Copper‐Catalyzed Enantioselective β‐Boration of Acyclic Enones

Josi or Mandy? Asymmetric conjugate addition of diboron to acyclic enones catalyzed by copper affords chiral organoboronates that possess a boronate group at the β stereocenter with excellent chemical yields and enantioselectivities (see scheme). This method accommodates the structural variation of acyclic enones and provides access to highly functionalized chiral organoboronates in one step.

     

Copper‐Catalyzed Enantioselective 1,6‐Boration of para‐Quinone Methides and Efficient Transformation of gem‐Diarylmethine Boronates to Triarylmethanes

Presented is the first enantioselective copper‐catalyzed 1,6‐conjugate addition of bis(pinacolato)diboron to para‐quinone methides. The reaction proceeds with excellent yields and good to excellent enantioselectivities, and provides an attractive approach to the construction of optically active gem‐diarylmehtine boronic esters. Additionally, the subsequent conversion of the derived potassium trifluoroborates into triarylmethanes with highly enantiospecificity was realized.     

Tertiary α‐Silyl Alcohols by Diastereoselective Coupling of 1,3‐Dienes and Acylsilanes Initiated by Enantioselective Copper‐Catalyzed Borylation

An efficient synthesis of functionalized tertiary α‐silyl alcohols by an enantio‐ and diastereoselective copper‐catalyzed three‐component coupling of 1,3‐dienes, bis(pinacolato)diboron, and acylsilanes is reported. The reaction proceeds well with different 1,3‐dienes and a broad range of aryl‐ as well as alkenyl‐ but also alkyl‐substituted acylsilanes. The target compounds are formed with high regio‐, diastereo‐, and enantioselectivity (up to 99 % ee and d.r. >20:1) and are highly versatile synthetic building blocks.     

Enantioselective Copper‐Catalyzed Carboetherification of Unactivated Alkenes

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper‐catalyzed cyclization of γ‐unsaturated pentenols which terminates in C? C bond formation, a net alkene carboetherification. Both intra‐ and intermolecular C? C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused‐ring and bridged‐ring oxabicyclic products. Transition‐state calculations support a cis‐oxycupration stereochemistry‐determining step.     

Enantioselective Synthesis of Cyclobutylboronates via a Copper‐Catalyzed Desymmetrization Approach

The first catalytic enantioselective synthesis of cyclobutylboronates, by using a chiral copper(I) complex, is reported. A broad variety of cyclobutanes have been prepared with consistently high levels of diastereo‐ and enantiocontrol. Moreover, this method constitutes the first report of an enantioselective desymmetrization of meso‐cyclobutenes to prepare chiral cyclobutanes.     

Construction of Quaternary Stereogenic Carbon Centers through Copper‐Catalyzed Enantioselective Allylic Cross‐Coupling with Alkylboranes

A combination of an in situ generated chiral Cu^I/DTBM‐MeO‐BIPHEP catalyst system and EtOK enabled the enantioselective S_N2′‐type allylic cross‐coupling between alkylborane reagents and γ,γ‐disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp³‐alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross‐coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.     

Regio‐ and Enantioselective Synthesis of N‐Allylindoles by Iridium‐Catalyzed Allylic Amination/Transition‐Metal‐Catalyzed Cyclization Reactions

Regio‐ and enantioselective synthesis of N‐allylindoles was realized through an iridium‐catalyzed asymmetric allylic amination reaction with 2‐alkynylanilines and subsequent transition‐metal‐catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir‐catalysis were treated with catalytic amount of NaAuCl₄ ? 2 H₂O or PdCl₂ providing various substituted N‐allylindoles in excellent yields and enantioselectivities.     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Highly Enantioselective Copper‐Catalyzed Ring Opening of Oxabicyclic Alkenes with Grignard Reagents

A highly efficient copper‐catalyzed enantioselective ring opening of oxabicylic alkenes with Grignard reagents has been developed by using chiral spiro phosphine ligands. Excellent trans selectivities, good yields, and high enantioselectivities are obtained for a broad range of Grignard reagents under mild reaction conditions. The catalyst system shows an extraordinary activity and the TON of the reaction reaches 9000.     

Construction of Quaternary Stereogenic Carbon Centers through Copper‐Catalyzed Enantioselective Allylic Alkylation of Azoles

Copper‐catalyzed enantioselective allylic alkylation of azoles with γ,γ‐disubstituted primary allylic phosphates was achieved using a new chiral N‐heterocyclic carbene ligand bearing a naphtholic hydroxy group. This reaction occurred with excellent branch regioselectivity and high enantioselectivity, thus forming a controlled all‐carbon quaternary stereogenic center at the position α to the heteroaromatic ring.     

Synthesis of Branched Alkylboronates by Copper‐Catalyzed Allylic Substitution Reactions of Allylic Chlorides with 1,1‐Diborylalkanes

Reported herein is a copper‐catalyzed S_N2′‐selective allylic substitution reaction using readily accessible allylic chlorides and 1,1‐diborylalkanes, a reaction which proceeds with chemoselective C?B bond activation of the 1,1‐diborylalkanes. In the presence of a catalytic amount of [Cu(IMes)Cl] [IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazole‐2‐ylidene] and LiOtBu as a base, a range of primary and secondary allylic chlorides undergo the S_N2′‐selective allylic substitution reaction to produce branched alkylboronates. The synthetic utilities of the obtained alkylboronates are also presented.     

Enantioselective Rhodium‐Catalyzed Cycloisomerization of (E)‐1,6‐Enynes

An enantioselective rhodium(I)‐catalyzed cycloisomerization reaction of challenging (E)‐1,6‐enynes is reported. This novel process enables (E)‐1,6‐enynes with a wide range of functionalities, including nitrogen‐, oxygen‐, and carbon‐tethered (E)‐1,6‐enynes, to undergo cycloisomerization with excellent enantioselectivity, in a high‐yielding and operationally simple manner. Moreover, this Rh^I‐diphosphane catalytic system also exhibited superior reactivity and enantioselectivity for (Z)‐1,6‐enynes. A rationale for the striking reactivity difference between (E)‐ and (Z)‐1,6‐enynes using Rh^I‐BINAP and Rh^I‐TangPhos is outlined using DFT studies to provide the necessary insight for the design of new catalyst systems and the application to synthesis.     

Enantioselective Synthesis of All‐Carbon Quaternary Stereogenic Centers via Copper‐Catalyzed Asymmetric Allylic Alkylation of (Z)‐Allyl Bromides with Organolithium Reagents

A copper/phosphoramidite catalyzed asymmetric allylic alkylation of Z trisubstituted allyl bromides with organolithium reagents is reported. The reaction affords all‐carbon quaternary stereogenic centers in high yields and very good regio‐ and enantioselectivity. This systematic study illustrates the crucial role of the olefin geometry of the allyl substrate on the outcome of the reaction and provides a viable alternative to access these important structural motifs.     

Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

The first highly diastereo‐ and enantioselective synthesis of five‐membered spiro‐2H‐pyrroles was achieved using an Ir‐catalyzed asymmetric allylic dearomatization reaction. The spiro‐2H‐pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir‐complex K1 , derived from [Ir(cod)Cl]₂ (cod=1,5‐cyclooctadiene) and N‐benzhydryl‐N‐phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo‐ and enantioselectivities.     

Copper‐Catalyzed Enantioselective Allylic Alkylation with a γ‐Butyrolactone‐Derived Silyl Ketene Acetal

Herein, we report a Cu‐catalyzed enantioselective allylic alkylation using a γ‐butyrolactone‐derived silyl ketene acetal. Critical to the development of this work was the identification of a novel mono‐picolinamide ligand with the appropriate steric and electronic properties to afford the desired products in high yield (up to 96 %) and high ee (up to 95 %). Aryl, aliphatic, and unsubstituted allylic chlorides bearing a broad range of functionality are well‐tolerated. Spectroscopic studies reveal that a Cu^I species is likely the active catalyst, and DFT calculations suggest ligand sterics play an important role in determining Cu coordination and thus catalyst geometry.