Enamides radical acceptor

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. 

Two other syntheses that involve enamides as radical acceptors are shown in Eqs. (25) and (26). Clive has reported syntheses of the ACE inhibitors A-58365 [57] and A-58365B [58]. The latter synthesis involved preparation of enamide 89 via a short reaction sequence, followed by a triphenyltin hydride-initiated addition-... 

In addition to the well exploited radical additions to enamides, thiovinyl ethers have been shown to be suitable intramolecular acceptors for aryl radicals. By placing a thiophenyl substituent on terminal alkene of 33, the cyclization to 34 occurred exclusively in the 6-exo mode and was not complicated by internal hydrogen abstraction from the allylic positions of the alkene (Scheme 13) [83, 84]. 

The azetidinone ring system 43 is an important structural feature of the powerful b-lactam famiUes of antibiotics and appears in many other natural products such as clavulanic acid. Free radical-based routes to this ring system are remarkable for their variety and range. Four distinct radical-based disconnections have been investigated for azetidinone preparation. Disconnection a impUes closure of a carbamoyl-type radical onto an imsaturated acceptor group. Disconnection b imphes a closure of an amidoalkyl (a-carbamoyl) radical onto an enamide acceptor. Disconnection c points to an amidyl radical ring closure onto an alkene acceptor. Finally, disconnection d connotes ring closure of an acyl radical onto an imine acceptor (Scheme 11). 

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