Asymmetric syntheses of polysubstituted homoprolines and homoprolinols

Asymmetric Synthesis of the Tetraponerine Alkaloids

“…The remaining tetraponerine alkaloids in the series, based on a decahydro­dipyrrolo­[1,2- a :1′,2′- c ]­pyrimidine scaffold 1 (i.e., tetraponerines 1, 2, 5, and 6), were targeted next. Dihydropyrrole 36 was prepared via a known sequence of reactions, , involving conjugate addition of lithium ( R )- N -allyl- N -(α-methylbenzyl)­amide ( R )- 4 to tert -butyl sorbate 3 , which gave β-amino ester 35 in 89% yield as a single diastereoisomer (>99:1 dr). Subsequent ring-closing metathesis of 35 gave dihydropyrrole 36 in 86% yield and >99:1 dr. , In this case, it was found that hydrogenation of 36 with Wilkinson’s catalyst [RhCl­(PPh 3 ) 3 ] ,, to give pyrrolidine 37 was necessary to avoid oxidative side reactions, leading to various pyrrole containing species, in the subsequent steps .…”

“…Dihydropyrrole 36 was prepared via a known sequence of reactions, , involving conjugate addition of lithium ( R )- N -allyl- N -(α-methylbenzyl)­amide ( R )- 4 to tert -butyl sorbate 3 , which gave β-amino ester 35 in 89% yield as a single diastereoisomer (>99:1 dr). Subsequent ring-closing metathesis of 35 gave dihydropyrrole 36 in 86% yield and >99:1 dr. , In this case, it was found that hydrogenation of 36 with Wilkinson’s catalyst [RhCl­(PPh 3 ) 3 ] ,, to give pyrrolidine 37 was necessary to avoid oxidative side reactions, leading to various pyrrole containing species, in the subsequent steps . Reduction of the ester moiety within pyrrolidine 37 with DIBAL-H followed by in situ Wittig reaction of the corresponding aldehyde with Ph 3 PCHCO 2 t Bu gave a 75:25 mixture of 38 and 39 , respectively.…”

“…Our divergent synthetic strategy toward the tetraponerine alkaloids involved two iterative lithium amide conjugate additions to install the requisite stereochemistry. In the first instance, conjugate addition of either lithium ( R )- N -allyl- N -(α-methyl­benzyl)­amide ( R )- 4 ( n = 1) or lithium ( R )- N -(but-3-en-1-yl)- N -(α-methyl­benzyl)­amide ( R )- 5 ( n = 2) to tert -butyl sorbate 3 , − followed by ring-closing metathesis of the resultant N -alkenyl β-amino ester 6 ( n = 1 or 2) and homologation, would give the key α,β-unsaturated ester 7 ( n = 1 or 2). Subsequent conjugate addition of the requisite antipode of lithium N -benzyl- N -(α-methylbenzyl)­amide 8 to α,β-unsaturated ester 7 ( n = 1 or 2) would then provide a range of diamines 9 and 10 ( n = 1 or 2 in both cases) for elaboration.…”

A Short Synthesis of (2S,3S,4R)-Dihydroxyhomoprolines from d-Erythrose-Derived 5,6-Dihydro-2H-pyran-2-one

“…7 In contrast, very few investigations have focused on the -amino acid congeners; only two papers have appeared recently, published by the Davis group. 8,9 In this work a 1,5-lactone 1, obtained from D-erythrose, 10 is used as a remote chiral synthon for the syntheses of the title (2S,3S,4R)-dihydroxyhomoprolines 2. In previous work, primary amines and sulfides were added to 1, and the mechanism of the addition reaction was studied computationally.…”