Brian Tuck

Synthesis of 1-aminoalkylphosphinic acids. Part 2. An alkylation approach

Aminomethylphosphinic acid (7), protected at nitrogen as the imine derived from benzophenone and at phosphorus as the diethylacetal and ethyl ester [i.e. (6)], undergoes facile LDA-induced alkylation. Treatment with primary alkyl halides affords, on product hydrolysis, a versatile route to phosphinic analogues of α-amino carboxylic acids. Analogues of alanine, valine, leucine, phenylalanine, tyrosine, histidine, and aspartic and glutamic acids are thus prepared; the phosphonic histidine analogue (23b) can be prepared similarly from the imine phosphonate diester (21). Intra- and inter-molecular dialkylation reactions provide analogues of 1-aminocyclopropanecarboxylic acid (14) and 2,6-diaminoheptanedioic acid (16). Benzyl bromide alkylation of (25a) and (30a), where the nitrogen is protected as the imine of the 2-hydroxypinan-3-one chiral auxiliary (24) or (29), is diastereospecific leading to asymmetric synthesis of either (+)- or (–)-phenylalanine analogues; this selectivity is compared to that shown by the corresponding chiral imine phosphonate (25b) and imine carboxylate (25c).

Free radical catalysed additions to the double bond of diketene: a synthesis of novel oxetan-2-ones

Free radical-catalysed additions to the exocyclic double bond of diketene are described. Thiols give unstable 4-thiomethyloxetan-2-one adducts which could be oxidised to their more stable sulphoxides or sulphones. Addition of a range of P–H compounds led, with a few exceptions, to stable phosphorus-substituted 4-methyloxetan-2-ones. The radical-catalysed chlorination of diketene by sulphuryl chloride has been shown to give 4-chloro-4-chloromethyloxetan-2-one. Further 4-halogeno-oxetan-2-ones were prepared by addition of halocarbons such as carbon tetrachloride, bromotrichloromethane, and carbon tetrabromide and of trichloromethanesulphenyl chloride to diketene.