Direct Asymmetric Amination of α‑Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantio­selectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantio­enriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (<i>S</i>)-ketamine, the more active enantiomer of this versatile pharmaceutical

Gold(I)-Catalyzed Enantioselective Carboalkoxylation of Alkynes

A highly enantioselective carboalkoxylation of alkynes catalyzed by cationic (DTBM-MeO-Biphep)­gold­(I) complexes is reported. Various optically active β-alkoxyindanone derivatives were obtained in good yields with high enantioselectivities. Furthermore, this methodology was extended to the enantioselective synthesis of 3-methoxycyclopentenones. The reaction is proposed to proceed through an enantioselective cyclization of intermediates containing vinylgold­(I) and prochiral oxocarbenium moieties

Well-Defined Chiral Gold(III) Complex Catalyzed Direct Enantioconvergent Kinetic Resolution of 1,5-Enynes

The development of a gold­(III) catalyzed direct enantioconvergent 1,5-enyne cycloisomerization and kinetic resolution reaction is described. The transformation results in highly enantioenriched bicyclo[3.1.0]­hexenes at all levels of conversion, with no racemization or symmetrization taking place during the course of the reaction, and simultaneously affords optically enriched 1,5-enynes. This report marks the first highly enantioselective transformation catalyzed by a well-defined cationic gold­(III) catalyst and demonstrates the unique potential of gold­(III) complexes in enantioselective catalysis

Well-Defined Chiral Gold(III) Complex Catalyzed Direct Enantioconvergent Kinetic Resolution of 1,5-Enynes

The development of a gold­(III) catalyzed direct enantioconvergent 1,5-enyne cycloisomerization and kinetic resolution reaction is described. The transformation results in highly enantioenriched bicyclo[3.1.0]­hexenes at all levels of conversion, with no racemization or symmetrization taking place during the course of the reaction, and simultaneously affords optically enriched 1,5-enynes. This report marks the first highly enantioselective transformation catalyzed by a well-defined cationic gold­(III) catalyst and demonstrates the unique potential of gold­(III) complexes in enantioselective catalysis

Chiral Anion Phase-Transfer Catalysis Applied to the Direct Enantioselective Fluorinative Dearomatization of Phenols

Chiral anion phase-transfer catalysis has enabled the direct and highly enantioselective fluorinative dearomatization of phenols catalyzed by a BINOL-derived phosphate. The process efficiently transforms simple, readily available phenols into fluorinated chiral small molecules bearing reactive functionality under ambient reaction conditions with high enantioselectivity. The close relationship of the products with well-studied <i>o</i>-quinols provides numerous avenues for synthetic elaboration and exciting opportunities for bioisosteric replacement of hydroxyl with fluorine in natural products

Biomimetic Approach to the Catalytic Enantioselective Synthesis of Flavonoids

Herein is reported the direct asymmetric addition of phenol nucleophiles to benzopyrylium salts as a means to produce enantioenriched flavonoid-like compounds. This enantioselective C–C bond construction was achieved through a chiral anion phase-transfer strategy that mimics the proposed biosynthesis of this structurally diverse set of natural products. The utility of this methodology was demonstrated in enantioselective synthesis of a 2,8-dioxabicyclo[3.3.1]­nonane and a 2,4-diarylbenzopyran

Biomimetic Approach to the Catalytic Enantioselective Synthesis of Flavonoids

Herein is reported the direct asymmetric addition of phenol nucleophiles to benzopyrylium salts as a means to produce enantioenriched flavonoid-like compounds. This enantioselective C–C bond construction was achieved through a chiral anion phase-transfer strategy that mimics the proposed biosynthesis of this structurally diverse set of natural products. The utility of this methodology was demonstrated in enantioselective synthesis of a 2,8-dioxabicyclo[3.3.1]­nonane and a 2,4-diarylbenzopyran

Gold(I)-Catalyzed Dearomative Rautenstrauch Rearrangement: Enantioselective Access to Cyclopenta[<i>b</i>]indoles

A highly enantioselective dearomative Rautenstrauch rearrangement catalyzed by cationic (<i>S</i>)-DTBM-Segphosgold­(I) is reported. This reaction provides a straightforward method to prepare enantioenriched cyclopenta­[<i>b</i>]­indoles. These studies show vast difference in enantioselectivity in the reactions of propargyl acetates and propargyl acetals in the chiral ligand-controlled Rautenstrauch reaction

Asymmetric Fluorination of α‑Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids

We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of this approach with the direct asymmetric fluorination of α-substituted cyclohexanones to generate quaternary fluorine-containing stereocenters. With these two chiral catalytic cycles operating together in a matched sense, high enantioselectivites can be achieved, and we envisage that this dual catalysis method has the potential to be more broadly applicable, given the breadth of enamine catalysis. It also represents a rare example of chiral enamine catalysis operating successfully on α-branched ketones, substrates commonly inert to this activation mode

An <i>In Situ</i> Directing Group Strategy for Chiral Anion Phase-Transfer Fluorination of Allylic Alcohols

An enantio­selective fluorination of allylic alcohols under chiral anion phase-transfer conditions is reported. The <i>in situ</i> generation of a directing group proved crucial for achieving effective enantio­control. In the presence of such a directing group, a range of acyclic substrates underwent fluorination to afford highly enantio­enriched α-fluoro homoallylic alcohols. Mechanistic studies suggest that this transformation proceeds through a concerted enantio­determining transition state involving both C–F bond formation and C–H bond cleavage