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.     

AlCl3-promoted highly regio- and diastereoselective [3 + 2] cycloadditions of activated cyclopropanes and aromatic aldehydes: construction of 2,5-diaryl-3,3,4-trisubstituted tetrahydrofurans

The AlCl(3)-catalyzed [3 + 2] cycloaddition reaction of diethyl trans-2,3-disubstituted cyclopropane-1,1-dicarboxylates and aromatic aldehydes was carried out under mild conditions to provide a series of diethyl 2,5-diaryl-4-benzoyltetrahydrofuran-3,3-dicarboxylates in moderate to good yields with excellent diastereoselectivities. While common 2,5-cis products were obtained with electron-neutral or electron-poor aryl aldehydes, the much less common 2,5-trans products were obtained in excellent diastereoselectivities when electron-rich aryl aldehydes were used. The relative configurations of those typical products were confirmed by X-ray crystallographic analyses.     

Highly regio- and diastereoselective construction of spirocyclopenteneoxindoles through phosphine-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman carbonates with isatylidene malononitriles

Phosphine-catalyzed highly regio- and diastereoselective [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with isatylidene malononitriles has been disclosed to give the corresponding spirocyclopenteneoxindoles in excellent yields under mild conditions. A plausible reaction mechanism has also been proposed on the basis of previous literature.     

Regio- and enantioselective intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with methyl arylpropiolates

Transition metal-catalyzed [m+n+o] carbocyclization reactions provide powerful methods for the construction of complex polycyclic systems that are generally not accessible through classical pericyclic reactions. We have developed the first regio- and enantioselective crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon- and heteroatom-tethered 1,6-enynes with unsymmetrical 1,2-disubstituted alkynes. This study clearly delineates the ligand requirements for obtaining excellent regio- and enantioselectivity. Furthermore, the ability to utilize various electron-withdrawing groups, and to introduce quaternary carbon stereogenic centers, provides the level of versatility necessary for its application to target-directed synthesis. Additional studies on the development and application of this novel methodology to the total synthesis of natural products are currently underway.     

Highly regio- and diastereoselective anionic [3 + 2] cycloaddition under phase transfer catalytic conditions

A highly trans and regioselective anionic formal [3 + 2] cycloaddition was achieved with allylic sulfones having an MBH acrylamide backbone under phase transfer organocatalytic conditions giving rise to the formation of unprecedented densely substituted cyclopentene derivatives.     

Rhodium-catalyzed chemo-, regio-, and enantioselective [2 + 2 + 2] cycloaddition of alkynes with isocyanates

[reaction: see text] We have developed a cationic rhodium(I)/modified-BINAP complex-catalyzed chemoselective [2 + 2 + 2] cycloaddition of alkynes with isocyanates leading to a wide range of 2-pyridones. This method was successfully applied to the chemo-, regio-, and enantioselective synthesis of axially chiral 2-pyridones from unsymmetrical alpha,omega-diynes, bearing an ortho-substituted phenyl at one terminal position, and alkyl isocyanates.     

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.     

Electrooxidative palladium- and enantioselective rhodium-catalyzed [3 + 2] spiroannulations

Despite indisputable progress in the development of electrochemical transformations, electrocatalytic annulations for the synthesis of biologically relevant three-dimensional spirocyclic compounds has as of yet not been accomplished. In sharp contrast, herein, we describe the palladaelectro-catalyzed C–H activation/[3 + 2] spiroannulation of alkynes by 1-aryl-2-naphthols. Likewise, a cationic rhodium(iii) catalyst was shown to enable electrooxidative [3 + 2] spiroannulations via formal C(sp³)–H activations. The versatile spiroannulations featured a broad substrate scope, employing electricity as a green oxidant in lieu of stoichiometric chemical oxidants under mild conditions. An array of spirocyclic enones and diverse spiropyrazolones, bearing all-carbon quaternary stereogenic centers were thereby accessed in a user-friendly undivided cell setup, with molecular hydrogen as the sole byproduct.

Despite indisputable progress in the development of electrochemical transformations, electrocatalytic annulations for the synthesis of biologically relevant three-dimensional spirocyclic compounds has as of yet not been accomplished.     

Rh-catalyzed [4 + 2] carbocyclization of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols

Regio-, diastereo-, and enantioselective intermolecular [4 + 2] carbocyclizations of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols have been developed by using a cationic rhodium(I)/dppb or dppp complex as a catalyst.     

Diastereoselective intermolecular rhodium-catalyzed [4 + 2 + 2] carbocyclization reactions: computational and experimental evidence for the intermediacy of an alternative metallacycle intermediate

Intermolecular rhodium-catalyzed [m + n + o] reactions of 1,6-enynes and various pi-components (carbon monoxide, alkynes, 1,3-butadienes, etc.) provide an expeditious approach for the construction of polycyclic fragments that represent important synthons for target-directed synthesis. We present computational and experimental evidence for the existence of a previously undescribed reaction pathway for the rhodium-catalyzed [4 + 2 + 2] reaction involving a 1,6-enyne. This model clearly demonstrates the origin of the excellent diastereoselectivity in this type of reaction and the remarkable tolerance of both (E)- and (Z)-isomers within the 1,6-enyne, which is generally prone to competitive ene-cycloisomerization.     

Triptycenediols by rhodium-catalyzed [2+2+2] cycloaddition

An efficient, modular synthesis of triptycene derivatives is presented, in which the triptycene ring system is constructed from readily available anthraquinone and alkyne starting materials. A rhodium-catalyzed alkyne cyclotrimerization reaction serves as the key step in this new method for the preparation of these useful unnatural products.     

First practical synthesis of 2- or 3-fluoroalkylated indenols via cobalt-catalyzed [2 + 3] carbocyclization of fluorine-containing alkynes and 2-iodoaryl ketones

[2 + 3] Cycloaddition reaction of fluorine-containing alkynes with various 2-iodoaryl ketones in the presence of CoCl₂(dppf) catalyst proceeded very smoothly to give the corresponding 2- or 3-fluoroalkylated indenols in 57–98% yields. These regioisomers could be successfully separated and obtained in a pure form. From X-ray crystallographic and NOESY analyses, major or minor regioisomers were determined as 3- or 2-fluoroalkylated indenols, respectively.     

Thermal intramolecular cycloaddition of 4-alkenylfulvene; highly regio- and diastereoselective formation of [4+2] adduct

4-Alkenylfulvenes were prepared by the annulation of 1,4-ynediones and allylidenetriphenylphosphorane and subjected to a thermal reaction. Highly regio- and stereoselective [4+2] cycloaddition is accomplished with 4-((R)-3-benzyloxypent-4-en-1-yl)fulvene and the resulting adduct is transformed into bicyclo[3.3.0]octene derivative.     

Nickel-catalyzed intermolecular [3 + 2 + 2] cocyclization of ethyl cyclopropylideneacetate and alkynes

The [3 + 2 + 2] cocyclization of ethyl cyclopropylideneacetate (1a) and terminal alkynes (2) proceeded smoothly in the presence of 10 mol % "Ni(PPh3)2", which was prepared in situ from Ni(cod)2 and PPh3. The high reactivity of 1a, which was induced by the introduction of an electron-withdrawing group, is very important for the progress of this reaction. The cycloheptadiene derivatives were synthesized in highly selective manner in good yields.     

Enantioselective synthesis of indolizidines bearing quaternary substituted stereocenters via rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and terminal alkynes

An enantioselective synthesis of indolizidines bearing quaternary substituted stereocenters by way of a rhodium-catalyzed [2+2+2] cycloaddition of substituted alkenyl isocyanates and terminal alkynes is described. The reaction provides lactam products using aliphatic alkynes, whereas aryl alkynes give rise to vinylogous amide products. Through modification of the phosphoramidite ligand, high levels of enantioselectivity, regioselectivity, and product selectivity are obtained for both products.     

Enantioselective rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and terminal alkynes: application to the total synthesis of (+)-lasubine II

The use of TADDOL-based phosphoramidite ligands on rhodium allows for the incorporation of terminal alkynes in the [2+2+2] cycloaddition with alkenyl isocyanates. Terminal aliphatic alkynes provide bicyclic lactams, while the use of aryl alkynes provides complementary access to vinylogous amides. Product selectivity seems to be governed by a combination of electronics and sterics, with smaller and/or more electron-deficient substituents favoring lactam formation. The use of homologous alkenyl isocyanates leads to an expedient asymmetric total synthesis of the alkaloid lasubine II.     

A novel and diastereoselective construction of H-pyrazolo[3,2-a]isoquinoline fused spirooxindoles via [3+2] cycloaddition

A one-pot, highly efficient and diastereoselective construction of 1,2-dihyro-10′bH-spiro[indole-3,1′-pyrazole[3,2-a]isoquinoline]-2′-carboxylates via silver triflate-catalyzed [3+2] cycloaddition of N′-(2–alkynylbenzylidene)hydrazide with methyleneindolinones in good to excellent yield has been described. The transformation involves initially a condensation followed by 6-endo-intramolecular cyclization forming dipole which then undergoes [3+2]-cycloaddition with methyleneindolinones and finally, β-hydrogen elimination.