Diversified Cycloisomerization/Diels–Alder Reactions of 1,6‐Enynes through Bimetallic Relay Asymmetric Catalysis

We report the combination of transition‐metal‐catalyzed diversified cycloisomerization of 1,6‐enynes with chiral Lewis acid promoted asymmetric Diels–Alder reaction to realize asymmetric cycloisomerization/Diels–Alder relay reactions of 1,6‐enynes with electron‐deficient alkenes. A broad spectrum of chiral [5,6]‐bicyclic products could be acquired in high yields (up to 99 %) with excellent diastereoselectivy (>19:1 dr) and enantioselectivity (up to 99 % ee).     

RhI‐Catalyzed Cyclizative Addition Reaction of 1,6‐Enyne and Sulfonyl Chloride by Carbophilic Activation

The π‐acid‐catalyzed cyclizations of 1,n‐enynes by carbophilic activation have been extensively studied and appear as highly attractive processes, yet the cases within a catalytic cycle based on redox principle are rare. Herein, we report the cyclizative addition reactions of 1,6‐enynes and sulfonyl chlorides by using a [Rh(cod)Cl/dppf] (dppf=1,1′‐bis(diphenylphosphino)ferrocene) catalyst system. The process features the involvement of oxidative addition of sulfonyl chloride to Rh^I catalyst, which generates [(dppf)(RSO₂)RhCl₂] as a π‐acid species to trigger cyclizative addition in a 6‐endo‐dig manner by carbophilic activation. Moreover, the catalytic protocol is also applicable to 1,6‐diene analogues.     

Pd‐Catalyzed Cycloisomerization of 4‐Aza‐1,6‐enynes to 3‐Aza‐bicyclo[4.1.0]hept‐2‐enes

A method for the synthesis of bicyclo[4.1.0]heptenes from 1,6‐enynes through Pd‐catalyzed cycloisomerization has been developed. N‐ and O‐tethered 1,6‐enynes were successfully transformed to their corresponding 3‐aza‐ and 3‐oxabicyclo[4.1.0]heptenes in reasonable‐to‐high yields using the catalysts [PdCl₂(CH₃CN)₂]/P(OPh)₃ or [Pd(maleimidate)₂(PPh₃)₂] in toluene. The computational calculations using density functional theory indicate that [PdCl₂{P(OPh)₃}] in the oxidation state Pd^II acts as the active catalyst species for the formation of 3‐azabicyclo[4.1.0]heptenes through 6‐endo‐dig cyclization.     

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.     

Divergent Gold(I)‐Catalyzed Skeletal Rearrangements of 1,7‐Enynes

The gold(I) complex catalyzed cycloisomerization and skeletal rearrangement of 1,n‐enynes (n=5–7) is a powerful methodology for the efficient synthesis of complex molecular architectures. In contrast to 1,6‐enynes, readily accessible homologous 1,7‐enynes are largely unexplored in such transformations. Here, the divergent skeletal rearrangement of all‐carbon 1,7‐enynes by catalysis with a cationic gold(I) complex is reported. Depending on electronic and steric factors, differently substituted 1,7‐enynes react via different carbocations formed from a common gold carbene intermediate to yield on the one hand novel exocyclic allenes and on the other hand tricyclic hexahydro‐anthracenes through a novel dehydrogenative Diels–Alder reaction.     

An Ylide Transformation of Rhodium(I) Carbene: Enantioselective Three‐Component Reaction through Trapping of Rhodium(I)‐Associated Ammonium Ylides by β‐Nitroacrylates

The chiral Rh^I–diene‐catalyzed asymmetric three‐component reaction of aryldiazoacetates, aromatic amines, and β‐nitroacrylates was achieved to obtain γ‐nitro‐α‐amino‐succinates in good yields and with high diastereo‐ and enantioselectivity. This reaction is proposed to proceed through the enantioselective trapping of Rh^I‐associated ammonium ylides by nitroacrylates. This new transformation represents the first example of Rh^I‐carbene‐induced ylide transformation.     

Cyclobutene Formation in PtCl2‐Catalyzed Cycloisomerizations of Heteroatom‐Tethered 1,6‐Enynes

Aza(oxa)bicyclo[3.2.0]heptenes are accessed through the PtCl₂‐catalyzed cycloisomerizations of heteroatom‐tethered 1,6‐enynes featuring a terminal alkyne and amide as the solvent. It is shown that the weak coordinating properties of the solvent and alkyl substituent(s) at the propargylic carbon atom favor the formation of cyclobutenes instead of other possible cycloisomerization products such as 1,3‐diene derivatives or cyclopropane‐fused heterocycles.     

Rhodium(I)‐Catalyzed Cycloisomerization of Benzylallene‐Alkynes through CH Activation

The efficient Rh^I‐catalyzed cycloisomerization of benzylallene‐alkynes produced the tricyclo[9.4.0.0^3,8]pentadecapentaene skeleton through a C? H bond activation in good yields. A plausible reaction mechanism proceeds via oxidative addition of the acetylenic C? H bond to Rh^I, an ene‐type cyclization to the vinylidenecarbene–Rh^I intermediate, and an electrophilic aromatic substitution with the vinylidenecarbene species. It was proposed based on deuteration and competition experiments.     

Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing enynes

A Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing 1,n‐enynes to give three different types of compounds is discussed. 1,6‐enynes with a stoichiometric amount of FeX₃ provided cis‐hydrobenzofurans with moderate stereoselectivity, whereas the reaction with TMSX (X = Cl, Br) as the halide source in the presence of Fe catalyst improved the stereoselectivity of halide addition highly. The alkyl vs aryl shows difference that the reaction of 1,6‐enynes bearing an alkylethynyl group gave meta alkenated phenols (2 examples) whereas a similar reaction of 1,6‐enynes with an arylethynyl group delivered only cis‐hydrobenzofurans (12 examples). 1,7‐enynes afforded tricyclic products (4 examples). The different reactivity of 1,6‐ and 1,7‐enynes is probably influenced by the formation of a six‐membered chair‐like intermediate in 1,6‐enynes.     

Contrasted effect of CO on the metal‐catalyzed cycloisomerization of O‐tethered enynes derived from monoterpenes

The CO‐bubbling effect in cycloisomerization reactions of enynes derived from monoterpenes has been studied using PtCl₂, [Rh₂Cl₂(CO)₄] and AuCl₃ as catalytic systems. All the precursors are efficient catalysts for the cycloisomerization of O‐tethered enynes. The reaction proceeds through exo‐dig and endo‐dig pathways, which are consistent with the exclusive coordination of the alkyne triple bond to the metal center. The CO ligand not only increases the reaction rates but also induces significant variations in the two reaction pathways. Notably, this effect is also strongly dependent on the nature of the starting enyne. Copyright © 2011 John Wiley & Sons, Ltd.     

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.     

Catalyst‐Dependent Divergent Synthesis of Pyrroles from 3‐Alkynyl Imine Derivatives: A Noncarbonylative and Carbonylative Approach

A novel Ru⁰‐ and Rh^I‐catalyzed noncarbonylative and carbonylative cycloisomerization of readily available 3‐alkynyl imine derivatives has been developed to provide 3,4‐fused or nonfused pyrrole derivatives efficiently in moderate to excellent yields. The key steps involve the formation of a ruthenium carbenoid intermediate or a rhodacycle intermediate, respectively. In these reactions, CO can serve as a ligand or a reagent.     

Rhodium‐Catalyzed Hydroformylation of 1,1‐Disubstituted Allenes Employing the Self‐Assembling 6‐DPPon System

A rhodium‐catalyzed hydroformylation of 1,1‐disubstituted allenes is reported. Using a Rh^I/6‐DPPon catalyst system, one can obtain β,γ‐unsaturated aldehydes in high regio‐ and chemoselectivity. The Z‐configured product is formed with up to >95 % selectivity when unsymmetrically 1,1‐disubstituted allenes are submitted to the reaction conditions. This is the first time that these interesting building blocks are accessible by hydroformylation of allenes. The utility of this methodology is demonstrated by further transformations of one of the obtained products.     

Regio‐ and Enantioselective Rhodium‐Catalyzed Addition of 1,3‐Diketones to Allenes: Construction of Asymmetric Tertiary and Quaternary All Carbon Centers

An unprecedented highly regio‐ and enantioselective rhodium‐catalyzed addition of 1,3‐diketones to terminal and 1,1‐disubstituted allenes furnishing asymmetric tertiary and quaternary all‐carbon centers is reported. By applying a Rh^I/phosphoramidite/TFA catalytic system under mild conditions, the desired chiral branched α‐allylated 1,3‐diketones could be obtained in good to excellent yields, with perfect regioselectivity and in high enantioselectivity. The reaction shows a broad functional‐group tolerance on both reaction partners highlighting its synthetic potential.     

First Stabilization of 14‐Electron Rhodium(I) Complexes by Hemichelation

Hemichelation is emerging as a new mode of coordination where non‐covalent interactions crucially contribute to the cohesion of electron‐unsaturated organometallic complexes. This study discloses an unprecedented demonstration of this concept to a Group 9 metal, that is, Rh^I. The syntheses of new 14‐electron Rh^I complexes were achieved by choosing the anti‐[(η⁶:η⁶‐fluorenyl){Cr(CO)₃}₂] anion as the ambiphilic hemichelating ligand, which was treated with [{Rh(nbd)Cl}₂] (nbd=norbornadiene) and [{Rh(CO)₂Cl}₂]. The new T‐shaped Rh^I hemichelates were characterized by analytical and structural methods. Investigations using the methods of the DFT and electron‐density topology analysis (NCI region analysis, QTAIM theory) confirmed the closed‐shell, non‐covalent and attractive characters of the interaction between the Rh^I center and the proximal Cr(CO)₃ moiety. This study shows that, by appropriate tuning of the electronic properties of the ambiphilic ligand, truly coordination‐unsaturated Rh^I complexes can be synthesized in a manageable form.     

The Challenge of Linear (E)‐Enones in the Rh‐Catalyzed,Asymmetric 1,4‐Addition Reaction of Phenylboronic Acid: A DFT Computational Analysis

Why are linear (E)‐enones such challenging substrates in the Rh‐catalyzed asymmetric arylation with boronic acids, which is one of the most important asymmetric catalysis methods? DFT computations show that these substrates adopt a specific conformation in which the largest substituent is antiperiplanar to Rh^I π‐complexed with the C?C bond within the enantioselectivity‐determining carborhodation transition state. Additionally, for such structures, there is a strong, but not exclusive, preference for s‐cis enone conformation. This folding minimizes steric interactions between the substrate and the ligand, and hence reduces the enantioselectivity. This idea is further confirmed by investigating three computation‐only substrate “probes”, one of which is capable of double asymmetric induction, and a recent computationally designed 1,5‐diene ligand. On average, excellent agreement between predicted and experimental enantioselectivity was attained by a three‐pronged approach: 1) thorough conformational search within ligand and substrate subunits to locate the most preferred carborhodation transition state; 2) including dispersion interaction and long‐range corrections by SMD/ωB97xD/DGDZVP level of theory; and 3) full substrate and ligand modeling. Based on the results, a theory‐enhanced enantioselectivity model that is applicable to both chiral diene and diphosphane ligands is proposed.     

Enzyme‐ and Ruthenium‐Catalyzed Enantioselective Transformation of α‐Allenic Alcohols into 2,3‐Dihydrofurans

An efficient one‐pot method for the enzyme‐ and ruthenium‐catalyzed enantioselective transformation of α‐allenic alcohols into 2,3‐dihydrofurans has been developed. The method involves an enzymatic kinetic resolution and a subsequent ruthenium‐catalyzed cycloisomerization, which provides 2,3‐dihydrofurans with excellent enantioselectivity (up to >99 % ee). A ruthenium carbene species was proposed as a key intermediate in the cycloisomerization.     

2‐(2′‐Pyridyl)‐4,6‐diphenylphosphinine versus 2‐(2′‐Pyridyl)‐4,6‐diphenylpyridine: Synthesis,Characterization, and Reactivity of Cationic RhIII and IrIII Complexes Based on Aromatic Phosphorus Heterocycles

The bidentate P,N hybrid ligand 1 allows access for the first time to novel cationic phosphinine‐based Rh^III and Ir^III complexes, broadening significantly the scope of low‐coordinate aromatic phosphorus heterocycles for potential applications. The coordination chemistry of 1 towards Rh^III and Ir^III was investigated and compared with the analogous 2,2′‐bipyridine derivative, 2‐(2′‐pyridyl)‐4,6‐diphenylpyridine ( 2 ), which showed significant differences. The molecular structures of [RhCl(Cp*)( 1 )]Cl and [IrCl(Cp*)( 1 )]Cl (Cp*=pentamethylcyclopentadienyl) were determined by means of X‐ray diffraction and confirm the mononuclear nature of the λ³‐phosphinine–Rh^III and Ir^III complexes. In contrast, a different reactivity and coordination behavior was found for the nitrogen analogue 2 , especially towards Rh^III as a bimetallic ion pair [RhCl(Cp*)( 2 )]⁺[RhCl₃(Cp*)]^? is formed rather than a mononuclear coordination compound. [RhCl(Cp*)( 1 )]Cl and [IrCl(Cp*)( 1 )]Cl react with water regio‐ and diastereoselectively at the external P?C double bond, leading exclusively to the anti‐addition products [MCl(Cp*)( 1 H ? OH)]Cl as confirmed by X‐ray crystal‐structure determination.     

Synthesis of Spirocyclic Enones by Rhodium‐Catalyzed Dearomatizing Oxidative Annulation of 2‐Alkenylphenols with Alkynes and Enynes

The dearomatizing oxidative annulation of 2‐alkenylphenols with alkynes and enynes proceeds with high yields and regioselectivities under Rh^III catalysis. These reactions are successful using Cu(OAc)₂ or air as the stoichiometric oxidant, and provide spirocyclic enones, the basic ring system of which appears in several natural products. Application of this process to the preparation of a highly functionalized tetracycle is also demonstrated.     

Rhodium‐Catalyzed Dynamic Kinetic Asymmetric Allylation of Phenols and 2‐Hydroxypyridines

Inspired by the mechanistic studies of rhodium‐catalyzed atom‐economic addition of carboxylate acids to allenes, a rhodium‐catalyzed dynamic kinetic asymmetric allylation of different nucleophiles with racemic allylic carbonates has been developed. High regio‐ and enantioselectivities can be obtained under neutral conditions and, furthermore, the chemoselectivities can be controlled by different diphosphine ligands. (R,R)‐QuinoxP* leads to selective O‐allylation of phenols, whereas when embedding (S,S)‐DIOP as the ligand, 2‐naphthol is ortho‐C‐allylated for the first time in high enantioselectivity. To this end, hydroxypyridines can be N‐allylated by Rh^I/(S)‐DTBM‐Segphos via the same intermediate as in the previously reported atom‐economic addition to allenes.