Enantioselective One‐Pot Catalytic Synthesis of 4,5‐Epoxy‐3‐alkanols and 1‐Phenyl‐2,3‐epoxy‐1‐alkanols from α,β‐Unsaturated Aldehydes

Abstract

Conformationally restricted perhydrobenzoxazines have been demonstrated to be good chiral ligands for one‐pot asymmetric ethylation/epoxidation, and the unprecedented arylation/epoxidation of trisubstituted α,β‐unsaturated aldehydes. The scope of the reaction has been studied and a wide set of substrates with allylic strain of different nature has been explored, obtaining good or total diastereoselectivities in all cases. The enantiocontrol was good or high for the ethylation/epoxidation reaction, whereas it remained at moderate or good levels for the arylation/epoxidation. The reaction is general for trisubstituted enals, and alkylic and aromatic substituents are tolerated at both the α‐ and β‐position of the unsaturated aldehyde; however, disubstituted enals remain challenging substrates. When the one‐pot and two‐pot protocols were compared, no significant differences concerning the stereocontrol were found, so the advantages of the one‐pot procedure are clear.

Stereodivergent Access to Enantioenriched Epoxy Alcohols with Three Stereogenic Centers via Ruthenium-Catalyzed Transfer Hydrogenation

“…As shown in Scheme a, epoxidation of stoichiometric chiral allylic alcohols and reduction of chiral epoxy ketones are commonly used methods to produce the target EEAs, but the limited commercial availabilities of these chiral reagents prevent the wide utility of such a strategy, and in some cases, the diastereoselectivities of the reaction are hard to control . Asymmetric catalytic approaches are more attractive to achieve the synthesis of EEAs with three stereocenters, but it is relatively surprising that to date extremely fewer one-step asymmetric catalytic methods have been developed to achieve this purpose, and in most cases multiple steps are needed, which result in relatively lower atom economy and higher cost . A selected four-step asymmetric catalytic synthesis route is shown in Scheme b .…”

Nazarov cyclization of divinyl ketones bearing an ester group at the β-position: a remarkable effect of α-substitution and alkene geometry on regioselectivity

“…Step-1: 16 Yield: 83%; colorless oil; R f = 0.3 (15% EtOAc/hexanes); 1 H NMR (500 MHz, 1,130.0,129.9,129.4,127.5,113.9,74.5,55.2,30.1,9.7;IR (neat):  max 3448,2923,2842,1602,1506,1246,1173,1032,940,824 8,161.3,141.9,129.8,127.1,123.7,114.2,55.2,33.7,8.2;IR (neat):  max 2932,2843,1655,1594,1507,1250,1174,1116,1029,981,826…”