Nickel-Catalyzed Regio- and Enantioselective Hydroalkenylation of Aldehydes with 2-Azadienes
Ya Du1, Lening Zhang1, Shengzu Duan1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products; School of Pharmacy, Yunnan University, Kunming 650500, P. R. China.
Abstract:
The development of new methods for the utilization of aldehydes has garnered much attention because their addition products, chiral alcohols, are common structural elements in the pharmaceutical industry. Despite significant progress in the catalytic asymmetric synthesis of secondary allylic alcohols, the synthesis of derivatives bearing amino functionalities remains challenging. Herein, we report a highly regio- and enantioselective nickel-catalyzed direct hydrovinylation of aldehydes with 2-azadienes, delivering a series of 2-azadiene-substituted alcohols in good yields (up to 96%) with high enantioselectivities (up to 99%) under mild conditions. These high-value γ-amino alcohols can be incorporated into natural products and bioactive molecules and are readily transformed into a variety of useful structural motifs.
Related Concept Videos
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
02:34Preparation of Alkynes: Dehydrohalogenation
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
01:22Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
02:36Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...