Pd-Catalyzed Cross-Coupling Reaction of Sterically Hindered Vinyl Iodides and Organozinc Reagents. Synthesis of Vitamin D Analogues with an Aromatic Ring Attached at C-17

Abstract

Palladium-catalyzed coupling of steroid 17-iodo-6β-methoxy-3α,5-cyclo-5α-androst-16-ene (4) 17-iodoandrosta-5,16-dien-3β-ol (5), and structurally similar (3aS,7R,7aR)-benzenesulfonyl-3-iodo-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-indene (6) with various arylzinc chlorides, which were generated from aryl bromides 8 [1-bromomethylbenzene (8a), O-(triethylsilyl-2-bromophenyl)propan-2-ol (8b), 2-(4-bromophenyl)propan-2-ol (8c), 4-bromobenzonitrile (8d), 4-bromobenzoic acid methyl ester (8e), 4-bromobenzoic acid tert-butyl ester (8f) and 3-bromopyridine (8g)] via aryllihium derivatives (the Negishi coupling) was examined. The respective cross-coupling products were obtained in good yields for all aryl bromides except of 8c and 8e. Building blocks for synthesis of certain vitamin D analogues have been prepared.

Synthesis of 17-epi-Calcitriol from a Common Androstane Derivative, Involving the Ring B Photochemical Opening and the Intermediate Triene Ozonolysis

“…The starting material olefin 7 was prepared by reduction of 17-iodo-3α,5-cyclo-5α-androst-16-ene with sodium in ethanol . Initial experiments on cyclopropanation of 7 with alkyl diazoesters and various catalysts indicated that palladium(II) acetate compares well with the more often used catalyst rhodium(II) acetate so it was applied in all further work.…”

Steroids: reactions and partial synthesis

“…52 The availability of 17-iodo-16-enes from the 17-hydrazones has led to their use in various copper and palladium catalysed coupling reactions. [53][54][55] The anti-androgenic and inhibitory action against testosterone 5α-reductase of some 16-bromo and 16-methyl analogues of trenbolone, e.g. 28, has been explored.…”

Transition-Metal-Catalyzed Reactions in Steroid Synthesis

“…The palladium-catalyzed coupling of 17-iodo-6β-methoxy-3α,5α-cyclo-androst-16-ene and 17-iodo-androsta-5,16-dien-3β-ol with various arylzinc chlorides, which were generated from aryl bromides (1-bromomethylbenzene, O -(triethylsilyl-2-bromophenyl)propan-2-ol, 4-bromobenzonitrile, 4-bromobenzoic acid tert -butyl ester, and 3-bromopyridine) via aryllithium derivatives, was examined. The respective cross-coupling products were obtained in good yields …”

“…The respective crosscoupling products were obtained in good yields. 90 During the quest for efficient inhibitors of human cytochrome P450 17R (17R-hydroxylase-C 17,20 -lyase), which is a key enzyme in androgen hormone biosynthesis, a number of 17-pyridyl-androstenes were synthesized. 91 The question was how the pyridyl substituent could be incorporated into the steroidal In the syntheses of the 2-and 4-pyridyl derivatives, a novel palladium catalyst, bromo-(isopropenyl)bis-(triphenylphosphine)palladium(II), prepared from 2-bromopropene and (Ph 3 P) 4 Pd was used.…”