Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups

Abstract

Conjugate (or 1,4-) additions of carbanionic species to α,β-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several known chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates1. However, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that are able to incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic α,β,γ,δ-doubly unsaturated acceptors are unknown2. Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable, as the resulting products would be subjected to further modifications; such reactions, especially when dienoates contain two equally substituted olefins, are scarce3 and are confined to reactions promoted by a phosphine–copper (with alkyl Grignard4,5, dialkylzinc or trialkylaluminum compounds6,7), a diene–iridium (with arylboroxines)8,9, and a bisphosphine–cobalt catalyst (with monosilyl-acetylenes)10. 1,6-conjugate additions are otherwise limited to substrates where there is full substitution at C411. It is not clear why certain catalysts favor bond formation at C6, and – while there are a small number of catalytic enantioselective conjugate allyl additions12,13,14,15 – related 1,6-additions and processes involving a propargyl unit are non-existent. In this manuscript, we show that an easily accessible organocopper catalyst can promote 1,6-conjugate additions of propargyl and 2-boryl-substituted allyl groups to acyclic dienoates with high selectivity. A commercially available allenylboron compound or a monosubstituted allene may be used. Products can be obtained in up to 83 percent yield, >98 percent diastereo- (for allyl additions) and 99:1 enantiomeric ratio. Mechanistic details, including the origins of high site- (1,6- versus 1,4-) and enantioselectivity as a function of the catalyst structure and reaction type, have been elucidated by means of density functional theory (DFT) calculations.

Direct Formic Acid MediatedZ‐Selective Reductive Coupling of Dienes and Aldehydes

“…[6] Under these reaction conditions,p roducts derived from chainwalking isomerization are observed, [6b] restricting access to anarrow range of product classes. [7] Thelack of generality in Z-selective diene additions highlights the difficulty in controlling both site-and stereoselectivity in catalytic diene functionalization, [8] particularly in those reactions that generate thermodynamically less favorable product isomers. [9] From am echanistic perspective,i mproving reductive chemoselectivity while inhibiting chain-walking events in diene-aldehyde coupling can potentially be realized by tailoring the reactivity of the Rh intermediates involved in the reaction pathway.Specifically,ifboth diene insertion into the Rh-hydride catalyst and electrophilic capture of the resultant Rh-allyl outpace undesirable isomerization, bhydride elimination, or other reductive processes,adirect and selective coupling process should be possible.Werecently reported that formic acid acts as reducing agent for the Zselective 1,6-reduction of dienyl esters [10] and questioned whether this pathway could be diverted to enable reductive coupling.F ormic acid has been used as areductant for metalcatalyzed CÀCb ond-forming carbonyl allylation and vinylation processes.…”

Diastereoselective Hydrolysis of Branched Malonate Diesters by Porcine Liver Esterase: Synthesis of 5‐Benzyl‐Substituted Cα‐Methyl‐β‐proline and Catalytic Evaluation

“…Recently, Hoveyda et al reported a PLE‐mediated diastereoselective desymmetrization of a chiral malonate diester . To the best of our knowledge, there are no published reports of PLE‐catalyzed hydrolysis of malonate diesters with a preexisting chiral center and a phthalimide group.…”

An Economical, Sustainable Pathway to Indole-Containing Oxindoles: Iron-Catalyzed 1,6-Conjugate Addition in Glycerol

“…All the reagents used were of analytical grade without further purification. Oxoindole-derived methide derivatives was obtained following the literature [12].…”

“…In this regard, the 1,6-conjugated addition reaction catalyzed by Brønsted acids or Lewis acids for new chemical bond formation can provide a variety of bioactive compounds, and has complete atom economy [11]. Thus, the 1,6-conjugated addition reaction is attracting much research interest in academia [12][13][14].…”