Congested C–C Bonds by Pd-Catalyzed Enantioselective Allyl–Allyl Cross-Coupling, a Mechanism-Guided Solution

Ardolino, Michael J.; Morken, James P.

doi:10.1021/ja502280w

Cited by 118 publications

(51 citation statements)

References 78 publications

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“…1c) may interact with the C3–C4 π cloud, placing the nucleophilic Cγ near the dienoate C6. This pathway would be reminiscent of a 3,3′-reductive elimination proposed vis-à-vis enantioselective allyl–allyl coupling with Ni- and Pd complexes 17,18 . A similar reaction mode with an organocopper species has been mentioned in just one instance (again, without experimental or computational support) 19 .…”

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confidence: 99%

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

Meng

Torker

et al. 2016

Nature

127

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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.

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confidence: 99%

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

Meng

Torker

et al. 2016

Nature

127

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“…2 Recently, our group has disclosed a number of methods that employ chiral, small-bite-angle bidentate phosphine ligands to reverse the regioselectivity of these couplings to give branched 1,5-dienes of type C with excellent regio- and enantioselectivity (eq 2). 3 Recent mechanistic and computational studies 4 have supported previous proposals 3 that the reaction is operative through an inner-sphere 3,3′-reductive elimination 5 , in which coupling at carbons 3 and 3′ through the conformation as shown in B leads to the branched isomer. These studies are in line with computational studies on the preferred reductive elimination pathways for unsubstituted allylic systems by Eschavarren 5a and Espinet 5c , which also found the 3,3′-reductive elimination to be preferred over direct coupling at the 1 and 1′ carbons.…”

Section: Introductionmentioning

confidence: 67%

Branched/linear selectivity in palladium-catalyzed allyl-allyl cross-couplings: the role of ligands

Ardolino

Morken

2015

Tetrahedron

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While Pd-catalyzed allyl-allyl cross-couplings in the presence of small-bite-angle bidentate ligands reliably furnish the branched regioisomer with high levels of selectivity, cross-couplings in the presence of large-bite-angle bidentate ligands give varying, often unpredictable, levels of selectivity. In a combined computational and experimental study, we probe the underlying features that govern the regioselectivity in these metal-catalyzed cross-couplings.

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“…Unlike iridium and molybdenum catalysts, palladium has a natural propensity to form linear allylation products . However, it was reported that small‐bite‐angle ligands drive the allylpalladium equilibrium towards the formation of primary organopalladium species and this observation was cleverly used for the preparation of stereodefined vicinal tertiary and quaternary carbon stereogenic centers with BYPHEP L 3 as ligand (Scheme ) . Using substituted allylboronic esters and allyl chloride derivatives, the method proceeds with excellent regio‐ and enantiocontrol yet with a modest diastereoselectivity.…”

Section: Allylic Substitutionmentioning

confidence: 99%

Synthesis of Enantioenriched Vicinal Tertiary and Quaternary Carbon Stereogenic Centers within an Acyclic Chain

2019

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Overcoming the inherent difficulty to prepare quaternary carbon stereogenic centers, the diastereo‐ and enantioselective preparation of acyclic carbon backbones possessing vicinal quaternary and tertiary stereogenic centers (i.e. in a 1,2‐relationship) causes distorted geometries and represents a very acute problem in organic synthesis. Several approaches are discussed in this minireview underlining the challenges illustrated by the rather limited number of approaches available to practitioners.

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Congested C–C Bonds by Pd-Catalyzed Enantioselective Allyl–Allyl Cross-Coupling, a Mechanism-Guided Solution

Cited by 118 publications

References 78 publications

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

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

Branched/linear selectivity in palladium-catalyzed allyl-allyl cross-couplings: the role of ligands

Synthesis of Enantioenriched Vicinal Tertiary and Quaternary Carbon Stereogenic Centers within an Acyclic Chain

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