A New Chiral Auxiliary Derived from (2S)-Phenylglycinol: an Access to Enantiomerically Pure β-Amino Acids

Abstract

A new bicyclic heterocycle 3, which is potentially useful for the synthesis of b-amino acids, has been obtained from a reaction between (S)-phenylglycinol and cyanogen bromide followed by a condensation with methyl propiolate. Conjugate additions of different organocuprate reagents to this chiral Michael acceptor occurred with complete diastereoselectivity. An optically pure b amino acid was obtained in excellent yield from the masked chiral derivative 4a.

Modified multicomponent Biginelli–Atwal reaction towards a straightforward construction of 5,6-dihydropyrimidin-4-ones

“…Accordingly, we intended to capitalize on the readily availability of 12 (one-step from (R)-2-phenylglycinol) which was developed as useful chiral auxiliary by Dechoux and colleagues. 18,19 Following our optimized conditions (entry 1), using an equivalent of Na 2 CO 3 and benzaldehyde 5a, the MCR proceeded smoothly but furnished a 1 : 1 mixture of regioisomers 13a and 14a versus 15a and 16a from which the known anti-dihydropyrimidin-4-one 13a was the major diastereomer. 18 We were delighted to see that base-free conditions, making use of enolate 4 À Na + and ammonium salt 11, not only favored regioisomers 13a and 14a (13a,14a/15a,16a ¼ 66/34) but 3-pyridine (5e) 3 4 ( 7ae) revealed a good diastereoisomeric ratio of 92 : 8 (13a : 14a, entry 2).…”

“…18,19 Following our optimized conditions (entry 1), using an equivalent of Na 2 CO 3 and benzaldehyde 5a, the MCR proceeded smoothly but furnished a 1 : 1 mixture of regioisomers 13a and 14a versus 15a and 16a from which the known anti-dihydropyrimidin-4-one 13a was the major diastereomer. 18 We were delighted to see that base-free conditions, making use of enolate 4 À Na + and ammonium salt 11, not only favored regioisomers 13a and 14a (13a,14a/15a,16a ¼ 66/34) but 3-pyridine (5e) 3 4 ( 7ae) revealed a good diastereoisomeric ratio of 92 : 8 (13a : 14a, entry 2). 20 Eventually, to prevent the detrimental effect of an external base, the multicomponent KaMC reaction was effected by chiral isourea 12 and native Meldrum's acid 4 to give similar outcomes (entry 3).…”

“…14 Eventually, in order to exploit the full potential of the diastereoselective MCR strategy (Scheme 5), the possibility to cleave the chiral auxiliary of 13a was demonstrated to provide a readily access to enantiopure dihydrouracyl 17. 18,23…”

An easy route to 2‐substituted‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones and 7‐ones starting from the corresponding 2‐amino‐2‐oxazolines

“…Structural elucidation of 2a-b was achieved by 1 H and 13 C nmr on the basis of previous results for the 2-aryl-2,3dihydrooxazole[3,2-a]pyrimidin-7-one series published by Agami et al [5][6][7]. The 1 H nmr spectrum of 2a showed, at 5.75 ppm, the characteristic singlet for the proton at position 6, whereas it was found at 5.89 ppm for 3a.…”

“…Much effort has been devoted to simplify the structures leading to the synthesis of various acyclonucleosides. New pyrimidinones have been defined as synthons to produce new classes of acylnucleosides by reaction with the appropriate nucleophiles [5][6][7]. We have recently developed the preparation of related bicyclopyrimidinones based on the reactivity of the amidine moiety of 2-amino-2-oxazolines [8][9].…”