ISSN:
0009-2940
Keywords:
tert-Leucine
;
Diazotation
;
Butanoic acid, (S)-2-chloro-3,3-dimethyl-, and derivatives
;
Aziridinones
;
α-Lactams
;
Amino acids, α-alkyl-, and esters
;
Oxazolidine-2,5-diones
;
Circular dichroism
;
Chemistry
;
Inorganic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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 tBuOK, 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 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 [(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=tBu) which is the crucial intermediate formed in the diazotization of (S)-14.
Additional Material:
7 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/cber.19911240427
