Cyclopropanation Reactions of Pyroglutamic Acid-Derived Synthons with Akylidene Transfer Reagents

Abstract

The cyclopropanation of unsaturated lactams 1 and 3 derived from pyroglutamic acid with nucleophilic alkylidene transfer reagents is investigated. Good-to-modest yields of cyclopropanes were obtained with most sulfur ylides explored. Syn/anti selectivity was found to be dependent on the synthon as well as the sulfur ylide. This cyclopropanation methodology is used in the synthesis of arginine and glutamic acid analogues.

Asymmetric Sulfonium Ylide Mediated Cyclopropanation: Stereocontrolled Synthesis of (+)‐LY354740

“…Indeed, Payne reported the first ever example of enone cyclopropanation by using ylide 4, but only low diastereoselectivity was observed for the cyclopropanation of cyclohexenone at an elevated temperature (Scheme 7). [48,49] The low diastereoselectivity observed in Scheme 10a and b had been rationalized from the assumption that the high diastereocontrol achieved in the initial addition had been subsequently scrambled by betaine equilibration. [3] If ring closure is slowed down by other means, then betaine equilibration and high diastereoselectivity can still be achieved even at high temperatures.…”

Efficient Synthesis of Cyclopropane‐Fused Heterocycles with Bromoethylsulfonium Salt

“…[35] Deprotection and oxidation of 6l gave the conformationally locked glutamic acid analogue (Scheme 5). [36] 63%.…”

An Improved Synthesis of 3,4‐(Aminomethano)proline and Its Incorporation into Small Oligopeptides

“…[5] The 1Ј,1Ј-dimethyl-(4) and 1Ј-guanidinylmethyl-(5) as well as 2 have been used for an extensive study of peptide mimics based on the 3,4-methanoproline system ( Figure 1). [6] 4440 tide synthesis with the Fmoc strategy. Thus, the features of Amp as a γ-amino acid residue (γ-Amp) were investigated in the preparation of alternating α/γ-amino acid sequences.…”

“…These results are encouraging for the development of foldamers based on γ-Amp units. Recently, we described the first synthesis of 3,4-(aminomethano)proline (6). [7] Starting from (2S,4R)-N-Boc-4-hydroxyproline, protected 3,4-(aminomethano)proline could be obtained in a remarkably short synthesis of four steps only, furnishing a single diastereomer of this diamino acid.…”