Preparation of stereodefined homoallylic amines from the reductive cross-coupling of allylic alcohols with imines.
Ming Z. Chen,Martin McLaughlin,Masayuki Takahashi,Michael A. Tarselli,Dexi Yang,Shuhei Umemura,Glenn C. Micalizio +6 more
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TLDR
Empirical models are proposed that are consistent with the observed stereochemical course of these coupling reactions en route to chiral homoallylic amines possessing di- or trisubstituted alkenes and anti- or syn- relative stereochemistry at the allylic and homoALLYlic positions.Abstract:
Regio-, diastereo-, and enantioselective coupling reactions between imines and allylic alcohols have been developed. These coupling reactions deliver complex homoallylic amine products through a convergent C-C bond forming process that does not proceed through intermediate allylic organometallic reagents. In general, convergent coupling, by exposure of an allylic alkoxide to a preformed Ti-imine complex, occurs with allylic transposition in a predictable and stereocontrolled manner. While simple diastereoselection in these reactions is high, delivering anti-products with ≥20:1 selectivity, the organometallic transformation described is compatible with a diverse range of functionality and substrates (including aliphatic and aromatic imines, allylic silanes, trisubstituted alkenes, vinyl- and aryl halides, trifluoromethyl groups, thioethers, and aromatic heterocycles). Alkene geometry of the products is a complex function of the allylic alcohol structure and is consistent with a mechanistic proposal based on syn-carbometalation followed by syn-elimination by way of a boat-like transition state geometry. Single asymmetric coupling reactions provide a means to translate the stereochemical information of the allylic alcohol to the homoallylic amine or to control diastereoselection in the coupling reactions of achiral allylic alcohols with chiral imines. Double asymmetric coupling reactions are also described that afford a unique means to control stereoselection in these complex convergent coupling processes. Finally, empirical models are proposed that are consistent with the observed stereochemical course of these coupling reactions en route to chiral homoallylic amines possessing di- or trisubstituted alkenes and anti- or syn- relative stereochemistry at the allylic and homoallylic positions.read more
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Diastereoselective allylation of carbonyl compounds and imines: application to the synthesis of natural products.
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Enantioselective Heck Arylations of Acyclic Alkenyl Alcohols Using a Redox-Relay Strategy
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Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols.
Daniel L. Silverio,Sebastian Torker,Tatiana Pilyugina,Erika M. Vieira,Marc L. Snapper,Fredrik Haeffner,Amir H. Hoveyda +6 more
TL;DR: A set of small organic molecules that can catalyse reactions of unsaturated organoboron reagents with imines and carbonyls are introduced; the products of the reactions are enantiomerically pure amines and alcohols, which might serve as intermediates in the preparation of biologically active molecules.
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Modern applications of low-valent early transition metals in synthesis and catalysis
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Three-Component Coupling Sequence for the Regiospecific Synthesis of Substituted Pyridines
Ming Z. Chen,Glenn C. Micalizio +1 more
TL;DR: A de novo synthesis of substituted pyridines is described that proceeds through nucleophilic addition of a dithiane anion to an α,β-unsaturated carbonyl followed by metallacycle-mediated union of the resulting allylic alcohol with preformed trimethylsilane-imines.
References
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