Rhodium(I)‐Catalyzed Bridged [5+2] Cycloaddition of cis‐Allene‐vinylcyclopropanes to Synthesize the Bicyclo[4.3.1]decane Skeleton

Previously reported was that cis‐ene‐vinylcyclopropanes (cis‐ene‐VCPs) underwent Rh‐catalyzed [5+2] reaction to give 5,7‐fused bicyclic products, where vinylcyclopropane (VCP) acts as five‐carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis‐ene‐VCPs to allene moiety, the corresponding cis‐allene‐VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7‐fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition. DFT calculations were applied to understand why this bridged [5+2] reaction is favored over the anticipated but not realized normal [5+2] reaction.     

Rhodium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic Dibenzosiloles by Enantioselective [2+2+2] Cycloaddition

A rhodium‐catalyzed asymmetric synthesis of silicon‐stereogenic dibenzosiloles has been developed through a [2+2+2] cycloaddition of silicon‐containing prochiral triynes with internal alkynes. High yields and enantioselectivities have been achieved by employing an axially chiral monophosphine ligand, and the present catalysis is also applicable to the asymmetric synthesis of a germanium‐stereogenic dibenzogermole. Preliminary studies on the optical properties of these compounds are also described.     

Rhodium(II)‐Catalyzed Cycloaddition Reactions of Non‐classical 1,5‐Dipoles for the Formation of Eight‐Membered Heterocycles

A new type of intermolecular rhodium(II)‐catalyzed [5+3] cycloaddition has been developed. This higher‐order cycloaddition between pyridinium zwitterion 1,5‐dipole equivalents and enol diazoacetates enables the formation of eight‐membered heterocyclic skeletons, which are otherwise difficult to construct. The optimized cycloaddition occurs efficiently under mild conditions with a wide range of pyridinium zwitterions and with high functional‐group tolerance.     

Phosphine‐Catalyzed Enantioselective Dearomative [3+2]‐Cycloaddition of 3‐Nitroindoles and 2‐Nitrobenzofurans

Over the past years, the metal‐catalyzed dearomative cycloaddition of 3‐nitroindoles and 2‐nitrobenzofurans have emerged as a powerful protocol to construct chiral fused heterocyclic rings. However, organocatalytic dearomative reaction of these two classes of heteroarenes has become a long‐standing challenging task. Herein, we report the first example of phosphine‐catalyzed asymmetric dearomative [3+2]‐cycloadditio of 3‐nitroindoles and 2‐nitrobenzofurans, which provide a new, facile, and efficient protocol for the synthesis of chiral 2,3‐fused cyclopentannulated indolines and dihydrobenzofurans by reacting with allenoates and MBH carbonates, respectively through a dearomative [3+2]‐cycloaddition.     

Total Synthesis of the Diterpenoid (+)‐Harringtonolide

Described herein is the first asymmetric total synthesis of (+)‐harringtonolide, a natural diterpenoid with an unusual tropone imbedded in a cagelike framework. The key transformations include an intramolecular Diels–Alder reaction and a rhodium‐complex‐catalyzed intramolecular [3+2] cycloaddition to install the tetracyclic core as well as a highly efficient tropone formation.     

Total Synthesis of (−)‐Merochlorin A

The first asymmetric total synthesis of the meroterpenoid (?)‐merochlorin A is described. The route features enantiospecific gold‐catalyzed tandem 1,3‐acyloxy migration/Nazarov/aldol reaction sequence to furnish the bicyclo[3.3.0]octane core in a single step from a linear propargylic 1,3‐enyne aldehyde. After completion of the central skeleton by reductive enol lactone rearrangement, late stage Diels–Alder cycloaddition/aromatization sequence installed the resorcinol. An additional salient feature of the synthesis is the assignment of the absolute configuration, which had not been determined previously.     

Base‐Free Conditions for Rhodium‐Catalyzed Asymmetric Arylation To Produce Stereochemically Labile α‐Aryl Ketones

The asymmetric arylation of 2,2‐dialkyl cyclopent‐4‐ene‐1,3‐diones with aryl boronic acids was found to be efficiently catalyzed by a chiral diene–rhodium μ‐chloro dimer, [{RhCl((R)‐diene*)}₂], in the absence of bases in toluene/H₂O to give 2,2‐dialkyl 4‐aryl cyclopentane‐1,3‐diones in high yields with high enantioselectivity. Such compounds can not be obtained with high enantiomeric purity under the standard basic conditions used for rhodium‐catalyzed asymmetric arylation because the α‐aryl ketone products undergo racemization under the basic conditions.     

Polymerization of conjugated 5‐[(5‐ethynyl‐1‐naphthyl)ethynyl]‐N,N‐dimethylnaphthalen‐1‐amine with rhodium and palladium complexes

The monomer 5‐[(5‐ethynyl‐1‐naphthyl)ethynyl]‐N,N‐dimethylnaphthalen‐1‐amine was satisfactory obtained through the heterocoupling reaction of 5‐ethynyl‐N,N‐dimethylnaphthalen‐1‐amine and 4‐(5‐iodo‐1‐naphthyl)‐2‐methyl‐3‐butyn‐2‐ol catalyzed by a palladium–copper system, followed by acetone elimination. Poly{5‐[(5‐ethynyl‐1‐naphthyl)ethynyl]‐N,N‐dimethylnaphthalen‐1‐amine} was obtained through the reaction of the acetylene monomer with homogeneous rhodium and palladium catalyst complexes. The structure of the polymers always showed a trans–cisoidal chain configuration on the basis of IR and NMR spectra. Moreover, only for the rhodium catalyst complex in methanol was a dimeric product isolated in a very low yield, having a conjugated terminal ene–yne structure, which permitted the consideration of a metallated chain‐transfer intermediate in the polymer propagation. The mass determination of the polymers, by osmometry and gel permeation chromatography techniques, showed low average molecular weights. The kinetics of the catalyzed polymerization were analyzed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2038–2047, 2007     

Aromatic Amide‐Derived Non‐Biaryl Atropisomers as Highly Efficient Ligands in Silver‐Catalyzed Asymmetric Cycloaddition Reactions

The synthesis of a series of aromatic amide‐derived non‐biaryl atropisomers with a phosphine group and multiple stereogenic centers is reported. The novel phosphine ligands exhibit high diastereo‐ and enantioselectivities (up to >99:1 d.r., 95–99 % ee) as well as yields in the silver‐catalyzed asymmetric [3+2] cycloaddition of aldiminoesters with nitroalkenes, which provides a highly enantioselective strategy for the synthesis of optically pure nitro‐substituted pyrrolidines. In addition, the experimental results with regard to the carbon stereogenic center as well as the amide stereochemistry confirmed the potential of hemilabile atropisomers as chiral ligand in catalytic asymmetric [3+2] cycloaddition reaction.     

Enantioselective total synthesis of (+)-asteriscanolide via Rh(I)-catalyzed [(5+2)+1] reaction

The total synthesis of (+)-asteriscanolide starting from two commercially available materials has been accomplished in 19 steps with a 3.8% overall yield. The key reaction is a chiral ene-vinylcyclopropane substrate induced Rh(I)-catalyzed [(5+2)+1] cycloaddition that efficiently constructs the [6.3.0] carbocyclic core with complete asymmetric induction.     

Nickel(0)‐Catalyzed Enantioselective Annulations of Alkynes and Arylenoates Enabled by a Chiral NHC Ligand: Efficient Access to Cyclopentenones

Cyclopentenones are versatile structural motifs of natural products as well as reactive synthetic intermediates. The nickel‐catalyzed reductive [3+2] cycloaddition of α,β‐unsaturated aromatic esters and alkynes constitutes an efficient method for their synthesis. Here, nickel(0) catalysts comprising a chiral bulky C₁‐symmetric N‐heterocyclic carbene ligand were shown to enable an efficient asymmetric synthesis of cyclopentenones from mesityl enoates and internal alkynes under mild conditions. The bulky NHC ligand provided the cyclopentenone products in very high enantioselectivity and led to a regioselective incorporation of unsymmetrically substituted alkynes.     

Asymmetric Synthesis of Protected Cyclohexenylamines and Cyclohexenols by Rhodium‐Catalyzed [2+2+2] Cycloaddition

It has been established that cationic rhodium(I)/axially chiral biaryl bis(phosphine) complexes catalyze the asymmetric [2+2+2] cycloaddition of 1,6‐enynes with electron‐rich functionalized alkenes, enamides, and vinyl carboxylates, to produce the corresponding protected cyclohexenylamines and cyclohexenols. Interestingly, regioselectivity depends on structures of substrates. The present cycloaddition was successfully applied to the enantioselective total synthesis of (?)‐porosadienone by using the amide moiety as a leaving group.     

On the Enantioselectivity of Transition Metal‐Catalyzed 1,3‐Cycloadditions of 2‐Diazocyclohexane‐1,3‐diones

The formal 1,3‐cycloaddition of 2‐diazocyclohexane‐1,3‐diones 1a –1 d to acyclic and cyclic enol ethers in the presence of Rh^II‐catalysts to afford dihydrofurans has been investigated. Reaction with a cis/trans mixture of 1‐ethoxyprop‐1‐ene ( 13a ) yielded the dihydrofuran 14a with a cis/trans ratio of 85 : 15, while that with (Z)‐1‐ethoxy‐3,3,3‐trifluoroprop‐1‐ene ( 13b ) gave the cis‐product 14b exclusively. The stereochemical outcome of the reaction is consistent with a concerted rather than stepwise mechanism for cycloaddition. The asymmetric cycloaddition of 2‐diazocyclohexane‐1,3‐dione ( 1a ) or 2‐diazodimedone (=2‐diazo‐5,5‐dimethylcyclohexane‐1,3‐dione; 1b ) to furan and dihydrofuran was investigated with a representative selection of chiral, nonracemic Rh^II catalysts, but no significant enantioselectivity was observed, and the reported enantioselective cycloadditions of these diazo compounds could not be reproduced. The absence of enantioselectivity in the cycloadditions of 2‐diazocyclohexane‐1,3‐diones is tentatively explained in terms of the Hammond postulate. The transition state for the cycloaddition occurs early on the reaction coordinate owing to the high reactivity of the intermediate metallocarbene. An early transition state is associated with low selectivity. In contrast, the transition state for transfer of stabilized metallocarbenes occurs later, and the reactions exhibit higher selectivity.     

RhII‐Catalyzed [3+2] Cycloaddition of 2 H‐Azirines with N‐Sulfonyl‐1,2,3‐Triazoles

Rh^II‐catalyzed intermolecular [3+2] cycloaddition of 2 H‐azirines with N‐sulfonyl‐1,2,3‐triazoles is disclosed, in which a series of fully functionalized pyrroles is produced via rhodium azavinyl carbene intermediates. A distinct feature of this reaction is that the azavinyl carbene serves as a [2 C] equivalent, instead of as [1 C] or aza‐[3 C] synthons, which have been reported previously in cyclopropanations and [3+n] cycloadditions. Moreover, this methodology has also been successfully applied in the total synthesis of URB447 as well as the formal synthesis of Atorvastatin (Lipitor).     

Tandem Insertion–[1,3]‐Rearrangement: Highly Enantioselective Construction of α‐Aminoketones

An enantioselective synthesis of α‐aminoketone derivatives were readily available through a tandem insertion–[1,3] O‐to‐C rearrangement reaction. The rhodium salt and chiral N,N′‐dioxide‐indium(III) complex make up relay catalysis, which enables the O?H insertion of benzylic alcohols to N‐sulfonyl‐1,2,3‐triazoles, and asymmetric [1,3]‐rearrangement of amino enol ether intermediates, subsequently. Preliminary mechanistic studies suggested that the [1,3] O‐to‐C rearrangement step proceeded through an ion pair pathway.     

ortho‐Oxygenative 1,2‐Difunctionalization of Diarylalkynes under Merged Gold/Organophotoredox Relay Catalysis

Reported herein is an ortho‐oxygenative 1,2‐difunctionalization of diarylalkynes under merged gold/organophotoredox catalysis to access highly functionalized 2‐(2‐hydroxyaryl)‐2‐alkoxy‐1‐arylethan‐1‐ones. Detailed mechanistic studies suggested a relay process, initiating with gold‐catalyzed hydroalkoxylation of alkynes, to generate enol‐ether followed by a key formal [4+2]‐cycloaddition reaction. The successful application of the present methodology was also shown for the synthesis of benzofurans.     

Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

The first asymmetric [3+1]‐cycloaddition was successfully achieved by copper(I) triflate/double‐sidearmed bisoxazoline complex catalyzed reactions of β‐triisopropylsilyl‐substituted enoldiazo compounds with sulfur ylides. This methodology delivered a series of chiral cyclobutenes in good yields with high enantio‐ and diastereoselectivities (up to 99 % ee , and >20:1 d.r.). Additionally, the [3+1]‐cycloaddition of catalytically generated metallo‐enolcarbenes was successfully extended to reaction with a stable benzylidene dichlororuthenium complex.     

Catalytic Enantioselective and Regioselective [3+3] Cycloadditions Using 2‐Indolylmethanols as 3 C Building Blocks

The first catalytic asymmetric cycloaddition using 2‐indolylmethanols as 3C building blocks has been established by a chiral phosphoric acid‐catalyzed enantioselective and regioselective [3+3] cycloaddition of 2‐indolylmethanols with azomethine ylides, which constructed biologically important tetrahydro‐γ‐carboline frameworks in high yields and excellent enantioselectivities (up to 83 % yield, 99:1 e.r.). This reaction not only represents the first application of 2‐indolylmethanols as 3C building blocks in catalytic asymmetric cycloadditions, but also has established an abnormal regioselectivity in indolylmethanol‐involved transformations.     

Enantio‐ and Diastereoselective Synthesis of Chiral Allenes by Palladium‐Catalyzed Asymmetric [3+2] Cycloaddition Reactions

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium‐catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio‐, enantio‐, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.     

An Efficient Synthesis of Optically Active trans‐(3R,4R)‐3‐Acetoxy‐4‐aryl‐1‐(chrysen‐6‐yl)azetidin‐2‐ones Using (+)‐Car‐3‐ene as a Chiral Auxiliary

An efficient enantioselective synthesis of 3‐acetoxy trans‐β‐lactams 7a and 7b via [2+2] cycloaddition reactions of imines 4a and 4b , derived from a polycyclic aromatic amine and bicyclic chiral acid obtained from (+)‐car‐3‐ene, is described. The cycloaddition was found to be highly enantioselective, producing only trans‐(3R,4R)‐N‐azetidin‐2‐one in very good yields. This is the first report of the synthesis of enantiomerically pure trans‐β‐lactams 7a and 7b with a polycyclic aromatic substituent at N(1) of the azetidin ring.