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Reactions of Chiral 2‐( tert ‐Butyl)‐2 H ,4 H ‐1,3‐dioxin‐4‐ones Bearing Functional Groups in the 6‐Position and Diastereoselective Catalytic Hydrogenation to cis ‐2,6‐Disubstituted 1,3‐Dioxan‐4‐ones
Author(s) -
Noda Yoshihiro,
Seebach Dieter
Publication year - 1987
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19870700819
Subject(s) - chemistry , stereocenter , stereochemistry , double bond , alkylation , catalytic hydrogenation , catalysis , medicinal chemistry , hydrolysis , enantioselective synthesis , organic chemistry
( R )‐5‐Bromo‐6‐(bromomethyl)‐2‐( tert ‐butyl)‐2 H ,4 H ‐1,3‐dioxin‐4‐one ( 2 ) derived from ( R )‐3‐hydroxybutanoic acid is used for substitutions and chain elongations at the side‐chain C‐atom in the 6‐position of the heterocycle (→ 3–6 , 10–13 ). Subsequent simultaneous reductive debromination and double‐bond hydrogenation (Pd/C,H 2 )occurs with essentially complete diastereoselectivity (>98% ds), with H transfer from the face opposite to the t ‐Bu group (→ 15–20 , Table 1 ). Hydrolytic cleavages of the dioxanones then lead to enantiomerically pure β‐hydroxy‐acid derivatives (overall self‐reproduction of the stereogenic center of 3‐hydroxybutanoic acid or alkylation in the 4‐position of this acid with preservation of configuration).