Patent ID: 7012142

Claim:
A method of synthesis of a bicyclic or polycyclic compound of formula I or formula II in which: E represents an electrophile; each of R, R 1 , R 2 , R 3 , R 6 , R 7 , R 8 and R 9 independently represents hydrogen, alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, benzylamino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, arylsulphenyl, carboalkoxy, carboaryloxy, mercapto, allcylthio, benzylthio and acylthio, each of which may optionally be substituted, and wherein any two or more of R, R 1 -R 3 and R 6 -R 9 form an optionally substituted alkyl, alkenyl or alkynyl chain, which chain may also optionally include one or more O, N or S atoms therein; Y represents C(R 12 )R 13 , O, NR 14 , or S, wherein R 12 , R 13 and R 14 each independently have the same definition as R; G represents W or X; W represents an electron withdrawing group; X is H; Z represents O, NR 15 , S or CR 16 W′, where R 15 and R 16 each have the same definition as R, and W′ has the same definition as W; and each of n and m represents an integer from 0 to 100; and the method comprises the steps of (a) treating a compound of formula III; in which R, R 1 -R 3 , W, X and Y are as defined above for the compounds of formulae I and II, and R 4 and R 5 each independently have the same definition as R with base to form the corresponding enolate; (b) subjecting a compound of formula W to nucleophilic addition by the enolate form of compound III; in which R 6 -R 11 and Z are as defined above for the compounds of formulae I and II, and R 10 and R 11 each independently have the same definition as R; (c) subjecting the product of step (b) to ring closing metathesis; and (d) subjecting the product of step (c) to stereoselective ring closure by reaction with a reagent selected from the group consisting of HgCl 2 , Hg(OCOR) 2 , Br 2 , Cl 2 , I 2 , RCO 3 H, ArCO 3 H, and PhSeBr.