Biomimetic Hydroxylation of Nonactivated CH₂ Groups with Copper Complexes and Molecular Oxygen

Abstract

Copper(I) complexes with steroidal ligands (see formula) undergo regio‐ and stereoselective γ‐hydroxylation in the 12β‐position of the steroid in the presence of molecular oxygen. After reduction a 17β,12β‐amino alcohol is obtained. Under hydrolytic conditions a 12β‐hydroxy‐17‐ketone can be isolated.

Steroids as chiral model compounds for selective reactions with metals

“…In the case of the hydrolytic work-up procedure, the iminomethylpyridine (IMPY ligand) and the iminoethylpyridine ligand play an auxiliary role and can be simply removed after the hydroxylation procedure [44,45]. Conformational analysis by X-ray analysis and MMFF94 force field calculations for IMPY compound 42 indicate that a seven-membered ring with six atoms nearly in a plane (Fig.…”

Catalytic Oxidative Processes in Steroid Chemistry: Allylic Oxidation, β-Selective Epoxidation, Alcohol Oxidation and Remote Functionalization Reactions

“…Tri-or bidentate ligands with N-donor atoms for copper complexation covalently attached to the steroid nucleus have been used as directing groups for the regio-and stereoselective hydroxylation of nonactivated C-H bonds of steroid substrates, using molecular oxygen as the oxidant. Hydroxylations in the -position relative to the central Natom occurred in relatively low yields [206]. More recently, Scheme 27.…”

Terpenoid‐Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis

“…37 in the 1960s provided approaches towards cyclopamine ( 9 ), it was not until 2009 that Giannis and co-workers provided its expedient, biomimetic total synthesis (Scheme 2b). 25 Starting with dehydro- epi -androsterone ( 46 ), benzyl protection and condensation gave the 2-picolylimine directing group (Schönecker directing group) 33 on 52 . Treatment with tetrakis(acetonitrilo)copper(I) hexafluorophosphate and molecular oxygen provided the 12β-hydroxyl group functionality that the commercially available core lacked.…”

“…This intermediate could be easily elaborated to “western half” 79 in five steps, delivering not only the oxidized C 18 methyl group but also the Δ 14 moiety. For the eastern region of the molecule, a Schönecker oxidation 33 was employed to activate the C 12 methylene and install the 12β-hydroxyl group. Similar to the cyclopamine synthesis, trans -androsterone ( 50 ) was used and condensed to give the 2-picolylimine.…”