E- and Z-Stereoselectivity in the preparation of enamides from glycidyl sulfonamides and carbamates

Abstract

Treatment of glycidyl sulfonamides with LDA delivers the corresponding enesulfonamide with good selectivity for the E-isomer, whereas the corresponding carbamates exhibit selectivity for the Z-enecarbamate. An E1cB elimination mechanism proceeding from a substrate-base chelate complex is advanced as rationalisation of the latter set of Zselective outcomes.Enamides are valuable synthetic intermediates, 1 and their stereoselective preparation has attracted much recent attention from the synthetic community. In this regard, new methods for access to this functional unit have been introduced lately based on, inter alia, cross coupling processes; 2 hydroamination of alkynes; 3 and the Peterson reaction.4 In relation to this and based on our ongoing drug discovery programmes, we wished to prepare a range of enamines of general structure 2, possessing different pendant nitrogen groups. We envisaged that a base-induced epoxide-allylic alcohol rearrangement 5 of the appropriately N-functionalised glycidyl amine 1 would represent an extremely concise entry into this series of compounds from simple starting materials (Scheme 1). Excepting a single example, 6 there have been no reports on this particular reaction variant with acyclic substrates. 7,8Herein, we report our studies leading to substrate dependent stereoselective access to the desired E-and Z-product isomers.Treatment of glycidylamine derivatives 1a-f with excess LDA at -78• C in 2-methyltetrahydrofuran (2-MeTHF), followed by warming to -60• C over 2 h and an aqueous extractive workup, gave the results summarised in Table 1. Other than for the sterically

Transition Metal-Free Cascade Cyclization of Epoxy-Ynamides: To Go for 1,3-Oxazines or 1,4-Oxazines?

“…In a control experiment, the ring expansion reaction of alkyne-free epoxy sulfonamide 4 in the presence of the base KO t Bu (2 equiv) in THF (2 mL) led to product 5 in 46% yield (Scheme a). This part is consistent with a literature report . The reaction of epoxy ynamide 1a with LDA or n -BuLi at −78 °C for 0.5 h resulted in isomeric allyl alcohols ( E + Z )- 6 (ca.…”