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P Andrew Evans

Publications and source records attributed to P Andrew Evans.

At least 19 recordsLinked to original sources
PubMed2005

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.

Alkynes↗
PubMed2005

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.

Journal Article↗
PubMed2004

Diastereoselective metal-catalyzed [4 + 2 + 2] carbocyclization reactions utilizing a rhodium N-heterocyclic carbene (NHC) complex: the first example of a rhodium NHC-catalyzed [m + n + o] carbocyclization.

The air and moisture stable rhodium N-heterocyclic carbene (NHC) complex, RhCl(IMes)(COD)(IMes =N,N[prime or minute]-bis(2,4,6-trimethylphenyl)imidazole-2-ylidine; COD = 1,5-cyclooctadiene), facilitates a diastereoselective metal-catalyzed [4 + 2 + 2] carbocyclization of 1,6-enynes in the presence of silver triflate and 1,3-butadiene.

Journal Article↗
PubMed2004

Diastereoselective intramolecular temporary silicon-tethered rhodium-catalyzed [4+2+2] cycloisomerization reactions: regiospecific incorporation of substituted 1,3-butadienes.

Transition metal-catalyzed carbocyclization reactions represent powerful methods for the construction of complex polycyclic systems. We have developed a regiospecific and diastereoselective intramolecular temporary silicon-tethered rhodium-catalyzed [4+2+2] cycloisomerization reaction of a tethered enyne for the construction of tricyclic eight-membered heterocycles and carbocycles. This methodology also allows (E)- and (Z)-olefins to be utilized in a stereospecific manner. The incorporation of either alkene geometry is particularly significant, since related carbocyclization reactions are often limited in this respect. Finally, the ability to utilize carbon-tethered 1,6-enynes and to regiospecifically incorporate substituted 1,3-butadiene derivatives provides exciting opportunities for future applications toward the total synthesis of cyclooctanoid containing diterpenes.

Journal Article↗
PubMed2004

Regio- and diastereoselective rhodium-catalyzed allylic substitution with acyclic alpha-alkoxy-substituted copper(I) enolates: stereodivergent approach to 2,3,6-trisubstituted dihydropyrans.

The regio- and diastereoselective transition metal-catalyzed allylic alkylation using alpha-heteroatom-substituted ketones and carboxylic acid derivatives represents a challenging and important synthetic transformation. We have developed a regio- and diastereoselective rhodium-catalyzed allylic alkylation reaction utilizing the copper(I) enolates derived from alkyl protected acyclic alpha-alkoxy aryl ketones. This study suggests that the ability to form a chelated enolate intermediate is crucial for obtaining high diastereoselectivity, whereas excellent regioselectivity is obtained regardless of the substituent. Hence, the excellent selectivity coupled with the synthetic utility of alpha-alkoxy aryl ketone enolates makes this an important new method for the construction of acyclic adjacent ternary stereogenic centers. Finally, the synthetic utility of this protocol was highlighted through the conversion of the aryl ketone to the ester and the development of a stereodivergent approach to 2,3,6-trisubstituted dihydropyrans relevant to target-directed synthesis.

Journal Article↗
PubMed2003

Enantioselective total synthesis of the potent antitumor agent (-)-mucocin using a temporary silicon-tethered ring-closing metathesis cross-coupling reaction.

The enantioselective total synthesis of the annonaceous acetogenin (-)-mucocin (1) was accomplished using a triply convergent 12-step sequence (longest linear sequence) in 13.6% overall yield. This represents the first application of the temporary silicon-tethered (TST) ring-closing metathesis (RCM) cross-coupling reaction and the enantioselective alkyne/aldehyde addition to the synthesis of a complex annonaceous acetogenin. Moreover, all three fragments required for the coupling reactions are conveniently prepared in 5-6 steps from two readily available enantiomerically enriched epoxides. Finally, this synthesis stimulated the development of a new approach for the construction of 3-hydroxy-2,6-disubstituted tetrahydropyrans, using the bismuth tribromide-mediated reductive etherification reaction, which represents a motif that is prevalent in a wide range of pharmacologically significant natural products.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Stereoselective construction of cis-2,6-disubstituted tetrahydropyrans via the reductive etherification of delta-trialkylsilyloxy substituted ketones: total synthesis of (-)-centrolobine.

[reaction: see text] The stereoselective intramolecular reductive etherification of delta-trialkylsilyloxy substituted ketones with catalytic bismuth tribromide and triethylsilane provides a convenient method for the construction of cis-2,6-disubstituted tetrahydropyrans. This method was highlighted in the key step of an expeditious total synthesis of the antibiotic, (-)-centrolobine.

Cyclization↗
PubMed2003

Stereoselective construction of cyclic ethers using a tandem two-component etherification: elucidation of the role of bismuth tribromide.

The stereodivergent construction of cyclic ethers remains an important area of synthetic interest, particularly given the ubiquity of C-glycoside derivatives in natural and unnatural pharmacologically important agents. This work describes a series of intramolecular etherification reactions of delta-trialkylsilyloxy aldehydes and ketones using catalytic bismuth tribromide and various trialkylsilyl nucleophiles for the construction of cis- and trans-2,6-di- and trisubstituted tetrahydropyrans. Furthermore, this study provides compelling evidence for the fact that the catalysis may be attributed to the hydrogen bromide and bismuth oxybromide derived from the hydrolysis of bismuth tribromide. The synthetic utility of this protocol is highlighted in the ability to construct adjacent tertiary ethers in a highly stereoselective manner and the development of a sequential two-component cross-coupling followed by reductive etherification process for the expeditious synthesis of nonadjacent tetrahydropyran rings.

Bismuth↗
PubMed2003

Regioselective and enantiospecific rhodium-catalyzed allylic alkylation reactions using copper(I) enolates: synthesis of (-)-sugiresinol dimethyl ether.

The transition metal-catalyzed allylic alkylation represents a fundamentally important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a regioselective and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical allylic alcohol derivatives using copper(I) enolates to prepare beta-substituted ketones. This protocol represents a convenient asymmetric Claisen rearrangement surrogate in which alpha-substituted enolates permit the introduction of an additional stereogenic center. The synthetic utility of this transformation was highlighted in the construction of a trans-1,2-disubstituted cyclohexene and the total synthesis of (-)-sugiresinol dimethyl ether. Finally, we anticipate that copper(I) enolates may prove useful nucleophiles in related metal-catalyzed reactions.

Alkylation↗
PubMed2003

Regio- and enantiospecific rhodium-catalyzed arylation of unsymmetrical fluorinated acyclic allylic carbonates: inversion of absolute configuration.

The transition metal-catalyzed allylic substitution with unstabilized carbon nucleophiles represents an important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a new regio- and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical chiral nonracemic allylic alcohol derivatives with aryl zinc bromides. This study demonstrates that the hydrotris(pyrazolyl)borate rhodium catalyst and zinc(II) halide salt are crucial for efficiency, while the addition of lithium bromide to the catalyst is necessary for obtaining optimal regiospecificity. The stereochemical course of this reaction was established through the synthesis of (S)-ibuprofen, which demonstrated that the alkylation proceeds with net inversion of absolute configuration consistent with direct addition of the nucleophile to the metal center followed by reductive elimination.

Alkylation↗