Radical cyclization, with pyroglutamate

Radical cyclization with high diastereoselectivity and high asymmetric induction is possible when chiral precursors are used (as with 174 175 from pyroglutamate). Livinghouse and co-worker reported a chiral... 

A radical cyclization of a 2-chloroacyl enamine 157 was used to synthesize 2-substituted pyroglutamates 160. Usually, the radical 158 undergoes an initial 5-endo cyclization (path a) and the resulting intermediate 159 attacked electrophiles like methyl acrylate to give the pyroglutamate 160. Unexpectedly, the reaction with methyl methacrylate took another course and a seven-membered... 

Very little or no diastereoselectivity was observed in the formation of pyrro-lines 35, whereas somewhat better results were obtained with pyroglutamate 36 (R = er/-Bu), which was formed in a 1 2.5 cisjtrans ratio. An efficient stereocontrol of the key cyclization step was however achieved with suitably designed starting materials bearing a bulky OTBDMS group vicinal to the site of radical addition [22b]. Cyclization of the. syn-isonitrile 39 with either ethanethiol or mer-... 

Cossy has reported a synthesis of a-kainic acid that establishes the stereogenic centers on a preformed pyrrolidine ring (Eq. 20) [40], Thus, ketone 57 was prepared from L-pyroglutamic acid in 11 steps. Samarium iodide-mediated cyclization of 57 gave 58 as a mixture of stereoisomers at the carbinol carbon. Dehydration gave 59, and a 6-step sequence, starting with oxidative cleavage of the double bond, provided a-kainic acid. One notable aspect of this synthesis is the use of an enamide as a free-radical acceptor in the key cyclization. This process has been used in a number of alkaloid syntheses as will be seen in the next section. 

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