Mechanism and regioselectivity of reductive elimination of pi-allylcopper (III) intermediates

Reductive elimination of a pi-allylcopper(III) compound leading to the formation of a C-C bond on an allylic terminal has been considered to occur via the corresponding sigma-allylcopper(III) species. The present B3LYP density functional study has shown however that the C-C bond formation occurs directly from the pi-allyl complex via an enyl[sigma+pi]-type transition state, which has structural features different from a simple sigma-allylcopper(III) intermediate. In the case of unsymmetrically substituted pi-allylcopper(III) compound that has a partial sigma-allylcopper(III) structure, the reductive elimination occurs preferentially at the sigma-bonded allylic terminal since, in this way, the copper atom can recover most effectively its d-electrons shared with the allyl system. The regioselectivity of the reductive elimination of a substituted pi-allylcopper(III) intermediate is mainly controlled by the electronic effect, and correlated well to the Hammett sigma(p)(+) constant. The analyses revealed mechanistic kinship between the allylic substitution and the conjugate addition reaction of organocopper reagents.     

A DFT Study on the Conversion of Aryl Iodides to Alkyl Iodides: Reductive Elimination of R−I from Alkylpalladium Iodide Complexes with Accessible β‐Hydrogens

DFT calculations have been performed on the palladium‐catalyzed carboiodination reaction. The reaction involves oxidative addition, alkyne insertion, C?N bond cleavage, and reductive elimination. For the alkylpalladium iodide intermediate, LiOtBu stabilizes the intermediate in non‐polar solvents, thus promoting reductive elimination and preventing β‐hydride elimination. The C?N bond cleavage process was explored and the computations show that PPh₃ is not bound to the Pd center during this step. Experimentally, it was demonstrated that LiOtBu is not necessary for the oxidative addition, alkyne insertion, or C?N bond cleavage steps, lending support to the conclusions from the DFT calculations. The turnover‐limiting steps were found to be C?N bond cleavage and reductive elimination, whereas oxidative addition, alkyne insertion, and formation of the indole ring provide the driving force for the reaction.     

Mechanism and Selectivity of RuII‐ and RhIII‐Catalyzed Oxidative Spiroannulation of Naphthols and Phenols with Alkynes through a C−H Activation/Dearomatization Strategy

The ruthenium‐ and rhodium‐catalyzed oxidative spiroannulation of naphthols and phenols with alkynes was investigated by means of density functional theory calculations. The results show that the reaction undergoes O?H deprotonation/C(sp²)?H bond cleavage through a concerted metalation–deprotonation mechanism/migratory insertion of the alkyne into the M?C bond to deliver the eight‐membered metallacycle. However, the dearomatization through the originally proposed enol–keto tautomerization/C?C reductive elimination was calculated to be kinetically inaccessible. Alternatively, an unusual metallacyclopropene, generated from the isomerization of the eight‐membered metallacycle through rotation of the C?C double bond, was identified as a key intermediate to account for the experimental results. The subsequent C?C coupling between the carbene carbon atom and the carbon atom of the 2‐naphthol/phenol ring was calculated to be relatively facile, leading to the formation of the unexpected dearomatized products. The calculations reproduce quite well the experimentally observed formal [5+2] cycloaddition in the rhodium‐catalyzed oxidative annulation of 2‐vinylphenols with alkynes. The calculations show that compared with the case of 2‐alkenylphenols, the presence of conjugation effects and less steric repulsion between the phenol ring and the vinyl moiety make the competing reductive oxyl migration become dominant, which enables the selectivity switch from the spiroannulation to the formal [5+2] cycloaddition.     

One‐Pot Synthesis of Highly Substituted Polyheteroaromatic Compounds by Rhodium(III)‐Catalyzed Multiple CH Activation and Annulation

A new method for the synthesis of highly substituted naphthyridine‐based polyheteroaromatic compounds in high yields proceeds through rhodium(III)‐catalyzed multiple C? H bond cleavage and C? C and C? N bond formation in a one‐pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π‐conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation‐assisted ortho C? H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.     

Nickel‐Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines

A nickel‐catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium‐catalyzed process in that the nickel–carbon bond is converted into a C−H bond to release the product through protonation instead of hydride donation followed by C−H reductive elimination on Pd.     

RhV‐Nitrenoid as a Key Intermediate in RhIII‐Catalyzed Heterocyclization by CH Activation: A Computational Perspective on the Cycloaddition of Benzamide and Diazo Compounds

A mechanistic study of the substituent‐dependent ring formations in Rh^III‐catalyzed C?H activation/cycloaddition of benzamide and diazo compounds was carried out by using DFT calculations. The results indicated that the decomposition of the diazo is facilitated upon the formation of the five‐membered rhodacycle, in which the Rh^III center is more electrophilic. The insertion of carbenoid into Rh?C(phenyl) bond occurs readily and forms a 6‐membered rhodacycle, however, the following C?N bond formation is difficult both kinetically and thermodynamically by reductive elimination from the Rh^III species. Instead, the Rh^V‐nitrenoid intermediate could be formed by migration of the pivalate from N to Rh, which undergoes the heterocyclization much more easily and complementary ring‐formations could be modulated by the nature of the substituent at the α‐carbon. When a vinyl is attached, the stepwise 1,3‐allylic migration occurs prior to the pivalate migration and the 8‐membered ring product will be formed. On the other hand, the pivalate migration becomes more favorable for the phenyl‐contained intermediate because of the difficult 1,3‐allylic migration accompanied by dearomatization, thus the 5‐membered ring product was formed selectively.     

Manganese(I)‐Catalyzed C−H Activation: The Key Role of a 7‐Membered Manganacycle in H‐Transfer and Reductive Elimination

Manganese‐catalyzed C?H bond activation chemistry is emerging as a powerful and complementary method for molecular functionalization. A highly reactive seven‐membered Mn^I intermediate is detected and characterized that is effective for H‐transfer or reductive elimination to deliver alkenylated or pyridinium products, respectively. The two pathways are determined at Mn^I by judicious choice of an electron‐deficient 2‐pyrone substrate containing a 2‐pyridyl directing group, which undergoes regioselective C?H bond activation, serving as a valuable system for probing the mechanistic features of Mn C?H bond activation chemistry.     

Understanding the Mechanisms of Unusually Fast HH,CH,and CC Bond Reductive Eliminations from Gold(III) Complexes

Carbon–carbon bond reductive elimination from gold(III) complexes are known to be very slow and require high temperatures. Recently, Toste and co‐workers have demonstrated extremely rapid C?C reductive elimination from cis‐[AuPPh₃(4‐F‐C₆H₄)₂Cl] even at low temperatures. We have performed DFT calculations to understand the mechanistic pathway for these novel reductive elimination reactions. Direct dynamics calculations inclusive of quantum mechanical tunneling showed significant contribution of heavy‐atom tunneling (>25 %) at the experimental reaction temperatures. In the absence of any competing side reactions, such as phosphine exchange/dissociation, the complex cis‐[Au(PPh₃)₂(4‐F‐C₆H₄)₂]⁺ was shown to undergo ultrafast reductive elimination. Calculations also revealed very facile, concerted mechanisms for H?H, C?H, and C?C bond reductive elimination from a range of neutral and cationic gold(III) centers, except for the coupling of sp³ carbon atoms. Metal–carbon bond strengths in the transition states that originate from attractive orbital interactions control the feasibility of a concerted reductive elimination mechanism. Calculations for the formation of methane from complex cis‐[AuPPh₃(H)CH₃]⁺ predict that at ?52 °C, about 82 % of the reaction occurs by hydrogen‐atom tunneling. Tunneling leads to subtle effects on the reaction rates, such as large primary kinetic isotope effects (KIE) and a strong violation of the rule of the geometric mean of the primary and secondary KIEs.     

Competitive Gold‐Activation Modes in Terminal Alkynes: An Experimental and Mechanistic Study

The competition between π‐ and dual σ,π‐gold‐activation modes is revealed in the gold(I)‐catalyzed heterocyclization of 1‐(o‐ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)]⁺ (IPr=2,6‐bis(diisopropylphenyl)imidazol‐2‐ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu₃)]⁺ favors intermediate σ,π species. In this experimental and mechanistic study, which includes kinetic and cross‐over experiments, several σ‐gold, σ,π‐gold, and other gold polynuclear reaction intermediates have been isolated and identified by NMR spectroscopy, X‐ray diffraction, or MALDI spectrometry. The ligand control in the simultaneous or alternative π‐ and σ,π‐activation modes is also supported by deuterium‐labeling experiments.     

Mechanism and Origins of Diastereo- and Regioselectivities of Palladium-Catalyzed Remote Diborylative Cyclization of Dienes via Chain-Walking Strategy

Density functional theory calculations have been performed to investigate the palladium-catalyzed remote diborylative cyclization of dienes. The computations reveal that the reaction proceeds through a rarely explored Pd(II)/Pd(IV) catalytic cycle, and the formal σ-bond metathesis between the alkylpalladium intermediate and B₂pin₂ occurs via the pathway of the B−B oxidative addition/C−B reductive elimination involving the high-valent Pd(IV) species. The diastereoselectivity is determined by the migratory insertion into the Pd−C bond, which is mainly due to the combination of the torsional strain effect, steric repulsion and C−H—O hydrogen-bonding interaction. The steric hindrance around the reacting carbon group in the C−B reductive elimination turns out to be a key factor to provide the driving force of the chain walking of the Pd center to the terminal primary carbon position, enabling the experimentally observed remote regioselectivity.     

The Mechanism of NO Bond Cleavage in Rhodium‐Catalyzed CH Bond Functionalization of Quinoline N‐oxides with Alkynes: A Computational Study

Metal‐catalyzed C?H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N‐oxide is used as an arene source in C?H activation studies, the N?O bond can act as a directing group as well as an O‐atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N?O bond and alkynes, which results in C?H activation and O‐atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh?C bond, a reductive elimination to form an oxazinoquinolinium‐coordinated Rh^I intermediate, an oxidative addition to break the N?O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop‐1‐yn‐1‐ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1‐phenyl‐2‐quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity‐determining step. These calculated data are consistent with the experimental observations.     

A one-pot diastereoselective synthesis of cis-3-hexene-1,6-diols via an unusually reactive organozinc intermediate

A highly diastereoselective method for the synthesis of cis-3-hexene-1,6-diols has been developed. This new reaction proceeds with excellent control of diastereoselectivity over four stereocenters and the double bond geometry. The diols are made in a one-pot procedure involving hydroboration of a terminal alkyne and transmetalation to zinc to give a divinylzinc intermediate. This intermediate undergoes reductive elimination, forming a C=C bond. In the absence of a trapping reagent, diene is liberated (70% yield); however, in the presence of ketones or aldehydes, the proposed intermediate metallocyclopentene is trapped via a double insertion of the carbonyl substrate. Workup provides the diols in 47-86% yield.     

Oxidative Interception of the Hydroamination Pathway: A Gold‐Catalyzed Diamination of Alkenes

A complimentary diamination of alkenes by using homogeneous gold catalysts is described. The reaction is one of very few examples of homogeneous gold oxidation catalysis and proceeds with high selectivity under mild conditions. Individual steps of the suggested catalytic cycle were investigated on isolated model gold complexes, and new pathways for gold‐catalyzed amination reactions were established. The key step is an intramolecular alkyl–nitrogen bond formation from a gold(III) intermediate. This process validates the concept of reductive elimination from high oxidation catalyst states for this type of C? N bond forming reactions.     

Rhenium(I)‐Catalyzed ortho‐C−H Addition to Bicyclic Alkenes

Hydroarylation of bicyclic alkenes has been developed using a low‐valent Re^I‐catalyzed, directing group‐assisted C?H bond activation strategy. The addition of sodium acetate significantly improves the reaction efficiency; moreover, bicyclic alkenes such as 7‐oxa and aza benzonorbornadienes worked efficiently under this reaction condition. Preliminary mechanistic studies suggest that, after the alkene insertion, the rhenacycle preferentially undergoes protonolysis rather than reductive elimination.     

Rhodium(I)‐Catalyzed Cyclization of Allenynes with a Carbonyl Group through Unusual Insertion of a CO Bond into a Rhodacycle Intermediate

Rhodium(I)‐catalyzed cyclization of allenynes with a tethered carbonyl group was investigated. An unusual insertion of a C?O bond into the C(sp²)–rhodium bond of a rhodacycle intermediate occurs via a highly strained transition state. Direct reductive elimination from the obtained rhodacyle intermediate proceeds to give a tricyclic product containing an 8‐oxabicyclo[3.2.1]octane skeleton, while β‐hydride elimination from the same intermediate gives products that contain fused five‐ and seven‐membered rings in high yields.     

Rhodium‐Catalyzed Intramolecular C−H Silylation by Silacyclobutanes

Silacyclobutane was discovered to be an efficient C?H bond silylation reagent. Under the catalysis of Rh^I/TMS‐segphos, silacyclobutane undergoes sequential C?Si/C?H bond activations, affording a series of π‐conjugated siloles in high yields and regioselectivities. The catalytic cycle was proposed to involve a rarely documented endocyclic β‐hydride elimination of five‐membered metallacycles, which after reductive elimination gave rise to a Si?Rh^I species that is capable of C?H activation.     

Palladium-catalyzed oxidative aryltrifluoromethylation of activated alkenes at room temperature

A palladium-catalyzed intramolecular oxidative aryltrifluoromethylation reaction of activated alkenes has been explored. The reaction allows for an efficient synthesis of a variety of CF(3)-containing oxindoles. Preliminary mechanistic study indicated that the reaction involves a C(sp(3))-Pd(IV)(CF(3)) intermediate, which undergoes reductive elimination to afford a C(sp(3))-CF(3) bond.     

Rhodium(III)-Catalyzed Asymmetric [4+1] and [5+1] Annulation of Arenes and 1,3-Enynes: A Distinct Mechanism of Allyl Formation and Allyl Functionalization

We report chiral Rh^III cyclopentadienyl-catalyzed enantioselective synthesis of lactams and isochromenes through oxidative [4+1] and [5+1] annulation, respectively, between arenes and 1,3-enynes. The reaction proceeds through a C−H activation, alkenyl-to-allyl rearrangement, and a nucleophilic cyclization cascade. The mechanisms of the [4+1] annulations were elucidated by a combination of experimental and computational methods. DFT studies indicated that, following the C−H activation and alkyne insertion, a Rh^III alkenyl intermediate undergoes δ-hydrogen elimination of the allylic C−H via a six-membered ring transition state to produce a Rh^III enallene hydride intermediate. Subsequent hydride insertion and allyl rearrangement affords several rhodium(III) allyl intermediates, and a rare Rh^III η⁴ ene-allyl species with π-agostic interaction undergoes SN₂′-type external attack by the nitrogen nucleophile, instead of C−N reductive elimination, as the stereodetermining step.     

Fluorinated Vinylsilanes from the Copper‐Catalyzed Defluorosilylation of Fluoroalkene Feedstocks

Herein, a copper‐catalyzed C?F bond defluorosilylation reaction of tetrafluoroethylene and other polyfluoroalkenes is described. Mechanistic studies, based on a series of stoichiometric reactions with copper complexes, revealed that the key steps of this defluorosilylation reaction are 1) the 1,2‐addition of a silylcopper intermediate to the polyfluoroalkene and 2) a subsequent selective β‐fluorine elimination, which generates a Cu?F species. The β‐fluorine elimination is facilitated by Lewis acidic F?Bpin, which is generated in situ during the defluorosilylation.     

One‐Pot Synthesis of Highly Substituted Polyheteroaromatic Compounds by Rhodium(III)‐Catalyzed Multiple C?H Activation and Annulation

A new method for the synthesis of highly substituted naphthyridine‐based polyheteroaromatic compounds in high yields proceeds through rhodium(III)‐catalyzed multiple C H bond cleavage and C C and C N bond formation in a one‐pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π‐conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation‐assisted ortho C H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.