The intimate connection between metallaborane chemistry and organometallic chemistry is expressed in the existence of isoelectronic pairs of compounds, for example, [(CO) 4 -FeB 2 H 5 ] À 2] versus [(CO) 4 Fe(h 2 -C 2 H 4 )] and [(h 5 -C 5 H 5 )-CoB 4 H 8 ] [3] versus [(h 5 -C 5 H 5 )Co(h 4 -C 4 H 4 )]. [4±8] One of the fascinating aspects of these inorganic analogues of organo-Scheme 2. Formal total synthesis of ()-anatoxin-a (1). See reference [10] for abbreviations. a) PDC, CH 2 Cl 2 , 100 %; b) 1. aq PhCH 2 NH 2 (40 %), p-TsOH (30 mol %), ~; 2. H 2 SO 4 (10 %), 81 % over two steps; c) PhCH 2 -OCOCl, Sc(OTf) 3 (5 mol %), iPr 2 NEt, MeCN, 95 %; d) (R,R)-7 ´HCl, nBuLi (2 equiv), (PhO) 2 POCl, THF, À 100 8C, 89 %, 89 % ee; e) [Pd(PPh 3 ) 4 ], CH 2 CH(OEt)SnBu 3 , LiCl, THF, ~, 84 %; f) 45 % HBr in AcOH, 95 %; g) Pd/C, H 2 , MeOH, (tBuCO) 2 O, 89 %.
quenching of the reaction mixture with diphenyl chlorophosphate gave the enol phosphate 11 with high enantioselectivity (89 % ee). [13] Completion of the formal synthesis was achieved by a Stille reaction of enol phosphate [14] 11 with CH 2 CH(OEt)SnBu 3 in the presence of [Pd(PPh 3 ) 4 ] and LiCl in THF, followed by a novel cascade reaction. This sequence entailed unmasking the enone moiety with concomitant nitrogen deprotection and intramolecular conjugate addition to give the required bridged azabicycle. [15] Changing the protecting group from benzyl to tert-butoxycarbonyl gave ketone 13, which was identical, by 1 H and 13 C NMR, and IR spectroscopy and MS, to that reported by the group of Rapoport. [4] The [a] 22 D value we obtained ( 47.2, c 0.8 in CH 2 Cl 2 ) is consistent with the production of the natural enantiomer ([a] 22 D 51.9, c 0.795 in CH 2 Cl 2 ). [4] Ketone 13 has been converted into ()anatoxin-a (1) by Rapoport et al. in three steps.
In conclusion, this paper describes one of the most concise and efficient routes (34 % overall yield, including the final literature steps) to enantiomerically enriched ()-anatoxin-a. Key steps in our synthesis include a highly enantioselective desymmetrization of an eight-membered ring ketone, and a novel cascade reaction to set up the 9-azabicyclo[4.2.1]nonane skeleton. Such desymmetrization reactions of medium and perhaps large ring ketones could find wide applications in synthesis.