Acylamino radicals

The placement of heteroatoms adjacent to the radical center often slows the rate of cyclization and, although low concentration techniques are required, good yields of cyclic products can still be obtained. Hart s systematic studies on the cyclizations of acylamino radicals were among the first to demonstrate the preparative utility of radical cyclizations.78 Scheme 19 provides some recent examples. In general,... 

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... 

The preparation of alkaloids (cyclic compounds containing nitrogen atoms) is very important, as most alkaloids are biologically active. Eq. 3.10 shows the preparation of alkaloids (27), a precursor of gephyrotoxin, via an a-amino radical formed from y-thiophenoxylactam (26). Other alkaloids such as indolizidine and pyrrolizidine can be also prepared similarly via a-amino radicals and a-acylamino radicals. 

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). 

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,... 

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>. 

Two separate syntheses of ( - - )-heliotridine (850) employ the strategy of an intramolecular addition of an a-acylamino radical to an alkyne (Scheme 125) [188,189]. Selective reduction of 857 to 858 followed by acetylation (859) and acetoxy-thiophenoxy exchange affords the radical precursor 860. 

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

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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