Catalytic Asymmetric Synthesis of Piperidine Derivatives through the [4 + 2] Annulation of Imines with Allenes

Abstract

Although tertiary phosphines have emerged as remarkably versatile nucleophilic catalysts, there has been only very limited progress in achieving asymmetric catalysis with chiral phosphines. In this report, the first highly enantioselective variant of the Kwon annulation of imines with allenes is described. Thus, C2-symmetric chiral phosphepine 1 serves as an effective catalyst for this powerful process, furnishing an array of functionalized piperidine derivatives with very good stereoselectivity.

Synthesis of Chiral 2‐Phospha[3]ferrocenophanes and their Behaviour as Organocatalysts in [3+2] Cyclization Reactions

“…Since a number of synthetically useful processes have been highlighted, the development of asymmetric variants of phosphine-promoted transformations represents today a highly valuable challenge. Significant advances in this field have been reported mainly during the last decade: after the seminal work of Vedejs on enantioselective acylations, [3] several groups have investigated the use of chiral phosphines in Morita-Baylis-Hillman reactions, [4] [3 + 2] annulations of electron-poor unsaturated substrates (olefins, allenes and alkynes) with enones, unsaturated esters or imines, [5] [4 + 2] annulations with imines [6] and other miscellaneous reactions. [7] From these studies, only a few structural motifs have emerged as efficient scaffolds for phosphorus-based catalysts.…”

“…[5a] the binaphthyl-based phosphines 3 [9] and 4, [6] the a-amino acid-derived phosphine 5 [10] and the phosphinothiourea 6 [5d] have been highlighted as outstandingly efficient Lewis bases nucleophilic catalysts.…”

PHOSPHINE-CATALYZED [3 + 2] ANNULATION: SYNTHESIS OF ETHYL 5-(tert-BUTYL)-2-PHENYL-1-TOSYL-3-PYRROLINE-3-CARBOXYLATE

“…8 This broadly applicable reaction has since been applied to natural product synthesis 9 and has been developed into an asymmetric process. 10 The utility of the phosphine-catalyzed [4 + 2] annulation was further enhanced upon the successful application of activated alkenes to form functionalized cyclohexenes 11 and of trifluoromethyl ketones to form dihydropyrans. 12 Of particular importance to this discussion is the synthesis of 2,5-disubstituted pyrroline-3-carboxylates through the reactions of γ-substituted allenoates and imines.…”

Convenient Synthesis of Functionalized 6‐Styryl‐1,4,5,6‐tetrahydropyridines through a Domino [2+2+2] Cycloaddition Reaction

“…Even through a number of elegant synthetic methods have been applied for the preparation of the diverse functionalized tetrahydropyrdines, [7][8][9][10] the development of generally applicable and convenient protocols for these useful compounds is still an active research area in current synthetic and medicinal chemistry. [11][12][13] Among the various elegant synthetic methods, the reactions based on the diverse chemistry of imines have provided expedient practical protocols. The aza-Diels-Alder reaction that involves either aza-dienophiles or aza-dienes is one of the most versatile routes (Scheme 1, Equation 1).…”