Preparation of Stereodefined Homoallylic Amines from the Reductive Cross-Coupling of Allylic Alcohols with Imines

• Published in: Journal of organic chemistry Vol. 75; no. 23; pp. 8048 - 8059
• Main Authors: Chen, Ming Z, McLaughlin, Martin, Takahashi, Masayuki, Tarselli, Michael A, Yang, Dexi, Umemura, Shuhei, Micalizio, Glenn C
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.12.2010; Amer Chemical Soc
• Subjects: Aliphatic compounds; Alkenes - chemistry; Amines - chemical synthesis; Amines - chemistry; Chemistry; Chemistry, Organic; Cross-Linking Reagents - chemistry; Exact sciences and technology; Imines - chemistry; Kinetics and mechanisms; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Propanols - chemistry; Reactivity and mechanisms; Science & Technology; Stereoisomerism; METAL-PROMOTED CYCLIZATION; ALKENES; ASYMMETRIC-SYNTHESIS; SPECTROSCOPIC PROPERTIES; MEDIATED SYNTHESIS; ENANTIOSELECTIVE ALLYLATION; ALKYNES; IN-SITU GENERATION; ZIRCONOCENE COMPLEXES; GRIGNARD-REAGENTS; Enantioselectivity; Molecular structure; Titanium complex; Haloarene; Alcohol; Chiral compound; Selectivity; Stereochemistry; Allylic compound; Organic sulfide; Chemical reduction; Stereoselectivity; Alkene; Amine; Asymmetric synthesis; Vinylic compound; Cross reaction; Reaction mechanism; Alkoxide; Aromatic compound; Metalation; Chemical synthesis; Heterocyclic compound; Halogen Organic compounds; Chemical reagent; Regioselectivity; Aliphatic compound; Chemical bond; Organometallic compound; Organic silane; Imine; Empirical model; Diastereoselectivity; Chemical coupling; Transition state; Fluorine Organic compounds; Homoallylic compound; Ethylenic compound
• DOI: 10.1021/jo101535d
• ISSN: 0022-3263

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.