Catalytic Enantioselective Conjugate Additions of (pin)B‐Substituted Allylcopper Compounds Generated in situ from Butadiene or Isoprene

Abstract

Multicomponent catalytic enantioselective transformations that entail the combination of butadiene or isoprene (common feedstock), an enoate (prepared in one step) and B 2 (pin) 2 (commercially available) are presented. These processes constitute an uncommon instance of conjugate addition of an allyl moiety and afford the desired products in up to 83% yield and 98:2 enantiomeric ratio. Based on DFT calculations stereochemical models and rationale for the observed profiles in selectivity are provided. Keywordsboron; conjugate additions; copper; enantioselective catalysis; synthesis Multicomponent catalytic transformations can convert readily accessible starting materials to substantially more complex molecules. [1] One desirable scenario would involve 1,3-dienes and especially butadiene, a common feedstock produced in more than 10 million tons per year worldwide. However, catalytic enantioselective reactions with these unsaturated hydrocarbons, the majority of which are cycloadditions, are limited in number. [2] There are only the seminal contributions of Krische [3] regarding coupling of butadiene with alcohols or aldehydes, and the disclosures on reactions of 1-substituted butadienes with aldehydes [4a] and combination of aryl-based reagents and sodium dimethylmalonate. [4b-c] Enantioselective processes have been recently developed that begin with the addition of a chiral Cu-B(pin) complex (pin = pinacolato) to an alkene, [5] affording organocopper species that may then react with another electrophile. Cu-based catalysts have accordingly been utilized to merge an allene and an aldehyde or ketone, [6] an allene and an allylic phosphate, [7] or an enyne and an aldehyde enantioselectively. [8] Related strategies, some with a Pd-based co-catalyst, entail the use of an aryl olefin and an aryl or benzyl halide (nonenantioselective) [9] or an allylic carbonate (enantioselective). [10] A catalytic process with butadiene, B 2 (pin) 2 and an enoate (Scheme 1) might be envisioned that constitutes enantioselective conjugate addition (ECA) of an allyl group, a class of Correspondence to: Amir H. Hoveyda. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript valuable reactions that remains severely underdeveloped. [11] Further, the only reported multicomponent enantioselective conjugate additions [12] begin with initial addition to an alkynyl or alkenyl group followed by an intramolecular conjugate addition. [13] The envisioned sequence would commence with the conversion of a 1,3-diene to allylcopper species ii and iii [14] and then iv or v (α-vs. γ-addition). One possible complication would be competitive boryl conjugate addition (i → vi, Scheme 1). [15 ] This is a more formidable chemoselectivity challenge compared to when an allenyl, [6,7,13b] an alkynyl [13a] or a styrenyl [13] substrate is used because these latter species are either less hindered and/or more electrophilic (vs. a butadiene).Preliminary experiments with butadiene and phosphine or N-heterocyclic carbe...

Nickel‐Catalyzed Regioselective Arylboration of Conjugated Dienes

“…The carboboration of 1,3‐dienes with the one‐step addition of carbon‐ and boron‐based groups greatly increases the complexity of the products that can be obtained as well as the efficiency of the synthesis [3] . However, it is challenging to perform such reactions with both regioselectivity and stereoselectivity at the double bonds (Figure 1a) [4] . Currently, such syntheses are primarily performed on the basis of copper catalysis [3a] .…”

“…[3] However, it is challenging to perform such reactions with both regioselectivity and stereoselectivity at the double bonds ( Figure 1a). [4] Currently, such syntheses are primarily performed on the basis of copper catalysis. [3a] As an example, the Oestreich group demonstrated the use of ketone electrophiles to quench copper-based intermediates, [5] while Cao and Liao demonstrated the reactions of imine electrophiles to generate homoallylic amines.…”