Azabicyclic systems synthesis

Synthesis of azabicyclic systems using nitrogen-directed radical rearrangements 070BC3071. 

Useful synthetic methodologies are based on the cyclization or rearrangement of the nitrogen-centered radicals generated in the reaction of the appropriate amides with (diacetoxyiodo)benzene in the presence of iodine [652-655]. Specific examples are illustrated by the synthesis of bicyclic spirolactams 622 from amides 621 [653] and preparation of the oxa-azabicyclic systems (e.g., 624) by the intramolecular hydrogen atom transfer reaction promoted by carbamoyl and phosphoramidyl radicals generated from the appropriately substituted carbohydrates 623 (Scheme 3.244) [654],... 

A novel approach to azabicyclic ring systems, based on an epoxide-initiated electrophilic cyclization of an alkyl azide, has been developed by Baskaran. A new stereo- and enantioselective synthesis of the 5-hydroxymethyl azabicyclic framework 91a, present in (+)- and (-)-indolizidines 167B and 209D, for example, was... 

In 1996, Fuchs and Jin (85), continuing to exploit the chemistry of vinyl sulfones, reported a stereospecific synthesis of the azabicyclic ring system of the cephalotaxine ring by means of palladium(0)-mediated aminospiro-cyclization of tertiary allylic sulfones, as shown in Scheme 53. Treatment of compounds 305 and 306 with either triethylamine or tetramethylguanidine (TMG) in the presence of Pd(Ph3P)4 produced the spiro azabicycles 307 and 308, respectively. The tertiary allylic sulfone 309, under identical reaction conditions, yielded 310, which contains the A/CVD ring system of cephalotaxine. 

Ito T, Overman LE, Wang J. Enantioselective synthesis of angularly substituted 1-azabicyclic ring systems dynamic kinetic resolution using aza-Cope rearrangements. J. Am. Chem. Soc. 2010 132(10) 3272-3273. 

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