Enantioselective Allylic Alkylation Catalyzed by Novel C2‐Symmetric Bisphosphinites

In this article, we present our results concerning new C₂‐symmetric bisphosphinites with a (1R,2R)‐1,2‐bis([1,1′: 3′,1″‐terphenyl]‐5′‐yl)ethane backbone. For the given chirality of the backbone, derivatives with aromatic and aliphatic substituents at the donor P‐atoms were synthesized with moderate yields in a straightforward manner. These compounds were evaluated in the Pd⁰‐catalyzed enantioselective allylic alkylations (up to 67% ee).     

Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Alkyne Oxidation/Cyclopropanation of 1,6‐Enynes

A highly enantioselective oxidative cyclopropanation of 1,6‐enynes catalyzed by cationic Au^I/chiral phophoramidite complexes is presented. The new method provides convenient access to densely functionalized bicyclo[3.1.0]hexanes bearing three contiguous quaternary and tertiary stereogenic centers with high enantioselectivity (up to e.r. 98:2). Control experiments suggest that the quinoline moiety of the β‐gold vinyloxyquinolinium intermediate in the reaction plays an important role in promoting good enantioselectivity through a transitional auxiliary effect in the transition state.     

Z‐Selective Copper(I)‐Catalyzed Alkyne Semihydrogenation with Tethered Cu–Alkoxide Complexes

A highly stereoselective alkyne semihydrogenation with copper(I) complexes is reported. Copper–N‐heterocyclic carbene complex catalysts, bearing an intramolecular Cu?O bond, allow for the direct transfer of both hydrogen atoms from dihydrogen to the alkyne. The corresponding alkenes can be isolated with high Z selectivity and negligible overreduction to the alkane.     

Copper(I)‐Catalyzed Enantioselective Substitution of Allyl Chlorides with Diorganozinc Compounds

Ferrocenylamines are excellent catalysts for the enantioselective substitution of unsymmetrical allyl chlorides with dialkylzinc compounds in the presence of a copper(I ) salt. For example, in the reaction shown in Equation (1), the product is formed with 87 % ee and a S_N2′:S_N2 ratio of 97:3.     

C3‐Symmetric Trisimidazoline‐Catalyzed Enantioselective Bromolactonization of Internal Alkenoic Acids

A method for conducting enantioselective bromolactonization reactions of trisubstituted alkenoic acids, using the C₃‐symmetric trisimidazoline 1 and 1,3‐dibromo‐5,5‐dimethyl hydantoin as a bromine source, has been developed. The process generates chiral δ‐lactones that contain a quaternary carbon. The results of studies probing geometrically different olefins show that (Z)‐olefins rather than (E)‐olefins are favorable substrates for the process. The method is not only applicable to acyclic olefin reactants but can also be employed to transform cyclic trisubstituted olefins into chiral spirocyclic lactones. Finally, the synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide, an antifungal marine natural product.     

Copper‐Catalyzed Enantioselective Markovnikov Protoboration of α‐Olefins Enabled by a Buttressed N‐Heterocyclic Carbene Ligand

Reported is a highly enantioselective copper‐catalyzed Markovnikov protoboration of unactivated terminal alkenes. A variety of simple and abundant feedstock α‐olefins bearing a diverse array of functional groups and heterocyclic substituents can be used as substrates, and the reaction proceeds under mild reaction conditions at ambient temperature to provide expedient access to enantioenriched alkylboronic esters in good regioselectivity and with excellent enantiocontrol. Critical to the success of the protocol was the development and application of a novel, sterically hindered N‐heterocyclic carbene, (R,R,R,R)‐ANIPE, as the ligand for copper.     

Enantioselective Copper(I)‐Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters

An enantioselective, copper(I)‐catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl‐substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals into high‐value enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes.     

Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

The enantioselective intermolecular C2‐allylation of 3‐substituted indoles is reported for the first time. This directing group‐free approach relies on a chiral Ir‐(P, olefin) complex and Mg(ClO₄)₂ Lewis acid catalyst system to promote allylic substitution, providing the C2‐allylated products in typically high yields (40–99 %) and enantioselectivities (83–99 % ee) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2‐allylation, rather than C3‐allylation followed by in situ migration. Steric congestion at the indole‐C3 position and improved π–π stacking interactions have been identified as major contributors to the C2‐selectivity.