.
(3) For reviews, see for example: (a) Denmark, S. E.; Sweis, R. F. Chem.
Pharm. Bull. 2002, 50, 1531. (b) Denmark, S. E.; Sweis, R. F. Acc. Chem.
Res. 2002, 35, 835.
(4) (a) Trost, B. M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5,
1895. (b) Anderson, J. C.; Anguille, S.: Bailey, R. Chem. Commun. 2002,
2018. See also the work of Yoshida: (c) Itami, K.; Mitsudo, K.; Kamei,
T.; Koike, T.; Nokami, T.; Yoshida, J. J. Am. Chem. Soc. 2000, 122, 12013.
(d) Itami, K.; Nokami, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 5600.
(e) Itami, K.; Nokami, T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida,
J. J. Am. Chem. Soc. 2001, 123, 11577.
(5) (a) Demel, P.; Keller, M.; Breit, B. Chem. Eur. J. 2006, 12, 6669;
6684. (b) Breit, B.; Demel, P. AdV. Synth. Catal. 2001, 343, 429. (c) Breit,
B.; Demel, P. Tetrahedron 2000, 56, 2833. (d) Breit, B. Chem. Eur. J.
2000, 6, 1519. (e) Breit, B.; Demel, P.; Studte, C. Angew. Chem., Int. Ed.
2004, 43, 3785. (f) Herber, C.; Breit, B. Angew. Chem., Int. Ed. 2005, 44,
5267. (g) Breit, B.; Herber, C. Angew. Chem., Int. Ed. 2004, 43, 3790. (h)
Breit, B. Angew. Chem., Int. Ed. 1998, 37, 525. (i) Smitrovich, J. H.;
Woerpel, K. A. J. Org. Chem. 2000, 65, 1601. (j) Spino, C.; Beaulieu, C.;
Lafreniere, J. J. Org. Chem. 2002, 65, 7091. (k) Belelie, J. L.; Chong, J.
M. J. Org. Chem. 2001, 66, 5552. (l) Ibuka, T.; Habashita, H.; Otaka, A.;
Fujii, N.; Oguchi, Y.; Uyehara, T.; Yamamoto, Y. J. Org. Chem. 1991, 56,
4370. (m) Yamamoto, Y.; Tanaka, M.; Ibuka, T.; Chounan, Y. J. Org. Chem.
1992, 57, 1024. (n) Marino, J. P.; Viso, A.; Lee, J.-D.; Fernandez de la
Pradilla, R.; Fernandez, P.; Rubio, M. B. J. Org. Chem. 1997, 62, 645.
10.1021/ol063097o CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/17/2007

substitution reactions with diorganozinc reagents mediated
by Cu(I) salt.
Table 1. Preparation of (E)-Alkenylsilanes of Type 1 by
Copper(I)-Mediated anti-SN2′ Substitution of Allylic Silanes 2
As the substituents at silicon may influence the reactivity
of the resulting alkenylsilanes,3 two different allylic substrates
were prepared: 2a (t-BuMe2Si residue) and 2b (PhMe2Si
residue). These allylic silanes undergo highly stereoselective
SN2′ substitutions as shown in Scheme 1. The allylic silane
Scheme 1. Diastereoselective anti-SN2′ Allylic Substitution on
Allylic Silanes of Type 2
2a was prepared starting from the R-hydroxysilane 3a, which
was obtained via a retro-Brook rearrangement reaction
starting from 2-butyn-1-ol10 (Scheme 2). Subsequent Jones
Scheme 2. Synthesis of (R,Z)-Allylic Pentafluorobenzoyl
Silanes 2a and 2b
oxidation gave the silyl ketone 4a (90%) whose enantiose-
lective reduction with BH3‚Me2S in the presence of (R)-2-
methyl-CBS-oxazaborolidine11 led to the alcohol (+)-(R)-
3a in 92% yield and 92% ee.12 The (Z)-hydroxyalkenylsilane
(R)-5a was obtained by selective hydrogenation using a
Lindlar catalyst10 (>95% Z isomer, 80%). Finally, the
reaction with pentafluorobenzoyl chloride in the presence
of pyridine and a catalytic amount of DMAP gave the
pentafluorobenzoyl allylic silane (R,Z)-2a in 95% yield. The
allylic silanes (R,Z)-2b was prepared in a similar way in 90%
ee (Scheme 2).
In a typical procedure, (Z)-pentafluorobenzoate 2a (92%
ee, entry 1 of Table 1) was treated with Pent2Zn (2.4 equiv)
in the presence of CuCN‚2LiCl (1.2 equiv) in a mixture of
THF and NMP (2:1), and after 24 h at -50 °C afforded the
expected anti-SN2′ substituted product 1a (81%, 90% ee) with
excellent transfer of chirality. A secondary diorganozinc such
as i-Pr2Zn (entry 2) reacts also with high SN2′ regioselectivity
(no SN2 product observed). The corresponding alkenylsilane
1b was obtained in 90% yield and 90% ee. Et2Zn led to the
a The enantiomeric excess was determined by HPLC or GC analysis on
product 1, 2, or derivatives. In each case the racemic product was used for
calibration. b Isolated yield of analytically pure product.
expected product 1c (89%, 88% ee, entry 3). The substitution
not only was limited to alkylzinc reagents but also proceeded
well with diarylzincs. Thus, Ph2Zn reacted smoothly with
3a in the presence of CuCN‚2LiCl to afford 1d (86%, 89%
ee, entry 4). More interestingly, functionalized diarylzinc
reagents13 reacted similarly, providing the corresponding
methyl benzoate derivative 1e (65%, 89% ee, entry 5) and
o-methoxy benzene derivative 1f (60%, 90% ee, entry 6).
A zinc reagent such as [Ph(CH2)2]2Zn led to moderate
results as a result of its lower reactivity and therefore higher
required temperature (-30 °C to room temperature, 24 h,
60%, 84% ee, entry 7). Modification of the substituents on
the silicon atom did not affect the level of the transfer of
1042
Org. Lett., Vol. 9, No. 6, 2007

chirality. Thus, Me2Zn (2.4 equiv) reacted smoothly with
(Z)-pentafluorobenzoate 2b (entry 8) in the presence of
CuCN‚2LiCl (1.2 equiv) at -30 °C for 16 h and afforded
the expected substituted product 1h with almost no loss of
the enantiomeric excess (89% ee) and in 95% yield. Et2Zn
(entry 9, 86%, 89% ee), i-Pr2Zn (entry 10, 89%, 87% ee),
and Ph2Zn (entry 11, 93%, 89% ee) gave excellent results,
although the addition of i-Pr2Zn showed a poorer transfer
(87% ee recovered) probably due to steric hindrance.
Table 2. Preparation of (E)-R,â-Unsaturated Ketone 6 by
Stereoselective Friedel-Crafts Acylation on Alkenylsilanes 1
Alkenylsilanes of type 1 underwent Friedel-Crafts acy-
lation-type reactions,14 providing a synthesis of R,â-unsatur-
ated ketones of type 6 (Scheme 3). Thus, the alkenylsilane
Scheme 3. Stereoselective Friedel-Crafts Acylation of
Alkenylsilanes of Type 1
1a (entry 1 of Table 2) was treated with AlCl3 (1.1 equiv)
and benzoyl chloride (1.1 equiv) in CH2Cl2 (-78 °C, 3 h,
25 °C) and afforded the corresponding (E)-R,â-unsaturated
(6) For copper-catalyzed reactions using chiral ligands, see: (a) van
Klaveren, M.; Persson, E. S. M.; del Villar, A.; Grove, D. M.; Ba¨ckvall,
J.-E.; van Koten, G. Tetrahedron Lett. 1995, 36, 3059. (b) Karlstro¨m, A.
S. E.; Huerta, F. F.; Meuzelaar, G. J.; Ba¨ckvall, J.-E. Synlett 2001, 923. (c)
Meuzelaar, G. J.; Karlstro¨m, A. S. E.; van Klaveren, M.; Persson, E. S.
M.; del Villar, A.; van Koten, G.; Ba¨ckvall, J.-E. Tetrahedron 2000, 56,
2895. (d) Du¨bner, F.; Knochel, P. Angew. Chem., Int. Ed. 1999, 38, 379.
(e) Du¨bner, F.; Knochel, P. Tetrahedron Lett. 2000, 41, 9233. (f) Alexakis,
A.; Malan, C.; Lea, L.; Benhaim, C.; Fournioux, X. Synlett 2001, 927. (g)
Alexakis, A.; Croset, K. Org. Lett. 2002, 4, 4147. (h) Tissot-Croset, K.;
Polet, D.; Alexakis, A. Angew. Chem., Int. Ed. 2004, 43, 2426. (i) Tissot-
Croset, K.; Alexakis, A. Tetrahedron Lett. 2004, 45, 7375. (j) Falciola, C.;
Tissot-Croset, K.; Alexakis, A. Angew. Chem., Int. Ed. 2006, 45, 5995. (k)
Alexakis, A.; Tomassini, A.; Andrey, O.; Bernardinelli, G. Eur. J. Org.
Chem. 2005, 1332. (l) Polet, D.; Alexakis, A. Org. Lett. 2005, 7, 1621. (m)
Malda, H.; Van Zijl, A. W.; Arnold, L. A.; Feringa, B. L. Org. Lett. 2001,
3, 1169. (n) Van Zijl, A. W.; Arnold, L. A.; Minnaard, A. J.; Feringa, B.
L. AdV. Synth. Catal. 2004, 346, 413. (o) Lo´pez, F.; Van Zijl, A. W.
Minnaard, A. J.; Feringa, B. L. Chem. Commun. 2006, 409. (p) Luchaco-
Cullis, C. A.; Mizutani, H.; Murphy, K. E.; Hoveyda, A. H. Angew. Chem.,
Int. Ed. 2001, 40, 1456. (q) Murphy, K. E.; Hoveyda, A. H. J. Am. Chem.
Soc. 2003, 125, 4690. (r) Kacprzynski, M. A.; Hoveyda, A. H. J. Am. Chem.
Soc. 2004, 126, 10676. (s) Larsen, A. O.; Leu, W.; Nieto Oberhuber, C.;
Campbell, J. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130. (t)
Van Veldhuisen, J. J.; Campbell, J. E.; Giudici; R. E.; Hoveyda, A. H. J.
Am. Chem. Soc. 2005, 127, 6877. (u) Lee, Y.; Hoveyda, A. H. J. Am. Chem.
Soc. 2006, 128, 15604. (v) Ongeri, S.; Piarulli, U.; Roux, M.; Monti, C;
Gennari, C. HelV. Chim. Acta 2002, 85, 3388.
a The enantiomeric excess was determined by HPLC or GC analysis. In
each case the racemic product was used for calibration. b Isolated yield of
analytically pure product.
ketone 6a with full retention of the chiral information (65%,
90% ee). Various acid chlorides could be similarly reacted.
For example, aliphatic acid chlorides such as the bulky
pivaloyl chloride (entry 2) or acetyl chloride (entry 3) were
added with retention of the (E)-stereochemistry (90% ee,
respectively, for 6b and 6c).
(7) (a) Harrington-Frost, N.; Leuser, H.; Calaza, M. I.; Kneisel, F. F.;
Knochel, P. Org. Lett. 2003, 5, 2111. (b) Soorukram, D.; Knochel, P. Org.
Lett. 2004, 6, 2409. (c) Calaza, M. I.; Hupe, E.; Knochel, P. Org. Lett.
2003, 5, 1059.
(8) Leuser, H.; Perrone, S.; Liron, F.; Kneisel, F. F.; Knochel, P. Angew.
Chem., Int. Ed. 2005, 44, 4627.
Interestingly substituted R,â-unsaturated furyl ketone 6d
(entry 4) could be easily prepared with high enantioselectivity
(9) Soorukram, D.; Knochel, P. Angew. Chem., Int. Ed. 2006, 45, 3686.
(10) Sakaguchi, K.; Higashino, M.; Ohfune, Y. Tetrahedron 2003, 59,
6647.
(11) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987,
109, 5551. (b) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37,
1986.
(13) (a) Kneisel, F. F.; Dochnahl, M.; Knochel, P. Angew. Chem., Int.
Ed. 2004, 43, 1017. (b) Kneisel, F. F.; Leuser, H.; Knochel, P. Synthesis
2005, 2625.
(14) (a) Paquette, L. A.; Fristad, W. E.; Dime, D. S.; Bailey, T. R. J.
Org. Chem. 1980, 45, 3017. (b) Zhao, H.; Cai, M.-Z. Synth. Commun. 2003,
33, 1643.
(12) Guintchin, B. K.; Bienz, S. Organometallics 2004, 23, 4944.
Org. Lett., Vol. 9, No. 6, 2007
1043

(66% yield, 90% ee) by this method. Similarly, alkenylsilanes
1i-k furnished the corresponding R,â-unsaturated ketones
6g (80%, 89% ee, entry 7), 6h (86%, 87% ee, entry 8), and
6i (75%, 89% ee, entry 9) when treated with AlCl3 and
benzoyl chloride with full retention of the stereochemical
information. Interestingly the fluoro-substituted R,â-unsatur-
ated ketone 6j (entry 10) was prepared in high enantiose-
lectivity by this method (68% yield, 89% ee).
Furthermore, chiral alkenylsilanes of type 1 could be suc-
cessfully borodesilylated.15 Thus, the treatment of alkenyl-
silane 1h with BCl3 (5 h at -30 °C) in CH2Cl2 followed by
derivatization with pinacol in the presence of triethylamine
(one pot) afforded the alkenyl boronopinacolate 7 in 72%
yield and 89% ee (Scheme 4).
ee with retention of the stereochemistry (Scheme 4).16 The
cross-coupling occurs under similar conditions when reacted
with PhI and gave the phenyl-substituted alkene 9 in 83%
yield and 89% ee.
In addition, an in situ ipso-borodesilylation-cross-coupling
procedure15 was performed in a one-pot operation. Thus, in
the presence of BCl3 (5 h, -30 °C), the alkenylsilane 7 was
converted into the intermediate dichloroborane 10, which
reacted in the typical Suzuki-Miyaura conditions with PhI
and Pd(PPh3)4 (5 mol %) to afford the expected disubstituted
alkene 9 in 60% yield and 89% ee (Scheme 5).
Scheme 5. Sequential ipso-Borodesilylation Followed by in
Situ Suzuki-Miyaura Cross-Coupling under Pd-Catalyzed
Conditions
Scheme 4. ipso-Borodesilylation of 1h and Successive
Suzuki-Miyaura Cross-Coupling
In summary, we have developed a highly diastereoselective
method for the preparation of (E)-alkenylsilanes bearing an
R-chiral center. These compounds are versatile intermediates
and could be readily converted into R,â-unsaturated ketones
by a Friedel-Crafts-type acylation or into the corresponding
alkenylboronates by an ipso-borodesilylation and then un-
dergo cross-coupling reactions. Further applications are
currently underway in our laboratories.
Acknowledgment. S.P. thanks the DFG for a fellowship.
The authors thank the Fonds der Chemischer Industrie,
Chemetall GmbH (Frankfurt), Degussa AG (Frankfurt), and
BASF AG (Ludwigshafen) for the generous gift of chemicals.
The boronate 7 was first reacted with p-ethyl iodobenzoate
in the presence Pd(PPh3)4 (5 mol %, 3 h at reflux in dioxane)
to give the aryl-substituted alkene 8 in 85% yield and 89%
Supporting Information Available: Experimental pro-
cedures and full characterization of all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(15) (a) Babudri, F.; Farinola, G. M.; Fiandanese, V.; Mazzone, L.; Naso,
F. Tetrahedron 1998, 54, 1085. (b) Itami, K.; Kamei, T.; Yoshida, J. J.
Am. Chem. Soc. 2003, 125, 14670. (c) Zhao, Z.; Snieckus, V. Org. Lett.
2005, 7, 2523.
OL063097O
(16) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
1044
Org. Lett., Vol. 9, No. 6, 2007