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Lewis Acid‐Mediated Acetal Substitution Reactions: Mechanism and Application to Asymmetric Catalysis
Author(s) -
Kobayashi Shū,
Arai Kenzo,
Yamakawa Takeshi,
Chen YiJing,
Salter Matthew M.,
Yamashita Yasuhiro
Publication year - 2011
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201100346
Subject(s) - chemistry , aldol reaction , oxocarbenium , enol , acetal , silylation , lewis acids and bases , adduct , silyl enol ether , enol ether , catalysis , enantioselective synthesis , substitution reaction , isomerization , medicinal chemistry , ketene , organic chemistry , nucleophile
Substitution reactions of acetals with carbon nucleophiles are fundamental and conventional organic reactions. We succeeded in the preparation of an optically active acetal, which reacted with a silyl enol ether smoothly to afford the desired adducts in racemic forms. By comparison of the ee s of the products with the ee s of the recovered acetals, we concluded that the aldol‐type reactions proceeded not via direct displacement (S N 2) or contact ion pairs (intimate ion pair) (S N 1) but by a free oxocarbenium ion (S N 1) mechanism. Next, a study to achieve asymmetric catalysis of the acetal substitution reactions was conducted. After many trials, it was found that a chiral niobium complex prepared from pentamethoxyniobium [Nb(OMe) 5 ] and a tetradentate BINOL derivative could achieve high enantioselectivities. Asymmetric aldol‐type reactions of acetals with silyl enol ethers proceeded smoothly to afford the corresponding aldol‐type adducts in good yields with high enantioselectivities.