Nucleophilic Additions of 2-Furyllithium to Carbonyl Derivatives of L-Serine. Formal Synthesis of (2R,3R)-β-Hydroxy Aspartic Acid

P Merino,F Merchan,T Tejero,S Franco

doi:10.3390/30100026

Abstract

The nucleophilic addition of 2-furyllithium to esters derived from L-serine is described. The obtained furyl ketone 5 is stereoselectively reduced (ds≥95%) with sodium borohydride to afford the corresponding syn aminoalcohol 12 in enantiomerically pure form. Compound 12 was further converted into valuable α-hydroxy-β-amino acids by means of the furan-to-acid equivalence.

Highlights

Molecules 1998, 3 for the formation of a C-C bond [7]
The reaction of metalated furans with carbonyl compounds constitutes a useful way of introducing the furan ring; in this context, a vast number of examples concerning the addition of metalated furans to aldehydes and ketones can be found in the literature [8]
Only a few reports on the addition of organometallic derivatives of furan to acid derivatives, such as acid halides, esters or amides have been described [9]. In this communication we wish to report our latest efforts at expanding the scope of the synthetic utility of the furan ring

Summary

NBoc OMe

N aReagents and Conditions: i, Boc2O, NaOH, r.t. ii, MeNH(OMe)HCl,WSC, H2O-THF. iii, DMP, acetone, BF3OEt2, r.t. iv, 2-furyllithium, THF, -40 °C. The addition of 1.05 equivalents of 2-furyllithium 1 to hydroxamate 4 in THF as a solvent afforded the expected furyl ketone 5 in only 20% yield after 12 h at -40 °C, a substantial amount of starting material (c.a. 50%) being recovered. Whereas the addition of 2-furyllithium 1 (2.1 equiv., THF, -40 °C) to ester 7 afforded the corresponding ketone 9 in 45% yield, the addition of 1 (1.05 equiv., THF, -40 °C) to ester 8 provided the furyl ketone 5 in 74% yield after 4 h of reaction [14]. In both cases a small amount of starting material (c.a. 10%) was recovered

COOMe ii

OBn OBn