Desymmetrization of meso‐Bicyclic Hydrazines by Rhodium‐Catalyzed Enantioselective Hydroformylation

Abstract

An asymmetric hydroformylation of three meso-bicyclic hydrazines followed by the reduction of the formyl product afforded the corresponding desymmetrized optically enriched hydroxymethyl hydrazines (up to 77.5 % ee).

Asymmetric Hydroformylation of an Enantiomerically Pure Bicyclic Lactam: Efficient Synthesis of Functionalised Cyclopentylamines

“…Although internal alkenes can be sluggish hydroformylation substrates, strained alkenes often show good reactivity, as demonstrated by recent studies on the hydroformylation of norbornene and bicyclic hydrazines. [15] Therefore, we turned our interest to attempting hydroformylation of the bicyclic lactam azabicyclo-[2.2.1]hept-5-en-3-one (1) (see Scheme 1), because there is a significant demand for functionalised cyclopentylamines that potentially could be accessed by using this reaction. This demand arises from the widespread use of carbocyclic nucleoside analogues in medicinal chemistry; [16] a considerable range of compounds of this general type are biologically active, including clinically applied drugs and drug candidates, most notably, the widely applied nucleoside analogue reverse transcriptase inhibitor Abacavir, used to treat HIV and AIDS.…”

Desymmetrizing Hydroformylation of Dihydromuconic Acid Diesters: Application to the Synthesis of (±)-Vindeburnol

“…Besides the work developed by Breit et al on the desymmetrizing hydroformylation of dialkenylcarbinols (terminal double bonds), few examples of the desymmetrizing hydroformylation of internal double bonds have been described. What is known includes the following: the hydroformylation of symmetric bicyclic hydrazines for the synthesis of prostaglandin endoperoxide analogues, , the synthesis of perhydrofuro­[2,3- b ]­furans and perhydrofuro­[2,3- b ]­pyrans by hydroformylation of α,ω-alkenediols, the hydroformylation applied to 1,4-diacetoxy-2-butenes for the synthesis of vitamin A , based on both BASF and Hoffmann-La Roche processes, and work on the desymmetrizing hydroformylation of cyclopropenes and cyclopentenes . In this paper, a desymmetrizing hydroformylation of internal double bonds of dihydromuconic acid diesters is described (Scheme ).…”

“…±)-(4 1 S*,12S*,13aR*)-2,3,41 ,5,6,12,13,13a-Octahydro-1Hindolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridin-12-ol ((±)-Vindeburnol) 25. R f : 0.21 (5% MeOH in AcOEt).…”