[(NHC)AuCl]-catalyzed Meyer-Schuster rearrangement: scope and limitations

An efficient catalytic system allowing for the synthesis of a variety of α,β-unsaturated ketones has been developed. [(NHC)AuCl] (NHCN-heterocyclic carbene) in the presence of a silver(I) salt was found to catalyze the Meyer-Schuster rearrangement, leading to α,β-unsaturated ketones from easily accessible propargylic alcohols in high yields. Catalysis was performed in a 2:1 mixture of methanol and water at 60 °C and afforded good yields even for tertiary alcohols and sterically demanding substrates. Thorough evaluation of the present catalytic system uncovered that it was unsuitable for terminal alkynes and primary alcohols. In these cases low yields of the target molecules were obtained due to the formation of unexpected by-products.     

Au(I)- and Pt(II)-catalyzed cycloetherification of omega-hydroxy propargylic esters

Depending on the nature of the metal catalyst, omega-hydroxy propargylic acetates choose between alternative cycloetherification manifolds to produce functionalized heterocycles in high yields. AuCl catalyzes the formation of oxacyclic enol acetates, whereas [Cl(2)Pt(CH(2)CH(2))]2 (Zeise's dimer) will induce a propargylic substitution via an unprecedented S(N)2'-type allenic substitution from within a chelated square planar cationic Pt(II) complex.     

Platinum- and gold-catalyzed cycloisomerization reactions of hydroxylated enynes

Exposure of enynes containing a hydroxyl group at one of the propargylic positions to catalytic amounts of either PtCl2 or (PPh3)AuCl/AgSbF6 results in a selective rearrangement with formation of bicyclo[3.1.0]hexan-3-one derivatives. The same products are obtained by a "one-pot" process on treatment of an alkynal with allylchlorodimethylsilane (4) and PtCl2 via a reaction cascade involving an initial platinum-catalyzed allylation followed by the cycloisomerization of the homoallylic alcohol formed in situ. This novel skeletal reorganization process was implemented into a concise total synthesis of the terpenes sabinone (18) and sabinol (19). Furthermore it is shown that conversion of the hydroxylated enynes into the corresponding acetates followed by reaction with a cationic gold catalyst formed from (PPh3)AuCl and AgSbF6 opens entry into isomeric products bearing the ketone function at the C-2 position of the bicyclo[3.1.0]hexane skeleton. The outcome of a deuterium labeling experiment and the analysis of the stereochemical course of the cycloisomerization reaction are consistent with the formation of cyclopropylmethyl platinum carbene species as reactive intermediates.     

(NHC)AuI]-catalyzed rearrangement of allylic acetates

[(NHC)AuCl] complexes (NHC = N-heterocyclic carbene), in conjunction with a silver salt, were found to efficiently catalyze the rearrangement of allylic acetates under both conventional and microwave-assisted heating. The optimization of several reaction parameters (solvent, silver salt, and ligand) as well as a study of the reaction scope are reported. The steric hindrance of the ligand bound to gold was found crucial for the outcome of the reaction as only extremely bulky ligands permitted the isomerization.     

Isolable tris(alkyne) and bis(alkyne) complexes of gold(I)

Golden trefoils: Tris(alkyne)gold complex [(coct)(3)Au][SbF(6)] (see picture; 1-SbF(6)) can be synthesized from cyclooctyne (coct) and AuSbF(6) generated in situ. Treatment of AuCl with cyclooctyne led to the bis(alkyne)gold complex [Au(coct)(2)Cl] (2). DFT analysis indicates that the cyclooctyne ligands are net electron donors in 1 but overall electron acceptors in 2. AuSbF(6) is shown to mediate [2+2+2] cycloaddition reactions of alkynes.     

Synthesis and structural characterisation of linear Au(I) N-heterocyclic carbene complexes: New analogues of the Au(I) phosphine drug Auranofin

The synthesis and characterisation of a series of neutral Au(I) N-heterocyclic carbene complexes [(NHC)AuX] (X = Cl and 2′,3′,4′,6′-tetra-O-acetyl-β-d-glucopyranosyl-1-thiolato) are reported. The chloro complexes were synthesised either by reaction of the appropriate 1,3-dialkylimidazol-2-ylidene with [(Me₂S)AuCl] or by transmetallation between the appropriate Ag(I)–NHC complex and [(Me₂S)AuCl]. The 2′,3′,4′,6′-tetra-O-acetyl-β-d-glucopyranosyl-1-thiolato complexes were prepared from the appropriate [(NHC)Au(I)Cl] complex and 2′,3′,4′,6′-tetra-O-acetyl-1-thio-β-d-glucopyranose under basic conditions. A cationic Au(I)–NHC triphenylphosphine adduct was also prepared. Structural studies (X-ray diffraction) of a number of the complexes show that in each case the gold atom is (quasi-) linearly two-coordinate, having C–Au–Cl, C–Au–S or C–Au–P coordination. In one case, a new phase of [(Cy₂Im)AuCl], the molecules pack pair-wise with a close Au⋯Au interaction (3.1566(6) Å). Preliminary studies show this complex is luminescent in the solid state.     

Understanding the cooperative NHC/LA catalysis for stereoselective annulation reactions with homoenolates. A DFT study

The role of Ti(Oi-Pr)(4) Lewis acid (LA) in the cooperative N-heterocyclic carbene (NHC)/LA catalyzed addition of enals to enones to yield cis-cyclopentenes has been investigated using DFT methods at the B3LYP/6-31G** computational level. Ti(IV) effectively catalyzes the reaction by formation of a complex with cinnamaldehyde 1, which favors the nucleophilic attack of NHC 5 on 1, and the subsequent proton abstraction to yield the extended Ti(IV)-Breslow intermediate 21. The nature of the metal involved in the LA catalyst plays a relevant role due to the more basic character of NHCs than aldehydes. Thus, strong LAs, such as Zn(OTf)(2), prevent the catalytic behavior of NHCs to form a very stable complex. The subsequent formation of a complex between chalcone 2 and the extended Ti(IV)-Breslow intermediate 21 favors the cis stereoselective C-C bond-formation. Analysis of the structures of Ti(IV)-complex precursors for the cis and trans C-C bond-formation steps allows for an explanation of the unexpected cis stereoselectivity.     

Distinguishing carbones from allenes by complexation to AuCl

Quantum chemical calculations have been performed for the dicoordinated carbon compounds C(PPh(3))(2), C(NHC(Me))(2), R(2) C=C=CR(2) (R = H, F, NMe(2)), C(3)O(2), C(CN)(2)(-) and N-methyl-substituted N-heterocyclic carbene (NHC(Me)). The geometries of the complexes in which the dicoordinated carbon molecules bind as ligands to one and two AuCl moieties have been optimized and the strength and nature of the metal-ligand interactions in the mono- and diaurated complexes were investigated by means of energy decomposition analysis. The goal of the study is to elucidate the differences in the chemical behavior between carbones, allenes and carbenes. The results show that carbones bind one and two AuCl species in η(1) fashion, whereas allenes bind them in η(2) fashion. Compounds with latent divalent carbon(0) character can coordinate in more than one way, with the dominant mode indicating the degree of carbone or allene character. The calculated structures of the mono- and diaurated tetraaminoallenes (TAAs) reveal that TAAs exhibit a chameleon-like behavior: The bonding situation in the equilibrium structure is best described as allene [(R(2)N)(2)]C=C=C[(NR(2))(2)] in which the central carbon atom is a tetravalent C(IV) species, but the reactivity suggests that TAAs should be considered as divalent C(0) compounds C{C[(NR(2))(2)]}(2), that is, as "hidden" carbones. Carbon suboxide binds one AuCl preferentially in the η(1) mode, whereas the equilibrium structures of the η(1)- and η(2)-bonded diaurated complex are energetically nearly degenerate. The doubly negatively charged isoelectronic carbone C(CN)(2)(2-) binds one and two AuCl very strongly in characteristic η(1) fashion. The N-heterocyclic carbene complex, [NHC(Me)(AuCl)], possesses a high bond dissociation energy (BDE) for the splitting off of AuCl. The diaurated NHC adduct, [NHC(Me)(AuCl)(2)], has two η(1)-bonded AuCl moieties that exhibit aurophilic attraction, which yield a moderate bond strength that might be large enough for synthesizing the complex. The BDE for the second AuCl in [NHC(Me)(AuCl)(2)] is clearly smaller than the values for the second AuCl in doubly aurated carbone complexes.     

Asymmetric Synthesis of Highly Substituted β‐Lactones through Oxidative Carbene Catalysis with LiCl as Cooperative Lewis Acid

The reaction of enals with β‐diketones, β‐ketoesters, and malonates bearing a β‐oxyalkyl substituent at the α‐position by oxidative NHC catalysis to provide highly substituted β‐lactones is described. Reactions occur with excellent diastereo‐ and enantioselectivity. The organo cascade comprises two C? C bond formations and one C? O bond formation. Up to four contiguous stereogenic centers including two fully substituted stereocenters are formed in the cascade.     

A Dimeric NHC–Silicon Monotelluride: Synthesis,Isomerization, and Reactivity

The reaction of the NHC–disilicon(0) complex [(I_Ar)Si=Si(I_Ar)] ( 1 , I_Ar=:C{N(Ar)C(H)}₂, Ar=2,6‐i Pr₂C₆H₃) with two equiv of elemental Te in toluene at room temperature for three days afforded a mixture of the first dimeric NHC–silicon monotelluride [(I_Ar)Si=Te]₂ ( 2 ) and its isomeric complex [(I_Ar)Si(μ‐Te)Si(I_Ar)=Te] ( 3 ). When the same reaction was performed for ten days, only 3 was isolated from the reaction mixture. Compound 1 reacted with four equiv of elemental Te in toluene for four weeks, which proceeded through the formation of 2 , 3 and the NHC–disilicon tritelluride complex [{(I_Ar)Si(=Te)}₂Te] ( 5‐Te ), to form the dimeric NHC–silicon ditelluride [(I_Ar)Si(=Te)(μ‐Te)]₂ ( 4 ). The reactions are in line with theoretical mechanistic studies for the formation of 4 . Compound 3 reacted with one equiv of elemental sulfur in toluene to form the first NHC–disilicon sulfur ditelluride complex [{(I_Ar)Si(=Te)}₂S] ( 5‐S ).     

A Dimeric NHC–Silicon Monotelluride: Synthesis,Isomerization, and Reactivity

The reaction of the NHC–disilicon(0) complex [(I_Ar)Si=Si(I_Ar)] ( 1 , I_Ar=:C{N(Ar)C(H)}₂, Ar=2,6‐i Pr₂C₆H₃) with two equiv of elemental Te in toluene at room temperature for three days afforded a mixture of the first dimeric NHC–silicon monotelluride [(I_Ar)Si=Te]₂ ( 2 ) and its isomeric complex [(I_Ar)Si(μ‐Te)Si(I_Ar)=Te] ( 3 ). When the same reaction was performed for ten days, only 3 was isolated from the reaction mixture. Compound 1 reacted with four equiv of elemental Te in toluene for four weeks, which proceeded through the formation of 2 , 3 and the NHC–disilicon tritelluride complex [{(I_Ar)Si(=Te)}₂Te] ( 5‐Te ), to form the dimeric NHC–silicon ditelluride [(I_Ar)Si(=Te)(μ‐Te)]₂ ( 4 ). The reactions are in line with theoretical mechanistic studies for the formation of 4 . Compound 3 reacted with one equiv of elemental sulfur in toluene to form the first NHC–disilicon sulfur ditelluride complex [{(I_Ar)Si(=Te)}₂S] ( 5‐S ).     

N‐Heterocyclic Carbene Catalyzed γ‐Dihalomethylenation of Enals by Single‐Electron Transfer

An N‐heterocyclic carbene (NHC) catalyzed dihalomethylenation of enals is described. It is a rare example of merging NHC catalysis with single‐electron chemistry, a challenging topic with limited previous success. The versatile carbon‐centered trihalomethyl radicals have been demonstrated, for the first time, to be compatible with an NHC‐bound intermediate, thus leading to efficient and regioselective intermolecular C?C bond formation. The mild process provides straightforward access to unsaturated δ,δ‐dihalo esters.     

Heterogeneous gold-catalyzed oxidative cross-coupling of propargylic acetates with arylboronic acids leading to (E)-α-arylenones

An efficient heterogeneous gold-catalyzed oxidative cross-coupling of propargylic acetates with arylboronic acids has been developed that proceeds smoothly in the presence of Selectfluor and provides a general and powerful tool for the preparation of various valuable α-arylenones with moderate to good yields, excellent E-selectivity, and recyclability of the gold catalyst. The reaction is the first example of heterogeneous gold-catalyzed arylative rearrangement of propargylic acetates for construction of complex enones.     

An N-heterocyclic carbene-catalyzed [8 + 3] annulation of tropone and enals via homoenolate

A novel protocol for the annulation of tropone to enals involving nucleophilic heterocyclic carbene (NHC) catalyzed homoenolate formation has been developed. Interestingly, the reaction led to bicyclic delta-lactones instead of the expected gamma-spirolactones, presumably by the uncommon [8 + 3] annulation pathway. The strategy works well with a variety of enals.     

A Comparison of the Stability and Reactivity of Diamido‐ and Diaminocarbene Copper Alkoxide and Hydride Complexes

The mononuclear N‐heterocyclic carbene (NHC) copper alkoxide complexes [(6‐NHC)CuOtBu] (6‐NHC=6‐MesDAC ( 1 ), 6‐Mes ( 2 )) have been prepared by addition of the free carbenes to the tetrameric tert‐butoxide precursor [Cu(OtBu)]₄, or by protonolysis of [(6‐NHC)CuMes] (6‐NHC=6‐MesDAC ( 3 ), 6‐Mes ( 4 )) with tBuOH. In contrast to the relatively stable diaminocarbene complex 2 , the diamidocarbene derivative 1 proved susceptible to both thermal and hydrolytic ring‐opening reactions, the latter affording [(6‐MesDAC)Cu(OC(O)CMe₂C(O)N(H)Mes)(CNMes)] ( 6 ). The intermediacy of [(6‐MesDAC)Cu(OH)] in this reaction was supported by the generation of Cu₂O as an additional product. Attempts to generate an isolable copper hydride complex of the type [(6‐MesDAC)CuH] by reaction of 1 with Et₃SiH resulted instead in migratory insertion to generate [(6‐MesDAC‐H)Cu(P(p‐tolyl)₃)] ( 9 ) upon trapping by P(p‐tolyl)₃. Migratory insertion was also observed during attempts to prepare [(6‐Mes)CuH], with [(6‐Mes‐H)Cu(6‐Mes)] ( 10 ) isolated, following a reaction that was significantly slower than in the 6‐MesDAC case. The longer lifetime of [(6‐Mes)CuH] allowed it to be trapped stoichiometrically by alkyne, and also employed in the catalytic semi‐reduction of alkynes and hydrosilylation of ketones.     

Tandem au-catalyzed 3,3-rearrangement-[2 + 2] cycloadditions of propargylic esters: expeditious access to highly functionalized 2,3-indoline-fused cyclobutanes

The treatment of readily available propargylic indole-3-acetates with a catalytic amount of AuCl(PPh3)/AgSbF6 leads to tandem activations of the propargylic esters and the in situ generated allenylic esters, resulting in expeditious access to highly functionalized cyclobutanes with fused 2,3-indoline and gamma-lactone rings and an exocyclic E-double bond through sequential 3,3-rearrangement and [2 + 2] cyclization.     

A new, easily recyclable arylating agent based on a diphosphino-digold(I) complex

The synthesis of two organogold(I) complexes, [(Au(NCN))2(dppbp)] (6) and [(Au(Phebox))2(dppbp)] (9), and their application in subsequent transmetalating reactions are described. A trinuclear organogold(I) complex, [(AuCl)3(tdpppb)] (4) is also reported, which exhibits a surprisingly high solubility in dichloromethane. It was found that 6 and 9 can cleanly transfer the anionic NCN-([C(6)H(3)(CH(2)NMe(2))2-2,6]-) or Phebox-([2,6-bis(oxazolinyl)phenyl]-) moiety to Ti(IV) and Pd(II) centers, respectively. The coproduct [(AuCl)2(dppbp)] (3, dppbp is [4-Ph(2)PC(6)H(4)]2 (1)) formed during this transmetalation reaction, precipitates almost quantitatively from the reaction mixture (toluene) and can thus be separated by simple filtration. In comparison, [AuCl(PPh3)], formed as the coproduct in the transmetalation reaction of [Au(NCN)(PPh3)] with metal salts, has a higher solubility in apolar solvents and thus is more difficult to separate from the resultant organometallic complex. Digold complex 6 has been characterized by NMR spectroscopy and crystallographic analyses. These analyses show that the two gold units are essentially independent. The formation of a dimetallic transmetalating agent based on gold(I) had no effect on its transmetalating properties.     

An atom-economic and selective ruthenium-catalyzed redox isomerization of propargylic alcohols. An efficient strategy for the synthesis of leukotrienes

Catalytic ruthenium complexes in conjunction with an indium cocatalyst and Bronsted acid isomerize primary and secondary propargylic alcohols in good yields to provide trans enals and enones exclusively. Readily available indenylbis(triphenylphosphine)ruthenium chloride, in the presence of indium triflate and camphorsulfonic acid, gives the best turnover numbers and reactivity with the broadest range of substrates. Deuterium labeling experiments suggest that the process occurs through propargylic hydride migration followed by protic cleavage of the resultant vinylruthenium intermediate. Application of this method to the synthesis of leukotriene B4 demonstrates its utility and extraordinary selectivity.     

A DFT study on the mechanism of gold(III)-catalyzed synthesis of highly substituted furans via [3, 3]-sigmatropic rearrangements and/or [1, 2]-acyloxy migration based on propargyl ketones

The mechanisms of gold(III)-catalyzed synthesis of highly substituted furans via [3,3]-sigmatropic rearrangements and/or [1,2]-acyloxy migration based on propargyl ketones have been investigated using density functional theory calculations at BHandHLYP/6-31G(d,p) (SDD for Au) level of theory. Solvent effects on these reactions were explored using calculations that included a polarizable continuum model (PCM) for the solvent (toluene). Two plausible pathways that lead to the formation of Au(III) vinyl carbenoid and an allenyl structure through [3,3]-sigmatropic rearrangements, [1,2]-acyloxy migration via oxirenium and dioxolenylium were performed. Our calculated results suggested: (1) the major pathway of the cycle causes an initial Rautenstrauch-type [1,2]-migration via oxirenium to form an Au(III) vinyl carbenoid. Subsequent cycloisomerization of this intermediate then provides the corresponding furan whether for the methyl-substituted propargylic acetates or the phenyl-substituted propargylic acetates; (2) for the methyl-substituted propargylic acetates, the formation of Au(III) vinyl carbenoid structures was the rate-determining step. However, intramolecular nucleophilic attack and subsequent cycloisomerization to give the final product was rate-determining for the phenyl-substituted propargylic acetates. The computational results are consistent with the experimental observations of Gevorgyan, et al. for gold(III)-catalyzed synthesis of highly substituted furans based on propargyl ketones.     

Pd-N-杂环卡宾化合物催化的Heck反应、Suzuki反应进展

Pd催化的C—C键偶联反应是形成碳—碳单键的重要反应之一.传统上,使用膦化合物为配体来调整催化活性及选择性.但大多数Pd-膦化合物对空气稳定性差,容易被氧化;在溶液中易于解离出膦配体而降低催化剂稳定性,通常需要给反应体系中加入较多的膦配体以保持催化剂的稳定性和活性.1991年发现的稳定N-杂环卡宾(NHC)类配体具有富含电子、给电子能力强,对金属配位能力强,结构易修饰等特点,使得金属-NHC化合物成为金属有机化学、催化等领域研究新的焦点.Pd-NHC化合物已经可催化多类有机反应,是继传统Pd-膦催化剂外的又一类高效催化剂.综述了近年来不同结构的NHC如单齿简单NHC、双齿NHC、含其它配位原子的NHC等配体与Pd的配合物在Heck反应、Suzuki反应等偶联反应中的应用.