An Enantioselective Entry to Substituted 6-Membered Nitrogen Heterocycles from Chiral Pyridinium Salts via Selective Epoxidation of Tetrahydropyridine Intermediates

Abstract

Epoxidation reactions of chiral 2-and 2,6-substituted 1,2,5,6-tetrahydropyridines 6, 11, 12 and 21 proceed with good to high stereoselectivity and excellent yields using pertrifluoroacetic acid as reagent. Epoxides such as 15, 16 and 19 are unstable but they can be deprotonated by LDA to give allylic alcohols such as 28, 30 or 32. These alcohols turned out to be potentially useful synthons, whose further oxidation or conversion to enones (29, 31) allows, in principle, introduction of a number of substituents on the piperidine ring. In particular, this is exemplified by a five-steps synthesis, from chiral tetrahydropyridine 6, of tetrasubstituted piperidine 7 in 26% overall yield.

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

“…However, the reaction was almost nonselective regardless to the reaction temperature, affording a mixture of both syn and anti isomers of epoxide 5 in comparable amounts ( syn / anti , 58:42; see Supporting Information File 1 , page S25). Although the syn selectivity was further improved (80:20) by using the in situ-generated trifluoroperoxyacetic acid [ 28 ], the reaction suffered from formation of a high level of impurities. Gratifyingly, this issue has been overcome by the use of hydrogen peroxide in the presence of phosphotungstic heteropoly acid, a commercial heteropoly acid [ 29 – 30 ].…”

First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases

“…We decided to avoid the use of mCPBA as epoxidation agent because of its known ability to assist allylic alcohol epoxidation; [21] in a single assay, we obtained a 1:1 mixture of epoxides endo-and exo-15 after subsequent benzylation. We therefore set out to carry out the epoxidation reaction with DMDO, which could not form any intermolecular hydrogen bond with the hydroxy group.…”

Ammonium directed dihydroxylation of N,N-dibenzylaminocyclohex-2-ene: metal-free syntheses of the diastereoisomers of 3-dibenzylamino-1,2-dihydroxycyclohexane

“…11 We communicate herein an ammonium directed, metal-free dihydroxylation protocol of allylamines that has been applied to the preparation of all the diastereoisomers of 3-dibenzylamino-1,2-dihydroxycyclohexane. 12,13 Our strategy in this area centred upon protection of the amine by protonation prior to oxidation, with ammonium ion formation proposed to negate N-oxidation upon treatment with an oxidising agent. This ammonium ion would simultaneously provide a hydrogen bond donor capable of directing the subsequent epoxidation, the epoxide from which would be capable of regioand stereoselective ring opening with a suitable nucleophile.…”