Cu‐Catalyzed Chemoselective Preparation of 2‐(Pinacolato)boron‐Substituted Allylcopper Complexes and their In Situ Site‐, Diastereo‐, and Enantioselective Additions to Aldehydes and Ketones

Meng, Fanke; Jang, Hwanjong; Jung, Byunghyuck; Hoveyda, Amir H.

doi:10.1002/anie.201301018

Cited by 201 publications

(83 citation statements)

References 35 publications

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“…With arylsubstituted allylic phosphates, reactions proceeded to >98% conversion with 2.75 mol % NHC−Ag complex 10b, 5.0 mol % CuCl 2 , and 1.5 equiv of propargyl−B(pin) reagent 1a. Enantioselective additions were complete within 6 h at ambient temperature, 22 and the desired products were isolated in ≥75% yield ( Table 2; >98% conversion throughout). Even in cases where the substrate carries a sizable aryl unit (cf.…”

Section: ■ Introduction and Backgroundmentioning

confidence: 99%

N-Heterocyclic Carbene–Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

et al. 2015

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The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.

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Section: ■ Introduction and Backgroundmentioning

confidence: 99%

N-Heterocyclic Carbene–Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

et al. 2015

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“…In our previous studies involving Cu–B(pin) additions to monosubstituted allenes in the presence of aldehydes and ketones, 8 a chiral phosphine proved to be most effective (vs nonselective chiral NHCs). Accordingly, we first examined the representative protoboration process under the same parameters.…”

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Catalytic Enantioselective Protoboration of Disubstituted Allenes. Access to Alkenylboron Compounds in High Enantiomeric Purity

2014

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Proto-boryl additions to 1,1-disubstituted allenes in the presence of 1.0–5.0 mol % of chiral NHC–Cu complexes, B2(pin)2, and t-BuOH proceed to afford alkenyl–B(pin) products in up to 98% yield, >98:2 site selectivity, and 98:2 er. The enantiomerically enriched alkenylboron products can be converted to otherwise difficult-to-access alkenyl bromides, methyl ketones or carboxylic acids. What’s more, the corresponding boronic acids may be used in highly stereoselective NHC−Cu-catalyzed allylic substitution reactions.

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“…Additionally, Hoveyda has developed exceptional copper-catalyzed borylative processes for the addition of olefin-derived nucleophiles bearing a boryl moiety to carbonyls. This chemistry has been highly successful in the enantioselective preparation of secondary alcohols from aldehydes (15, 16), although ketones represent more challenging substrates for this enantioselective process (16). Alkenes and ketones constitute two of the most widely available building blocks for organic synthesis.…”

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Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

Yang

Perry

Lü

et al. 2016

Science

254

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Enantioenriched alcohols found in an array of bioactive natural products and pharmaceutical agents are often synthesized by asymmetric nucleophilic addition to carbonyls. However, this approach generally shows limited functional group compatibility, requiring the use of preformed organometallic reagents in conjunction with a stoichiometric or sub-stoichiometric amount of chiral controller to deliver optically active alcohols. Herein we report a copper-catalyzed strategy for the stereoselective nucleophilic addition of propargylic and other alkyl groups to ketones using easily accessible (poly)unsaturated hydrocarbons as latent carbanion equivalents. Our method features the catalytic generation of highly enantioenriched organocopper intermediates and their subsequent diastereoselective addition to ketones, allowing for the effective construction of highly substituted stereochemical dyads with excellent stereocontrol. Moreover, this process is general, scalable, and occurs at ambient temperature.

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Cu‐Catalyzed Chemoselective Preparation of 2‐(Pinacolato)boron‐Substituted Allylcopper Complexes and their In Situ Site‐, Diastereo‐, and Enantioselective Additions to Aldehydes and Ketones

Cited by 201 publications

References 35 publications

N-Heterocyclic Carbene–Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

N-Heterocyclic Carbene–Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

Catalytic Enantioselective Protoboration of Disubstituted Allenes. Access to Alkenylboron Compounds in High Enantiomeric Purity

Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

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