Adducts of α-Lactams and a Dihydro-1,3-Oxazine: A Convenient Synthesis of α-Amino Ketones

Abstract

The reaction of α-lactams (1a–1d) with tert-butyllithium at room temperature to yield α-hydroxy imines (5ax–5dx) was reported by us as the first example of a reaction between an α-lactam and an organolithium reagent.¹ Subsequent investigation revealed that α-amino ketones (4ax–4dx) could be isolated from the reaction mixtures at lower temperatures under very carefully controlled conditions that prevent the rearrangement of 2 and 3.² In fact, a variety of α-amino ketones were synthesized in this fashion,³ a result that was confirmed later by Baumgarten and co-workers.⁴ As part of a broader study of the reactions of a-lactams with organometallic reagents, we investigated the reactions of α-lactams with the lithium salt of 2,4,4,6-tetramethyl-5,6-dihydro-4H1,3-oxazine (6), a reagent that has been extensively used by Meyers⁵ for the synthesis of aldehydes. Although these reactions did not lead to aldehydes under the conditions described by Meyers, we did find them to be convenient routes to α-amino ketones, particularly in view of the complete absence of rearrangements of the type 2 → 3 under avariety of conditions.