Allylation of amino-acid esters gives rise to intermediate quaternary ammonium salts, which undergo proton abstraction to give ylides and [2,3]-sigmatropic rearrangement. The resulting aamino-acid derivatives can be subjected to N-deallylation to provide a rapid access to a-allyl-a-amino-esters. Using N-benzyl proline methyl ester, chirality transfer from carbon to nitrogen then back to carbon takes place.The preparation of unnatural amino-acids and their derivatives continues to attract considerable research interest. 1 This is due in part to their use as sources of ligands for catalytic reactions or their incorporation within peptides or analogues in order to confer desirable properties such as conformational restriction. We have reported recently a new approach to amino-acids by N-alkylation of N-allyl a-amino-esters. 2,3 The resulting quaternary ammonium salts rearrange, after ammonium ylide formation, by a [2,3]-Stevens rearrangement. For example, the allyl glycine derivative 2 can be formed using a one pot N-alkylation-ylide formation-rearrangement protocol from the amine 1.The [2,3]-Stevens rearrangement of ammonium ylides is known using a variety of N-allyl quaternary ammonium salts and basic conditions, although the use of simple Nallyl a-amino-esters is rare. 4 The combined N-alkylation, ylide formation and rearrangement strategy (e.g. 1 to 2, Scheme 1) occurs under mild conditions and avoids the need to isolate the ammonium salt, providing N,N-dialkylated a-amino-acid derivatives from N-allyl a-amino-esters in one pot. A drawback of this method, however, is the necessity to prepare the starting materials from the Nunsubstituted a-amino-esters and the inability to convert the product to the a-amino-acid derivatives which are unsubstituted on the nitrogen atom. In this paper we report a more convenient approach to a-amino-acid derivatives using this type of chemistry, starting from simple esters of natural amino acids and leading, after N-deallylation, to N-unsubstituted a-amino-esters.Taking the simple glycine methyl ester as the starting material, allylation with excess allyl bromide under the conditions described above, resulted in the formation of the [2,3]-Stevens product 4 (Scheme 2). Tri-allylation on the nitrogen atom generates the intermediate quaternary ammonium salt, which undergoes proton abstraction to the ylide 3 and rearrangement to give the a-amino-acid derivative 4. We were pleased to find that the N-allyl groups could be cleaved selectively using palladium(0) 5 to give the primary amine 5 (Scheme 3). This method therefore allows a rapid (two step) preparation of allyl glycine methyl ester from the simple glycine methyl ester. 6 Scheme 2 Scheme 3The allylation and in situ rearrangement of various simple a-amino-esters was investigated as outlined in Table 1. Allyl iodides, bromides or chlorides could be used successfully. Slight improvements to the yields were obtained by adding Bu 4 NI to the reactions with allyl bromide. The use of crotyl chloride gave the allyl-transposed product 7c (...

Methods have been developed for the N-alkylation of 1,2,4-dithiazolidine-3,5-dione 2 and the subsequent conversion of the N-alkylated derivatives into isocyanates 5. An extension of this methodology onto a solid-support is also reported. X-ray crystallographic analysis has been carried out on potassium 1,2,4-dithiazolidine-3,5-dione 3 for structural comparison with the parent heterocycle 2.

Dithiazolidine-3,5-dione 1 can be used as a nitrogen nucleophile in a modified Mitsunobu procedure to give N-alkylated products 2 which can be converted via isocyanates, into amine derivatives, under very mild conditions.

Other 5-membered heterocycles R 0330A Stereocontrolled Route to Protected Isocyanates from Alcohols. -Dithiazolidine (II) provides an excellent isocyanate synthetic equivalent in Mitsunobu-type reactions using a wide variety of alcohols. In the presence of a thiadiazolidine betaine reagent, compound (II) affords the corresponding N-alkylated products with inversion of configuration, which is incomplete in some cases. A number of the products are converted, through intermediate isocyanates, into N-protected amines (V), (IX) and (X). -(CANE-HONEYSETT, D. J.; DOWLE, M. D.; WOOD*, M. E.; Tetrahedron 61 (2005) 8, 2141-2148; Dep. Chem., Univ. Exeter, Exeter, Devon EX4 4QD, UK; Eng.) -Klein 26-078

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