Origins of stereoselectivity in the oxido-alkylidenation of alkynes

A mild, convenient oxido-alkylidenation of alkynes is described. The three-step sequence involves the 1,3-dipolar cycloaddition of a nitrone and an alkynoate, oxidation of the resulting isoxazoline, and stereoselective extrusion of nitrosomethane. Quantum mechanical calculations identified the interactions of R3 with the oxidant and the preferred conformation of a diradical intermediate as major factors controlling the stereoselectivity of the oxidation and torquoselectivity of the extrusion.     

On the origin of regio- and stereoselectivity in the rhodium-catalyzed vinylarenes hydroboration reaction

We studied the hydroboration of vinylarenes using rhodium complexes bearing atropoisomeric ligands. For the first time, an NMR spectroscopy study of the styrene and catecholborane addition to the precursor of catalyst [Rh(COD)(L-L)]BF(4), where L-L = (R)-BINAP and (R)-QUINAP, showed evidence of the structure of intermediates involved in the catalytic cycle. On the basis of this evidence, and using DFT calculations and QM/MM strategies, we investigated the origin of regio- and stereoselectivity. We determined the structure and stability of the key intermediates for several ligands and substrates and found excellent agreement between the relative stability of the intermediates and the experimentally observed trends. Using model systems, we analyzed the role of the steric and electronic features of the ligands and the substrates in detail.     

Synthesis of isochromene and related derivatives by rhodium-catalyzed oxidative coupling of benzyl and allyl alcohols with alkynes

The straightforward synthesis of isochromene derivatives and related cyclic ethers is achieved by the rhodium-catalyzed oxidative coupling of α,α-disubstituted benzyl and allyl alcohols with alkynes. The hydroxy groups effectively act as the key function for the regioselective C-H bond cleavage.     

Enantioselective synthesis of axially chiral biaryls through rhodium-catalyzed complete intermolecular cross-cyclotrimerization of internal alkynes

[reaction: see text] We have developed a cationic rhodium(I)/H8-BINAP complex-catalyzed complete intermolecular cross-cyclotrimerization of internal alkynes with dialkyl acetylenedicarboxylates. This reaction was successfully applied to enantioselective synthesis of axially chiral biaryls utilizing internal alkynes bearing ortho-substituted phenyl and acetoxymethyl in each terminal position. The axial chirality is constructed at the formation of benzene rings with high enantioselectivity (up to 96% ee).     

Synthesis of highly substituted acenes through rhodium-catalyzed oxidative coupling of arylboron reagents with alkynes

The rhodium-catalyzed oxidative 1:2 coupling reactions of arylboronic acids or their esters with alkynes smoothly proceed to produce the corresponding annulated products. Of special note, highly substituted, readily soluble, and tractable anthracene and tetracene derivatives can be obtained selectively from 2-naphthyl- and 2-anthrylboron reagents, respectively.     

Highly enantioselective direct reductive coupling of conjugated alkynes and alpha-ketoesters via rhodium-catalyzed asymmetric hydrogenation

Catalytic hydrogenation of 1,3-enynes 1a-7a in the presence of ethyl pyruvate and related activated ketones using chirally modified cationic rhodium catalysts results in reductive coupling to afford dienylated alpha-hydroxy esters 1b-7b and 3c-3f with exceptional levels of regio- and enantiocontrol. These studies represent the first highly enantioselective direct catalytic reductive couplings of alkynes to ketones. As illustrated by the conversion of 6b to 6c-6h, the diene containing the side chain of the coupling products is subject to diverse chemo- and regioselective manipulation. Reductive coupling of enyne 6a and ethyl pyruvate using elemental deuterium provides the monodeuterated product deuterio-6b, consistent with a catalytic mechanism involving alkyne-carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle, as corroborated by ESI-MS analysis.     

Redox-neutral atom-economic rhodium-catalyzed coupling of terminal alkynes with carboxylic acids toward branched allylic esters

A new method for the preparation of a wide range of branched allylic esters from terminal alkynes that proceeds via a redox-neutral propargylic CH activation employing a rhodium(I)/DPEphos catalyst is reported.     

The ground-state average structure of methyl isocyanide

The use of recently determined highly precise inertial data for various isotopic modifications of methyl isocyanide has enabled the ground-state average, or r_z, structure to be determined to within very narrow limits. Harmonic corrections to ground-state rotational constants have been calculated using a high-quality, experimentally determined harmonic force field. The derived zero-point inertial constants are sufficiently accurate to enable changes in the CH bond length and NCH bond angle on deuteration to be determined. The present r_z structure determination is believed to be a physically realistic estimate of the ground-state average geometry of methyl isocyanide.     

Ligand effects in the rhodium-catalyzed addition of alkynes to aldehydes and diketones. Modification of the β-diketonate ligand

A catalytic amount of dicarbonylacetonato rhodium(I) and a phosphine ligand bearing bulky electron-donating alkyl groups has been shown to generate an effective catalyst for the addition of alkynes to aldehydes and activated ketones under mild, neutral conditions. While previous studies have shown that modification of the phosphine has significant effects on the activity of the catalyst, the role of the β-diketonate ligand has not been probed. Six different β-diketonate rhodium complexes were synthesized and their ability to catalyze the alkyne addition reaction was evaluated. Changing the structure of the β-diketonate ligand can have a noticeable effect on the reaction rate. Acetylacetonate derivatives with strong electron withdrawing groups have a detrimental effect on the catalytic activity, while bulky and electron rich β-diketonate derivatives provide more efficient catalysts.     

Regio- and stereoselective synthesis of alkenylphosphines: a rhodium-catalyzed hydrophosphination of alkynes using a silylphosphine

A novel rhodium-catalyzed hydrophosphination of alkynes using a silylphosphine as a phosphino group source is described. A variety of alkynes, both terminal and internal ones with aryl, alkyl, and carboxyl groups, gave the corresponding alkenylphosphines in a highly regioselective and syn-selective manner. Alkenes with an electron-withdrawing group also gave the corresponding adducts in good yields.     

A study on the regio- and stereoselectivity in palladium-catalyzed cyclizations of alkenes and alkynes bearing bromoaryl and nucleophilic groups

We have studied the remarkable dependence of the stereochemistry of the cyclization on the double bond geometry and of the effect of the bulkiness of the nucleophile on the regiochemistry of the palladium mediated cyclization of alkenes bearing aryl bromides and nucleophiles. In contrast, the cyclization of the acetylenic homologous substrates is not dependent on the nature of the nucleophile.     

Enantioselective reductive coupling of alkynes and alpha-keto aldehydes via rhodium-catalyzed hydrogenation: an approach to bryostatin substructures

[STRUCTURE: SEE TEXT] Hydrogen-mediated reductive coupling of glyoxal 2 and 1,3-enyne 3 provides alpha-hydroxy ketone 4 in 70% yield and 91% enantiomeric excess. Notably, the benzylic ether and diene side chain of 4 remain intact under the conditions of hydrogen-mediated coupling. In four steps, alpha-hydroxy ketone 4 is converted to pyrans 8 and 9, which embody key structural features of the bryostatin recognition domain.     

Reactivity of cyclopalladated compounds derived from biphenyl-2-ylamine towards carbon monoxide, butyl isocyanide and alkynes

The reactivity of the dimeric cyclopalladated compounds derived from biphenyl-2-ylamine (μ-X)₂[κ²-N2′,C1-1-Pd-2-{(2′-NH₂C₆H₄)C₆H₄}]₂ [X = OAc (1), X = Cl (2)] towards unsaturated organic molecules is reported. Compound 1 reacted with carbon monoxide and ^tbutyl isocyanide producing phenanthridin-6(5H)-one and N-tert-butylphenanthridin-6-amine in 63% and 88% yield, respectively. Compound 2 reacted separately with diphenylacetylene and 3-hexyne, affording the mononuclear organopalladium compounds [κ²-N2″,C1-η²-C2,C3- 1-Pd{(R-CC-R)₂-2′-(2″-NH₂C₆H₄)C₆H₄}Cl] [R = Ph (5), R = Et (6)] in 50-60% yield, which derived from the insertion of two alkyne molecules into the C-Pd σ bonds of 2. The crystal structure of compounds 5 and 6 has been determined. Compound 5 crystallized in the monoclinic space group P2₁/n with a = 13.3290(10) Å, b = 10.6610(10) Å and c = 22.3930(10) Å and β = 100.2690(10)°. Compound 6 crystallized in the triclinic space group with a = 7.271(7) Å, b = 10.038(3) Å and c = 16.012(5) Å, and α = 106.79(3)°, β = 96.25(4)° and γ = 99.62(4)°. The crystal structures of 5 and 6 have short intermolecular Pd-Cl?H-N-Pd non-conventional hydrogen bonds, which associated the molecules in chains in the first case and in dimers in the second.     

Regioselective rhodium-catalyzed intermolecular [2+2+2] cycloaddition of alkynes and isocyanates to form pyridones

A highly regioselective rhodium-catalyzed intermolecular [2+2+2] cycloaddition of terminal alkynes with a variety of isocyanates to provide 2- and 4-pyridones has been developed. This reaction proceeds in good to excellent yields and overcomes the problem of dimerization and trimerization through the use of phosphoramidite ligands. A CO migration in the metallacycle is proposed to account for the formation of 4-pyridone.     

Intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with symmetrical and unsymmetrical alkynes

The crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon and heteroatom tethered 1,6-enynes can be accomplished with symmetrical and unsymmetrical alkynes, to afford the corresponding bicyclohexadienes in an efficient and highly selective manner.     

Asymmetric Michael addition of a recyclable chiral amine: inversion of stereoselectivity caused by the difference of ethereal solvents

The Michael addition of a chiral amine [(-)- 6] to alpha,beta-unsaturated esters ( 4) was attained and the stereoselectivity was inverted by changing the solvent from diethyl ether to tetrahydrofuran when alpha,beta-unsaturated esters having an aromatic ring at the beta-position were employed. In addition, the chiral auxiliary in the Michael adducts ( 9A) was facilely removed with N-iodosuccinimide to afford beta-amino esters ( 10A) and 2-methoxy- d-bornylaldehyde ( 11), which can be reclaimed to the chiral amine ( 6) by reductive amination.     

A density functional theory study of rhodium-catalyzed hetero-[5+2]-cycloaddition of cyclopropyl imine derivatives and alkynes

The intermolecular [5+2]-cycloaddition mechanism of cyclopropyl imines and alkynes catalyzed by [Rh(CO)2Cl]2 has been studied using density functional theory, comparing this multistep process with the two-step reaction in the absence of catalyst. Calculations show that a similar mechanism to that found for dihydroazepines could also lead to the formation of oxepines by replacing the imine nitrogen by oxygen. The results indicate that the formation of the oxepine can proceed with smaller barriers than those found for dihydroazepines. In fact, energy barriers are even smaller than those for other reactions employed for oxepine production, exhibiting values similar to those obtained for the reactions between acetilene and vinylcyclopropanes. Several substituted alkynes were tested for the reaction leading to no significant differences among them.