Chapter 7
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Enantioselective Alkynylation of Aldehydes Catalyzed by New Chiral Catalysts Albert S. C. Chan, Gui Lu, and Xingshu Li Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
A series of amino alcohol ligands of binaphthyl derivatives were synthesized and were found to be effective in the enantioselective alkynylation of aldehydes. A variety of aromatic aldehydes were converted to the corresponding chiral propargylic alcohols in up to 93% e.e. Chiral catalyst systems by virtue of the cooperation of several chiral ligands were also developed. The alkynylation reaction proceeded smoothly to produce the desired products in up to 99.7% e.e.
© 2004 American Chemical Society
In Methodologies in Asymmetric Catalysis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.
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104
Chiral propargylic alcohols aie versatile building blocks in the synthesis of a broad variety of biologically active and structurally interesting compounds (1-3). Two general approaches to prepare optically active propargylic alcohols have been reported startingfromeither ynones or aldehydes.
Downloaded by PENNSYLVANIA STATE UNIV on July 21, 2013 | http://pubs.acs.org Publication Date: July 4, 2004 | doi: 10.1021/bk-2004-0880.ch007
Ο
aldehyde
Although direct reductions of α,β-ynones via chirally modified metal hydrides (4-8% reductive cleavage of chiral acetylenic acetals (0), enzymatic transformations (10-15), hydroboration with chiral oxazaborolidines (16-18), and transfer hydrogénation (19) are catalytic and quite effective, the method of alkynylation of aldehyde has a strategic synthetic advantage because the latter forms a new C-C bond with concomitant creation of a stereogenic center in a single transformation, while in the former the C-C bond and the stereogenic center are formed separately. Unlike the catalytic enantioselective addition of dialkyl- and alkenylzinc compounds to aldehydes where considerable progress has been made (20-23\ the current methods for enantioselective alkynylation reactions are still less developed due to either the use of stoichiometric amounts of catalysts, restricted substrates or the formation of considerable amounts of alkylated products (2445). Yamamoto et al(26) found that the reaction of a steroidal aldehyde 1 with stannylacetylene 2c in the presence of TiCl produced the Cram isomer 3 with high diastereoselectivity (at least 85:15). High selectivity also occured in the reaction of 1 with allylstannane and allylsilane. Krause and Seebach (27) prepared R-s-Ti(OiPr) and used it in the alkynylation of aldehydes with only low to moderate diastereoselectivity. Soai et al.(28,29) reported the syntheses of alkynyl alcohols by the enantioselective addition of alkynylzinc reagents to aldehydes in the presence of catalytic amounts of amino alcohols and found that (15,2i?)-(-)dibutylnorephedrine (5, DBNE) gave moderate e.e., while (5)-(+)-(lmethylpyrrolidin-2-yl)diphenylmethanol (6, MPDPM) afforded 78% e.e. 4
3
In Methodologies in Asymmetric Catalysis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.
Downloaded by PENNSYLVANIA STATE UNIV on July 21, 2013 | http://pubs.acs.org Publication Date: July 4, 2004 | doi: 10.1021/bk-2004-0880.ch007
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Ar
X
ZnMe , toluene 2
Η *
H-^-K
HO^^H
ΑΓ\
2
llgand, 10mol%
^\ R
2
Η
