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Scope and limitations of the TiCl 4 ‐mediated additions of isocyanides to aldehydes and ketones with formation of α‐hydroxycarboxylic acid amides
Author(s) -
Seebach Dieter,
Adam Geo,
Gees Thomas,
Schiess Martin,
Weigand Wolfgang
Publication year - 1988
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19881210319
Subject(s) - chemistry , ketone , medicinal chemistry , cyclohexanone , isocyanide , acetophenone , aldehyde , stereochemistry , organic chemistry , catalysis
The adducts obtained from TiCl 4 and achiral ( 8 – 12 ) or chiral, nonracemic ( 13 – 22 ) isocyanides are combined with aldehydes (aromatic or aliphatic) and ketones (acetone, cyclohexanone, acetophenone) to give, after aqueous workup, α‐hydroxyamides ( 27 – 55 ) [Passerini‐type reaction]. The transformation is compatible with a variety of functional groups (aromatic and heterocyclic rings, amino, ether, ester, and amido groups, halides, and phosphonate substituents). The yields range from 14 to over 95% (with the lower values in the case of more highly functionalised isocyanides). No diastereoselectivity is observed with chiral isocyanides. If the R groups of the isocyanide (RNC) form a rather stable cation ( t ‐alkyl or benzylic), cyanohydrins may result from the reaction, rather than the N ‐substituted α‐hydroxyamides (see Scheme 2).