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Synthese eines chiralen, nicht‐racemischen Aziridinons (α‐Lactams) 1,2)
Author(s) -
Quast Helmut,
Leybach Holger
Publication year - 1991
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.19911240427
Subject(s) - chemistry , racemization , amide , enantiomer , stereocenter , lactam , hydrolysis , stereochemistry , yield (engineering) , enantiomeric excess , medicinal chemistry , enantioselective synthesis , organic chemistry , catalysis , materials science , metallurgy
Synthesis of a Chiral, Nonracemic Aziridinone (α‐Lactam) 1,2 ) (S)‐ tert ‐Leucine [(S)‐ 14 ] is diazotized affording a mixture of the expected α‐chloro and α‐hydroxy acids (S)‐ 15 and (S)‐ 16 and the rearranged β‐chloro and β‐hydroxy acids (R)‐ 12 and (S)‐ 11 . Separation produces a 51% yield of pure (S)‐ 15 (e.e. ° 97.4%) which is converted via the acid chloride (S)‐ 17 into the α‐chloro amides (S)‐ 18a and b (e.e.=99.0 and 95.2%, respectively). On treatment with t BuOK, the latter is converted into the α‐lactam (R)‐ 22b (59%, e.e. ° 91.0%, [α°=−293.7), which is accompanied by small amounts of its ring‐opening product (R)‐ 23b . Only the α‐amino ester (R)‐ 23 a is formed from the α‐chloro amide (S)‐ 18a and t BuOK. While the enantiomers of the halo amides 13, 18a, b, 24a, b and of the 3‐pentyl esters of the hydroxy acid 16 are separated by GC on chiral columns, the α‐lactam 22b and the α‐amino esters 23a, b require conversion into separable derivatives without involving the stereogenic center. Thus, alkaline hydrolysis of 22b as well as acidic cleavage of 23 yield the α‐amino acids 25 which are cyclized to the oxazolidine‐2,5‐diones 26 by means of bis(trichloromethyl) carbonate (“triphosgene”). As shown by the high enantiomeric excess of the products derived from (S)‐ tert ‐leucine [(S)‐ 14 ] none of the reactions described results in a considerable degree of racemization. Authentic samples of 11 and 12 are synthesized from the Reformatzky product 21 . The absolute configurations of the major enantiomers derived from (S)‐ 14 are based on the retention on chiral GC columns, the signs of optical rotations, and CD spectra. The mechanism of the rearrangement leading to the β‐hydroxy and β‐chloro acids (S)‐ 11 and (R)‐ 12 is interpreted in terms of a stereospecific 1,2‐methyl shift occurring simultaneously with the ring cleavage of the (protonated) α‐lactone (R)‐ 2 (R= t Bu) which is the crucial intermediate formed in the diazotization of (S)‐ 14 .