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Silylcyanation of Aldehydes, Ketones, and Imines Catalyzed by a 6,6′‐Bis‐sulfonamide Derivative of 7,7′‐Dihydroxy‐8,8′‐biquinolyl (azaBINOL)
Author(s) -
Sephton Selena Milicevic,
Wang Chao,
Zakharov Lev N.,
Blakemore Paul R.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200333
Subject(s) - chemistry , strecker amino acid synthesis , trimethylsilyl cyanide , benzaldehyde , aryl , sulfonamide , intramolecular force , alkyl , medicinal chemistry , cyanohydrin , catalysis , hydrogen bond , toluene , organic chemistry , stereochemistry , enantioselective synthesis , molecule
6,6′‐Bis(methylaminosulfonyl)‐7,7′‐dihydroxy‐8,8′‐biquinolyl ( 3 ) catalyzes (5–10 mol‐%) the addition of trimethylsilyl cyanide to aldehydes (aryl, alkyl, and α,β‐unsaturated; 42–92 % yields), ketones (aryl alkyl, dialkyl; 22–82 % yields), and N ‐benzylaldimines (14–78 % yields) in toluene (0 °C or room temp.) to give the expected cyanohydrin and Strecker adducts following desilylation. Among a series of closely related compounds lacking any one of their defining structural features, bis‐sulfonamide 3 and its N , N′ ‐dimethyl derivative are exceptional in catalyzing the silylcyanation of benzaldehyde in the absence of all other additives. Hammett analysis of the competitive silylcyanation of para ‐substituted benzaldehydes catalyzed by 3 showed a linear free‐energy relationship ( R 2 = 0.928) with a modest positive reaction constant ( ρ = +1.52). X‐ray diffraction analysis of (±)‐ 3 indicated a cisoid biaryl conformation and the existence of an intramolecular hydrogen bond between C7′–OH and C7–O. Resolution of (±)‐ 3 was achieved by HPLC separation of its tetravalerate derivative on a chiral stationary phase. The absolute configurations of the optical isomers of 3 were assigned by correlation of the ECD spectra with those of related biquinolyls of known configuration. The silylcyanation of aldehydes catalyzed by (–)‐( aR )‐ 3 leads to cyanohydrins with a preference for the ( S )‐configured product with an ee of <10 %. The organocatalytic action of 3 is ascribed to hydrogen bonding and Brønsted acid catalysis effects that are dependent on its acidifying sulfonamide groups, general base capability, and interannular proximity effects made possible by the biaryl structure.