Nucleophilic Ring-Opening of Epoxide and Aziridine Acetates for the Stereodivergent Synthesis of β-Hydroxy and β-Amino γ-Lactams

Abstract

A highly regio- and stereoselective synthesis of novel β,γ-disubstituted γ-lactams with either an anti or syn relative configuration was developed from readily available epoxide and aziridine acetates. The key steps include the regio- and diastereocontrolled nucleophilic ring-opening of these three-membered heterocycles followed by mild reductive cyclization of the γ-azido ester intermediate. The method was also extended to an asymmetric synthesis of (4R,5S)-4-hydroxy-5-phenylpyrrolidin-2-one from a chiral epoxide acetate. The main features of this versatile synthesis of functionalized γ-lactams include the involvement of inexpensive reagents and mild conditions together with high chemical efficiency.

Highly Functionalized 1,2–Diamino Compounds through Reductive Amination of Amino Acid-Derived β–Keto Esters

“…The J 4,5 in derivatives 7a , 7c and 8a (∼6.5 Hz) was higher than in their corresponding distereoisomers 7b and 8b (∼4.5 ppm). Knowing that in this type of heterocyclic system the coupling constant are J anti < J syn [38], we can anticipate the syn - and anti -relative stereochemistry for isomers a ( c ) and b , respectively. Similarly, NOE experiments indicated a syn -relationship between H4 and H5 protons in 7a , 7c and 8a and an anti -disposition in the respective isomers b .…”

Stereodivergent routes in organic synthesis: marine natural products, lactones, other natural products, heterocycles and unnatural compounds

“…Diastereodivergent routes to β-hydroxy-γ-lactams have been reported by Sá and co-workers 92 from epoxide acetates, obtained by epoxidation of β,γunsaturated esters. In the case of the epoxide acetate depicted in Scheme 59, a direct opening with NaN3 gave the anti-β-azido alcohol, which by hydrogenolysis underwent reductive cyclization to give the trans-β-hydroxy-γ-lactam.…”

Ring Expansion of Epoxides under Brønsted Base Catalysis: Formal [3+2] Cycloaddition of β,γ‐Epoxy Esters with Imines Providing 2,4,5‐Trisubstituted 1,3‐Oxazolidines

“…Enantioenriched epoxides 1a and 1f, which have an aryl and an alkyl substituent, respectively,were easily synthesized by Shis protocol. [14] Thet hus synthesized enantioenriched epoxides were subjected to the reaction conditions,a nd the corresponding enantioenriched 2,4,5trisubstituted 1,3-oxazolidines were formed without erosion of the enantiomeric purity.W hereas in principle,f rom am echanistic point of view,t he reaction of enantioenriched alcohols 4 with imines 2 would also allow the synthesis of the same compounds,t his methodology has an advantage due to the high accessibility of enantioenriched epoxides 1 as substrates compared to the corresponding enantioenriched alcohols 4. [15] Finally,t he transformation of 1,3-oxazolidine 3aa was performed (Scheme 6).…”