Ni-catalyzed regiodivergent hydrophosphorylation of enynes

A regiodivergent hydrophosphorylation of enynes with phosphites has been developed using earth-abundant nickel catalyst. The manipulation of regioselectivity can be achieved by regulating the insertion order of alkyne bonds with (RO)₂P(O)–Ni–H or R₂P(O)O–Ni–H species, respectively. Under the Ni/Xantphos catalysis, 4,1-hydrophosphorylation is selectively obtained while the adding of acid can promote reactions towards 1,2-addition. By employing an additional Pd–H catalysis, 2,1-hydrophosphorylation is also an accessible task in one-pot reaction. Mechanistic studies and analysis have also been performed to interpret the origin of the regioselective regulation. This work highlights the arts in accessing different regioisomers by diverting common elementary reaction steps.     

Intramolecular hydroamination of conjugated enynes

An intramolecular hydroamination of conjugated enyne was developed using commercially available n-BuLi as a precatalyst. This hydroamination reaction led to products with allene and pyrrolidine functional groups. One of the enyne hydroamination products was successfully converted to natural products irniine and irnidine in three steps. The scope and mechanism of the enyne hydroamination are also discussed.     

Regioselective solvent-dependent benzannulation of conjugated enynes

The transformation of enynes under cobalt-catalysis leads to symmetrical benzannulation products in dichloromethane. In tetrahydrofuran the cobalt-catalysed reactions afforded the unprecedented unsymmetrical benzannulation products in moderate to good yields and good regioselectivities. In addition, cyclotrimerisation of the alkyne subunit can be realised when electron-deficient enynes are applied in the cobalt-catalysed transformations to generate 1,2,4-trivinylbenzene derivatives using tetrahydrofuran as solvent.     

Base-catalyzed intramolecular hydroamination of conjugated enynes

A de novo intramolecular hydroamination of conjugated enynes was developed using commercially available n-BuLi as a precatalyst. This hydroamination reaction successfully afforded allenyl-substituted pyrrolidines with up to 95% yield. One of the resulting allenyl pyrrolidines was converted to the natural products irniine and irnidine in three steps.     

Efficient and Z-selective cross-metathesis of conjugated enynes

[reaction: see text] The generation of a conjugated alkynyl alkylidene has been achieved using an allyl ether moiety as an intramolecular catalyst delivery vehicle. The reaction of this intermediate with alkenes and alkynes yields conjugated enynes with Z-selectivity.     

Enhanced reactivity of electron-deficient enynes in the palladium-catalyzed homo-benzannulation of conjugated enynes

We report the high reactivity of electron-deficient enynes in the homo-benzannulation of conjugated enynes in the presence of Pd(PPh3)4. The introduction of electron-withdrawing groups enabled us to carry out the benzannulation of 1-substituted enynes as well as 1,2- and 2,4-disubstituted enynes. Polysubstituted benzenes were prepared in a highly regioselective manner in good to excellent yields.     

The mechanistic puzzle of transition-metal-catalyzed skeletal rearrangements of enynes

Three pathways actually compete in metal-catalyzed cyclizations of enynes in which the metal selectively activates the alkyne: an endocyclic process and two exo-cyclizations, one proceeding by anti attack of the alkene and a second one resulting in a syn addition. Although cyclobutenes may be formed in transition-metal-catalyzed cyclization of some enynes, particularly, 1,7-enynes, these compounds are not necessarily the intermediates in the skeletal rearrangement. Cyclobutenes are formed by ring expansion of syn-cyclopropyl metal-carbenes formed in the syn pathway.     

Regioselectivity of MAO-catalyzed allylmetallation of conjugated enynes with allylzirconiums

Various conjugated enynes 1 were subjected to the MAO-catalyzed reaction with the allylzirconium, generated by hydrozirconation of allenes. In light of the regiochemisty, the C---C bond formation occurs exclusively between the carbon of the allylzirconium and the “yne” part of the conjugated enyne 1. Steric demand of the -substituent X in 1 is the decisive factor for determing the the reactive site for 1.     

Density function studies on the PtCl2‐catalyzed asymmetric cycloisomerization reaction of hydroxylated enynes

The PtCl₂‐catalyzed asymmetric cycloisomerization reaction of hydroxylated enynes was studied using density functional theory (DFT). All structures have been optimized completely at the B3LYP/6‐311G(d,p) level. As shown, the cycloisomerization reaction is exothermic. The cycloisomerization reaction mainly undergoes the formation of catalyst‐hydroxylated enzyme coordination, the asymmetric cyclopropyl platinum carbene, catalyst–cyclopropyl enol coordination, and catalyst–cyclopropyl ketone coordination. The chirality‐limiting step for the asymmetric cycloisomerization reaction is the formation of the asymmetric cyclopropyl platinum carbene, and the rate‐determining step for this reaction is the formation of the catalyst–cyclopropyl ketone coordination. The dominant products predicted theoretically are (R,S) ‐syn_5a, in agreement with the experiment. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Chiral copper-bipyridine complexes: Synthesis, characterization and mechanistic studies on asymmetric cyclopropanation

Chiral bipyridine ligands of different steric properties when reacted with CuCl₂ formed orange, yellow or green solids of new copper(II) complexes, [Cu(L)Cl₂] (L = L2-6), in good yield. Together with [Cu(L1)Cl₂], these complexes were characterized in solution by UV-Vis spectroscopy and cyclic voltammetry. The complexes give d-d transitions between 860 and 970 nm, and exhibit one quasi-reversible Cu(II)/Cu(I) couple between +0.405 V and +0.516 V versus NHE. Two of the copper(II) complexes, [Cu(L5)Cl₂] and [Cu(L6)Cl₂], and a copper(I) complex of L1, [Cu(L1)Cl], were characterized by X-ray crystallography. The triflate derivatives of both the Cu(I) and Cu(II) complexes are active catalysts towards the cyclopropanation of ethyl diazoacetate with styrene. The asymmetric induction suffers when the size difference between the alkyl and alkoxyl groups was minimized. The mechanism of the cyclopropanation was studied with kinetic and competition experiments. The rate is first order in catalyst and ethyl diazoacetate, inverse order with styrene and is strongly affected by the counterion.     

Cobalt(I)-mediated cycloisomerization of enynes: mechanistic insights

[CpCo(CO)2] catalyzes the cycloisomerization of 1,n-enynes to afford selectively five- and six-membered ring systems in high yields. The factors governing the cyclization have been explored and we have discovered that the reaction associates two different, but complementary, reactivities of the cobalt(I) complexes. By a judicious choice of the substitution of the enyne, it was also possible to isolate a cyclobutene that arises from a cobaltcyclopentene     

trans-2,5-Dialkylpyrrolidinyl-containing phosphinamines. Synthetic and mechanistic studies in Pd-catalysed asymmetric allylic alkylation

The preparation of new phosphinamine ligands possessing an enantiopure trans-2,5-dialkylpyrrolidinyl unit linked by a rigid o-phenylene bridge to a diphenylphosphine is described. Only that route forming the trans-2,5-dialkylpyrrolidine in the final step from (2-aminophenyl)diphenylphosphine proved successful. The cyclocondensation proceeded in 48% and 27% yields, respectively, for the dimethyl- and diethyl-analogues. Their palladium complexes were prepared and applied to the test of enantioselective alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate in high chemical yields but with moderate enantioselectivities of up to 34% ee.¹H NMR spectra of the η³-allyl Pd complexes of four trans-2,5-dialkylpyrrolidine-containing ligands were analysed in an attempt to explain the results obtained. In the cases of the 1,3-diphenylallyl complexes, two diastereomers were observed for all four ligands and their configurations were assigned with the aid of COSY and NOESY experiments. The catalytic results obtained are best interpreted by the reaction proceeding with nucleophilic attack on the allyl trans to the phosphorus donor atom of the major diastereomer.     

Substituent effects on the Z/E-selectivity in cross-metathesis of conjugated enynes

Cross-metathesis of a range of conjugated enynes with alkenes turns out to proceed with preferential formation of Z-isomers over E-isomers up to >25:1. Careful studies including substrate modification and control experiments revealed that the reaction proceeds under kinetic rather than thermodynamic control. Driving forces for this substrate-dependent Z-selectivity are attributed to the steric hindrance between substituents on the reacting enynes and NHC ligand of the ruthenium catalyst in the putative metallacyclobutane, as well as chelation effects of suitably positioned functional groups to Ru, which is strongly supported by ab initio calculations.     

The reactions of trifluoromethyl and trichloromethyl radicals with conjugated and methylene-interrupted dienes and enynes

The photochemical addition of CF₃I to buta-1,3-diene and vinylacetylene in the gas phase gave 1,4-adducts as the main products. In gas phase reactions only products derived from hydrogen abstraction were detected in the CF₃I/penta-1,3-diene system, but the 1,4-adducts again predominated in the liquid phase. CCl₃Br similarly gave a mixture of 1,2- and 1,4-adducts, the latter predominating, on photochemical reaction with penta-1,3-diene. The 1,2-adduct was the main product from the CCl₃Br/pent-1-en-4-yn reaction, but some hydrogen abstraction was observed. The preference shown by conjugated dienes to give 1,4-adducts in the $\text{trans}$- configuration is interpreted in terms of steric factors and the propensity of dienes to adopt the $\text{s}$-$\text{trans}$ conformation.     

Isothiourea-mediated asymmetric O- to C-carboxyl transfer of oxazolyl carbonates: structure-selectivity profiles and mechanistic studies

The structural motif within a series of tetrahydropyrimidine-based isothioureas necessary for generating high asymmetric induction in the asymmetric Steglich rearrangement of oxazolyl carbonates is fully explored, with crossover and dynamic (19)F?NMR experiments used to develop a mechanistic understanding of this transformation.     

Catalytic asymmetric Pauson-Khand-type reactions of enynes with formaldehyde in aqueous media

The first example of an aqueous, asymmetric, and CO gas-free Pauson-Khand-type reaction is described. Using formaldehyde as a commercially available substitute for carbon monoxide, combined use of a hydrophilic phosphine (TPPTS) and a hydrophobic, chiral phosphine (tolBINAP) enable the reaction to proceed smoothly in aqueous media, even in the absence of carbon monoxide, and stereoselectively.     

Palladium-catalyzed hydrophosphinylation of alkenes and alkynes

Various palladium catalysts promote the addition of hypophosphorous derivatives ROP(O)H(2) to alkenes and alkynes in good yields and under mild conditions. Particularly, Cl(2)Pd(PPh(3))(2)/2 MeLi, and Pd(2)dba(3)/xantphos allow for phosphorus-carbon bond formation instead of transfer hydrogenation. Commercial aqueous solutions of hypophosphorous acid can be employed successfully at ambient temperature. With styrene and terminal alkynes, the regioselectivity (linear versus branched products) can be controlled to some extent with the catalytic system employed. The methodology considerably extends upon previous routes for the preparation of H-phosphinic acids and other organophosphorus compounds.