A-Acylamino radical cyclization

In general, a-acylamino radicals cyclize with the same relative stereoselectivities as the corresponding all-carbon systems, but with diminished reactivity and regioselcclivity. Thus, in some cases, the 5-exo 6-endo ratios are rather small and significant amounts of reduced noncyclized products are formed60,... 

Hart DJ, Tsai Y-M (1984) a-Acylamino radical cyclizations synthesis of isoretronecanol. J Am Chem Soc 106 8209-8217... 

Indolizidinones pyrrolizidones Reaction of the thiophenoxylactam 1 with n-Bu3SnH (AIBN) results to a minor extent in reduction. The major products result from cyclization of an intermediate a-acylamino radical to a pyrrolizidinone 2 and an indolizidinone 3, in a 2 1 ratio. This ratio of exo and endo cyclization is dependent on... 

PyrroUvdines (11, 546). Intramolecular cyclization of an a-acylamino radical to an allene provides a route to the pyrrolizidine alkaloid supinidine (4), outlined in Scheme (1). 

A synthetic pathway to trachelanthamidine. the C-7 epimer of isoretronecanol, is the radical cyclization of a chiral 2-vinylpyrrolidine derivative72. The atom-transfer cyclization affords the fAot.v-pyrrolidizinone, hence, introducing the opposite relative configuration when compared to the cyclization of the bridgehead a-acylamino radicals. 

Since the first edition several sequences involving construction of the six-membered ring have been published. In most cases these are variations on the well-established, highly diastereoselective cyclizations of A -acyliminium ions <85JOC3243, 86H(24)62l> and a-acylamino radicals <90H(30)263, 91H(32)23ll>. Compound (151) was obtained enantiomerically pure as shown (Scheme 28) <85H(23)395>. Alternative routes to racemic precursors of (151) have been described <83JOC3835, 85SC883>. 

Kano S, Yuasa Y, Yokamatsu T, Asami K, Shiroshi S (1986) Effect of A-strain on synthesis of cis-fiised 4a-aryloctahydro—lH-cyclopenta[c]pyridine derivatives through tandem radical cyclization of an a-acylamino-polyene system. J Chem Soc Chem Commun 1717-1718... 

As mentioned in an earlier section in this Report, free-radical carbon-carbon bond-forming processes are becoming increasingly important in synthesis, and this year they have proved themselves particularly useful for the synthesis of pyrrolizidine alkaloids. Thus, Hart and his group have now applied their intramolecular tin hydride generated ot-acylamino radical to alkyne cyclization [viz. (97) - (98)] and to the synthesis of (-)-dehydrohastanecine (99), (+)-heliotridene (100), and (+)-hastanecine (101). In addition, free radical in mechanism is the photochemical cyclization of the -acylpyrrolidine (102) to the pyrrolizidene (103), a key intermediate in a synthesis of ( )-isoretronecanol (104). 

Construction of C-C bonds adjacent to nitrogen is an important aspect of alkaloid chemistry. A new approach to indolizidines and pyrrolizidines has been developed in which acylamino-radicals (139) cyclize to the required products. ... 

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