Synthesis of pyroglutamic acid derivatives via double Michael addition reactions of alkynones.

Abstract

I. Synthesis of pyroglutamic acid derivatives via double Michael reactions of alkynones Pyroglutamic acids and their derivatives are common structural units of widespread chemical significance and they have been heavily utilised as building blocks for asymmetric synthesis. A new method for the synthesis of highly functionalised pyroglutamic acid derivatives, which consists in a Double Michael addition route that utilises amidetethered carbon diacids and aromatic alkynones as substrates, is here described. The reaction proceeds with good levels of trans-diastereoselectivity, provided that substoichiometric quantities of Mg(OTf)2 or Ni(acac)2 are employed. II. Michael additions combined with Friedel-Crafts cyclisations A domino Michael/Friedel-Crafts alkyation of aryl ethers with propargyl ketones was developed as a continuation of our double Michael additions. The reaction, here described, proceeds in good yield over two steps, when the aryl ethers and alkynones are treated with substoichiometric quantities of Yb(OTf)3 and heated to 100 oC in a microwave oven.