Radical rearrangements are important transformations in organic synthesis. The stabilisation of alpha-nitrogen radicals is shown to be a useful effect for the control of radical rearrangements and is applied to the synthesis of a variety of azabicyclic frameworks. The utility of this method is illustrated in the synthesis of bioactive targets.

E n a n t i o e n r i c h e d 2 -A z a n o r b o r n e n e s f r o m 7 -A z a n o r b o r n a d i e n e s Abstract: 3-exo-Substituted 2-azabenzonorbornenes are accessible from 7-azabenzonorbornadienes in good yields and high enantiomeric excess via asymmetric hydroboration-oxidation, followed by tandem deoxygenation-rearrangement-electrophile trapping and also provide access to substituted aminomethylindenes.Radical cascade processes constitute a powerful methodology for the fast assembly of complex molecular frameworks. 1 We previously demonstrated the synthetic utility of nitrogen-directed radical rearrangements, 2 and recently applied this concept in a neophyl-type rearrangement process (4 → 5) to obtain racemic 2-azabenzonorbornenes, e.g. 6, using xanthates 3 of 7-azabenzonorbornenols 2 (Scheme 1). 3 To build on this latter methodology we sought firstly to develop an asymmetric entry and secondly to trap the rearranged radical 5 with an electrophile in tandem with the deoxygenation-rearrangement. Scheme 1 Reagents and conditions: (a) 9-BBN, THF, 20 °C, 24 h, then NaOH, H 2 O 2 , 0 °C → 20 °C, 90 min; (b) KH, THF, then CS 2 , then MeI; (c) (Me 3 Si) 3 SiH, AIBN (slow addition), PhMe, reflux, 2 h.To examine the first objective, initial studies were undertaken screening ligands in rhodium-catalysed asymmetric hydroboration-oxidation 4 for desymmetrisation of 7-azabenzonorbornadiene 1. However, yields and ees for alcohol 2 could not be optimised to synthetically useful levels. 5 Alkene hydroboration-oxidation using organoboranes derived from a-pinene has been shown to be useful for the preparation of alcohols in high ee, 6 and (-)-diisopinocampheylborane [(-)-Ipc 2 BH] has recently been successfully applied to the structurally related tropenone framework. 7 We envisaged that, by analogy, asymmetric hydroboration-oxidation of readily available benzyne/NBoc-pyrrole cycloadduct 1 8 might generate alcohol 2 in good ee. We were pleased to discover that hydroborationoxidation with 1.5 equivalents (-)-Ipc 2 BH, [prepared from commercial (+)-a-pinene of 92% ee according to the method of Brown] 9 furnished alcohol (-)-2 in 84% yield and 95% ee (Equation 1). 10

Tandem deoxygenation-neophyl-type radical rearrangement-electrophile trapping using xanthates from 7-azabenzonorbornadienes gives 3-exo-substituted 2-aza-5,6-benzonorbornenes, which in some cases undergo isomerisation to (aminomethyl)indenes. The starting xanthates are accessible in good yields and high enantiomeric ratios via asymmetric hydroboration of (aryne/pyrrolederived) 7-azabenzonorbornadienes. Oxidation (using RuO 4 ) and Birch reduction of the 2-aza-5,6-benzonorbornenes provide access to substituted pyrrolidines and tetrahydroindenes, respectively.

Trapping. -Asymmetric hydroboration of substrates (I) gives the alcohols (II) with excellent enantioselectivity. The xanthate (III) derived from (IIa) undergoes an interesting deoxygenative rearrangement-electrophilic trapping to yield the 3-exo substituted 2-azanorbornenes (V). Xanthates (VII) and (IX) derived from (IIb) and (IIc), resp., afford indenes (VIII) and (X) under similar conditions. -(HODGSON*, D. M.; WINNING, L. H.; Synlett 2006, 15, 2476-2479; Chem. Res. Lab., Dep. Chem., Univ. Oxford, Oxford OX1 3TA, UK; Eng.) -Mais 05-116

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