Process for carbon-carbon bond formation at the c-4 position...

C - Chemistry – Metallurgy – 07 – D

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C07D 205/08 (2006.01) C07D 205/085 (2006.01) C07D 205/095 (2006.01) C07D 405/12 (2006.01) C07D 409/12 (2006.01) C07D 477/24 (2006.01) C07F 7/10 (2006.01) C07F 7/22 (2006.01)

Patent

CA 1249279

ABSTRACT OF THE DISCLOSURE The invention encompasses a process for stereoselective carbon-carbon bond formation at the C-4 position of a 3-(acylamino)azetidinone. The process is carried out under free radical conditions using a (2- substituted or unsubstituted allyl)tin reagent. The 3- (acylamino)azetidinone is of the general formula Image (II) wherein R5 is an acyl group of the formula Image wherein Rf is (a) C1 to C7 alkyl, cyanomethyl, or 4-pro- tected amino-4-protected carboxybutyl; or (b) C1 to C6 alkoxy, allyloxy, phenoxy, benzyloxy or 4-methoxybenzyloxy; or (c) the group Rg, wherein Rg is phenyl or substituted phenyl, wherein the sub- stituents are one or two halogens, protected hydroxy, cyano, trifluoro- methyl, C1 to C4 alkyl, C1 to C4 alkoxy, protected amino, protected carboxy, protected carboxymethyl, protected hydroxymethyl or protected aminomethyl; or (d) an arylalkyl group of the formula Rg-(O)m-CH2- wherein Rg is as defined above and m is 0 or 1; or (e) a substituted arylalkyl group of the formula Image wherein Rh is Rg as defined above, thien-2-yl, thien-3-yl, fur-2-yl, or fur-3-yl; and W is protected hydroxy, protected carboxy, or protected amino; or (f) a heteroarylmethyl group of the formula Ri-CH2- wherein Ri is thien-2-yl, thien-3-yl, fur-2-yl, fur-3-yl, thiazol-2-yl, tetrazol-5-yl, or tetrazol-1-yl; R6 is hydrogen or methoxy; R8 is hydrogen, an amino protecting group, or a group of the formula Image wherein Rj is a carboxy protecting group; R10 is chloro, bromo, iodo, or a group of the formula -Se-R11 or -S-R11 wherein R11 is C1 to C4 alkyl, phenyl, substituted phenyl, 1-naphthyl or 2-naphthyl; provided that when R10 is a group of the formula -S-R11 , R8 is other than a group of the formula Image ; further provided that, when R10 is a group of the formula -S-R11 or -Se-R1 R6 is other than methoxy.

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