Site- and Enantioselective Formation of Allene-Bearing Tertiary or Quaternary Carbon Stereogenic Centers through NHC–Cu-Catalyzed Allylic Substitution

Catalytic enantioselective allylic substitutions that result in addition of an allenyl group (<2% propargyl addition) and formation of tertiary or quaternary C–C bonds are described. Commercially available allenylboronic acid pinacol ester is used. Reactions are promoted by a 5.0–10 mol % loading of sulfonate-bearing chiral bidentate N-heterocyclic carbene (NHC) complexes of copper, which exhibit the unique ability to furnish chiral products arising from the S_N2′ mode of addition. Allenyl-containing products are generated in up to 95% yield, >98% S_N2′ selectivity, and 99:1 enantiomeric ratio (er). Site-selective NHC–Cu-catalyzed hydroboration of enantiomerically enriched allenes and conversion to the corresponding β-vinyl ketones demonstrates the method's utility

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

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 <i>t</i>-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

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

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 S_N2′/S_N2 (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 <i>Z</i>-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

NHC–Cu-Catalyzed Protoboration of Monosubstituted Allenes. Ligand-Controlled Site Selectivity, Application to Synthesis and Mechanism

Two types of NHC–Cu complexes catalyze protoborations of terminal allenes to afford valuable 1,1- or trisubstituted vinylboron species with high site selectivity and stereoselectivity. The scope of the method, application to natural product synthesis, and mechanistic basis for the observed selectivity trends are presented

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

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 S_N2′/S_N2 (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 <i>Z</i>-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

Defect Engineering into Metal–Organic Frameworks for the Rapid and Sequential Installation of Functionalities

Postsynthetic treatments are well-known and important functionalization tools of metal–organic frameworks (MOFs). Herein, we have developed a practical and rapid postsynthetic ligand exchange (PSE) strategy using a defect-controlled MOF. An increase in the number of defects amounts to MOFs with enhanced rates of ligand exchange in a shorter time frame. An almost quantitative exchange was achieved by using the most defective MOFs. This PSE strategy is a straightforward method to introduce a functionality into MOFs including bulky or catalytically relevant moieties. Furthermore, some mechanistic insights into PSE were revealed, allowing for a sequential ligand exchange and the development of multifunctional MOFs with controlled ligand ratios

Synthesis of α‑Borylmethyl‑(<i>E</i>)‑allylborons via Cu-Catalyzed Diboration of 1‑Substituted Allenols and Their Application in Stereoselective Aldehyde Allylation

1,2-Diborons with one boron atom each in the allyl and homoallyl positions are of great utility, especially as double-allylation reagents. However, only a few synthetic methods have been reported to date and have a limited substrate scope. Herein, we developed the Cu-catalyzed regio- and stereoselective synthesis of α-borylmethyl-(E)-allylborons from easily accessible 1-substituted allenols and bis(pinacolato)diboron. Importantly, this method allowed the highly efficient and regioselective formation of double-allylating diborons with diverse substituents, which would be otherwise cumbersome to synthesize, and could be successfully performed on a gram scale. The synthetic application of α-borylmethyl-(E)-allylborons was demonstrated by the enantio- and (Z)-selective allylation of aldehydes via Brønsted acid catalysis. Furthermore, (E)-allyl and (E)-homoallyl diols with excellent diastereoselectivity were generated by the Lewis acid catalyzed diastereo- and (E)-selective allyl transfer of (E)-allyldiborons to aldehydes. Using this strategy, the key intermediate in the construction of the C7–C12 fragment of (−)-discodermolide was also synthesized