Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

Abstract

Summary N-Alkenyl ureas and N-alkenyl carbamates, like other N-acyl enamines, are typically nucleophilic at their β-carbon. However, by incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation products that may be deprotected in situ to provide a new connective route to hindered amines.

Regio- and stereoselective intermolecular carbolithiation reactions

“…N-t-butoxycarbonyl propenyl carbamates 106 were also carbolithiated, protonated and deprotected in a one-pot synthesis of amines (Scheme 35b). 52 While E-106 provided (AE)-107 in high 95 : 5 d.r. in only 1 hour, the Z isomer of the bsubstituted vinyl carbamate 106 resulted less reactive providing the carbolithiation product aer 24 hours and, aer hydrolysis, the epi-107 diastereoisomer in lower 80 : 20 d.r.…”

“…Additionally, N-alkenyl carbamates 104 have been shown to be useful substrates for carbolithiation with primary, secondary, and tertiary alkyllithium reagents (Scheme 35a). 52 In an attempt to induce stereoselectivity in the carbolithiation process the (À)-menthyl carbamate was employed as substrate. However, no diastereoselectivity was observed.…”

“…N-Alkenyl ureas 122 also exhibited Umpolung reactivity undergoing facile addition of alkyllithium at their b-carbons (Scheme 43). 52 When the reaction was performed in THF at À78 C or, more easily, by using hindered alkyllithium, the carbolithiation products 124 were obtained in moderate to good yields (47-77%). 52 The carbolithiation reaction of N-alkenyl ureas bearing an N-aryl substituent in THF at À50 C was coupled with N / C aryl transfer within the lithiated urea intermediate, giving rise to rearranged products 123, in good to excellent yields (72-96%).…”

“…52 When the reaction was performed in THF at À78 C or, more easily, by using hindered alkyllithium, the carbolithiation products 124 were obtained in moderate to good yields (47-77%). 52 The carbolithiation reaction of N-alkenyl ureas bearing an N-aryl substituent in THF at À50 C was coupled with N / C aryl transfer within the lithiated urea intermediate, giving rise to rearranged products 123, in good to excellent yields (72-96%). 60 Migration of a phenyl ring is generally faster and cleaner than migration of other substituted aryl groups, such as the electron-rich ones, and using less hindered alkyllithium.…”

Intramolecular vinylation of carbanions using N-acyl benzomorpholines as masked vinylureas and vinylcarbamates

“…[7][8][9][10][11] Building on our discovery that metallated N-benzyl-N'-aryl ureas, [12][13][14][15][16][17][18][19] carbamates, [20][21][22][23] and thiocarbamates [24][25][26] undergo stereospecific aryl migration to the carbanionic centre, we previously reported that the stereospecific N to C vinyl migration of a variety of lithiated benzylic ureas 3, carbamates 4 and thiocarbamates 5 may be used to generate -vinyl tertiary amines, alcohols and thiols from their parent compounds 1 after deprotection of the products 6-8 (Scheme 1a). [27] The N-vinyl substituted starting materials [14,17,[27][28][29][30] for this reported vinylation had been synthesized by a two-step procedure that employed vinyl isocyanate 2 to introduce the N-alkenyl substituent. Unfortunately, 2 is of limited commercial availability because of its toxicity and poor stability towards polymerisation.…”