23985-53-7Relevant articles and documents
Synthesis of a Chiral, Nonracemic Aziridinone (α-Lactam)
Quast, Helmut,Leybach, Holger
, p. 849 - 859 (2007/10/02)
(S)-tert-Leucine 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 51percent yield of pure (S)-15 (e.e. >= 97.4percent) which is converted via the acid chloride (S)-17 into the α-chloro amides (S)-18a and b (e.e. = 99.0 and 95.2percent, respectively).On treatment with tBuOK, the latter is converted into the α-lactam (R)-22b (59percent, e.e. >= 91.0percent, D20 = -293.7), which is accompanied by small amounts of its ring opening product (R)-23b.Only the α-amino ester (R)-23a is formed from the α-chloro amide (S)-18a and tBuOK.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 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 = tBu) which is the crucial intermediate formed in the diazotization of (S)-14.
