Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water

Abstract

A practical and convenient method for the efficient and regio- and stereoselective ring-opening of enantiopure monosubstituted epoxides by sodium azide under hydrolytic conditions is reported. The ring–opening of enantiopure styryl and pyridyl (S)-epoxides by N3− in hot water takes place preferentially at the internal position with complete inversion of configuration to produce (R)-2-azido ethanols with up to 99% enantio- and regioselectivity, while the (S)-adamantyl oxirane provides mainly the (S)-1-adamantyl-2-azido ethanol in excellent yield. In general, 1,2-amino ethanols were obtained in high yield and excellent enantiopurity by the reduction of the chiral 1,2-azido ethanols with PPh3 in water/THF, and then converted into the Boc or acetamide derivatives.

Synthesis of a Bicyclic Azetidine with In Vivo Antimalarial Activity Enabled by Stereospecific, Directed C(sp3)–H Arylation

“…Indeed, BRD3914, an analog lacking substitution at C2, was found to retain substantial antimalarial activity in vitro (EC 50 = 13 nM, Dd2 strain). 6 …”

One Pot Asymmetric Synthesis of (R)‐Phenylglycinol from Racemic Styrene Oxide via Cascade Biocatalysis

“…The crude product was then purified by flash chromatography on a silica gel column to give ( R )‐phenylglycinol as a white solid in 81.9 % yield and 99 % ee . 1 H NMR (600 MHz, CDCl 3 ): δ 7.38–7.30 (m, 4H), 7.30–7.26 (m, 1H), 4.04 (dd, J=8.3, 4.3 Hz, 1H), 3.74 (dd, J=10.9, 4.3 Hz, 1H), 3.56 (dd, J=10.8, 8.3 Hz, 1H), 2.19 (br, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 142.77, 128.77, 127.65, 126.59, 68.11, 57.48.…”

“…The crude product was then purified by flash chromatography on a silica gel column to give (R)-phenylglycinol as a white solid in 81.9 % yield and 99 % ee. 1 H NMR (600 MHz, CDCl 3 ): [24] 77, 128.77, 127.65, 126.59, 68.11, 57.48.…”

DFT-Assisted Design and Evaluation of Bifunctional Amine/Pyridine-Oxazoline Metal Catalysts for Additions of Ketones to Unactivated Alkenes and Alkynes

“…The current styrene epoxide opening method using sodium azide and hot water has been shown to give clean inversion of stereochemistry. [31] Reduction of 8 using Pd/C under H2 afforded amino alcohol 9 in excellent yield. EDC peptide coupling with picolinic acid followed by oxazoline formation using Deoxo-Fluor ® [32] [33] proceeded smoothly to afford 11.…”