Geometry-Selective Synthesis of E or Z N-Vinyl Ureas (N-Carbamoyl Enamines)

Abstract

N-Vinyl ureas are emerging as a valuable class of compounds with both nucleophilic and electrophilic reactivity. They may be made by capturing the enamine tautomer of an imine with an isocyanate, a reaction which in general leads to the E isomer of the vinyl urea. Deprotonation of such a vinyl urea, or of an allyl urea, generates a dipole stabilized Z-allyl anion which may be protonated to return the Z-vinyl urea. Isomerization of an allyl urea with a Ru complex provides an alternative route to E-vinyl ureas.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…Nevertheless, substituents present in the Ar 1 ring or the aryl ring of the substrates 42 had negligible effects on the reaction(Scheme 70). [112] Schneider and co-worker reported an enantioselective organocatalytic domino vinylogous Michael/ Knoevenagel-type condensation reactiono fb is-silyl-1,3-dienediolate 266 and a,b-unsaturated aldehydes 42.T he reactionf urnished 1-cyclopentenyl-a-keto esters 268 in moderate to good yields andw ith excellent enantioselectivities via the intermediates 267 (Scheme 71). [113] Several synthetic transformationsu tilizing the multiplef unctional groups in 268 were further performed.…”

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

“…Simple N -alkenyl ureas 1 were prepared by a reported method [2] entailing N-acylation of an acetophenimine with an isocyanate, followed by N-alkylation of the resulting urea. When urea 1a was treated with t -BuLi or s -BuLi in THF at −78 °C for one hour, followed by protonation, carbolithiated products 2a and 2b were isolated in good yield (Scheme 1 and Table 1, entries 1 and 2).…”

“…β-Substituted vinyl ureas 3 are available as either E or Z geometrical isomers according to the method of synthesis: N-acylation of a propiophenimine typically generates an E -alkenylurea, but deprotonation and reprotonation of the urea inverts its geometry to Z [2], probably via an intramolecularly chelated urea-substituted allyl anion [17]. Urea E - 3a was treated with n -BuLi in Et 2 O (the less-coordinating solvent suppresses rearrangement of the product [4]) at −40 °C: it underwent clean carbolithiation of the double bond, and on protonation urea 4a was obtained as a single diastereomer in 85% yield (Scheme 2 and Table 2, entry 1).…”

“…E - 10 was isomerised to Z - 10 by treatment with LDA and reprotonation (presumably, like the equivalent ureas [2–3], via an intramolecularly coordinated Z -allyllithium [21–22]), giving Z - 10 in excellent yield (Scheme 4). However, in contrast to Z -alkenyl ureas, Z - 10 was rather less reactive than its E -isomer.…”

“…Enamines and N -acyl enamines are in general nucleophiles, reacting with electrophiles at the carbon atom β to the nitrogen atom [1–2]. The resulting intermediate iminium or N -acyliminium ions are electrophilic, and may themselves trap a nucleophile at the position α to the nitrogen substituent.…”