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Acylation of Alkyl Halides and Amino Aldehydes with a Phosphane Oxide‐Based d 1 ‐Synthon
Author(s) -
Brünjes Marco,
Kujat Christof,
Monenschein Holger,
Kirschning Andreas
Publication year - 2004
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.200300631
Subject(s) - chemistry , sharpless asymmetric dihydroxylation , amino acid , alkyl , protonation , synthon , yield (engineering) , organic chemistry , medicinal chemistry , adduct , methyl group , acylation , oxide , stereoselectivity , catalysis , ion , biochemistry , materials science , metallurgy
Alkyl iodides and α‐amino aldehydes can be homologated to the corresponding methyl esters and β‐amino methyl esters, including β‐amino‐α‐hydroxy methyl esters, using lithiated (dimethoxymethyl)diphenylphosphane oxide. The primary α,α‐(dimethoxy)diphenylphosphane oxides obtained by this Horner−Wittig type process collapse to give the target esters under proton‐catalyzed conditions in the presence of water. Detailed and carefully conducted mechanistic studies revealed that the diphenylphosphane oxide group is activated by protonation, and acts as the initial leaving group in this process. In the cases of adducts derived from the reaction of the phosphane oxide‐stabilized anion with α‐amino aldehydes, homologation to the β‐amino‐ and β‐amino‐α‐hydroxy methyl esters can be achieved by KO t Bu‐mediated elimination to the intermediate O , O ‐ketene acetals. These may either be allowed to react with water under acidic conditions to yield the β‐amino methyl esters, or may be treated under the Sharpless asymmetric dihydroxylation conditions to directly furnish the β‐amino‐α‐hydroxy methyl esters. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)