Rigby Group

Synthetic Interests of the Rigby Group

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This Page was Updated:
Friday, March 1, 2002

Development of Polymer-Supported Chromium Arene Complexes as Traceless Linkers for Solid-Phase Organic Synthesis

Current researcher: Chee-Seng, Lee

Solid phase synthesis has been used as an elegant way of quickly generating a diverse array of small molecules with minimal purification. Much of the effort has been focused on the development of traceless linkers. In this context, we proposed a selective and efficient method of loading p-arene chromium fragments onto a polystyrene resin.

Substitution a carbon monoxide ligand in chromium complex 1 by phosphinated polystyrene generated chromium polymeric complex 2 in high purity and good yield. Furthermore, we have been able to immobilize various arenes, and complete numerous synthetic transformations (Grignard reactions, reductions, acetylations, etc.). Finally, a simple decomplexation with iodine was utilized, which allows for the release of products 4 in good yields.

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Studies on the Asymmetric [6+4] Cycloaddition for the total Synthesis of Ingenol

Current researcher: Oliver Mirguet, Hoon Bae

Ingenol (1), the ester of which is a known tumor promoter isolated from the genus Euphorbia in 1968, still remains a formidable challenge to the synthetic organic community. We are currently investigating the total synthesis of this interesting diterpene. Our plan entails the use of an intramolecular [6+4] cycloaddition of diene-tropone 2 to construct the A, B and C rings of 1. This cycloaddition strategy not only forms two key C-C bonds, but also establishes three new stereocenters. Thus far, we have prepared tricycle 3 and elaborated it to the advanced intermediate 4 using novel reactions developed in our labs. Further studies have been initiated on an asymmetric version of the [6+4] cycloaddition reaction. Thus, an optically enriched tricycle 3 has been obtained. Intensive efforts are now being directed to elaborate intermediate 4 to ingenol (1).

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Bis(thioalkyl)carbenes: Insights into Structure, Properties and Synthetic Utility in Cycloadditions.

Current researcher: Nancy A. Neale

The synthetic utility of bis(thioalkyl)carbenes was previously demonstrated by workers in our laboratories. Thus, [1+4] cycloadditions between these thiocarbenes and vinyl isocyanates provided access to 5-membered heterocycles. Using Ab initio calculations (6-31g*), we have gathered insight into the structure and electronic properties of bis(thioalkyl)carbenes and the reason for their unexpected nucleophilic behavior.

Currently, our efforts are directed toward the use of this novel [1+4] cycloaddition for the total synthesis of homoerythrina alkaloid 8-oxoschelhammeridine (8). Thus, stirring carbene precursor 2 and vinyl isocyante 1 in refluxing benzene gives bicycle 3. Our plan for elaborating bicycle 3 to the core of the natural product involves a nucleophilic coupling with iodide 4 followed by a 7-exo-trig ring closure to give rise to either tetracycle 6 or 7. Further work will involve applying this methodlogy to the natural product 8.

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Development of a Chiral Catalyst for Cr(0) Higher-Order Cycloadditions

Current researcher: Will Kentish Barnes

The Cr(0) promoted higher-order cycloaddition reaction has provided a unique facile approach for the generation of medium-sized rings with a high degree of stereo and regio-selectivity. This type of cycloaddition has progressed in recent years; however, the potential for metal promoted asymmetric induction has remained relatively unexplored.

The development of a Cr(0) chiral catalyst for higher order cycloadditions is currently being investigated in our laboratories. We have found that optically active BINAP acts as a bidentate ligand to form L2Cr(CO)4 and L2Mo(CO)4 from C(CO)6 or Mo(CO)6. This work involves a study of the activation of these BINAP metal complexes by substitution of a carbon monoxide ligand with a more labile ligand. The ultimate goal will be the use of these chiral metal complexes for the use in catalytic asymmetric higher-order cyclizations.

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Studies of Addition of Aryl-halo and Aryl-methoxy Carbenes to Cyclohexene Isocyanates

Current researcher: Mona Aasmul

Our lab has observed a cycloaddition between cyclohexene isocyanates and aryl-substituted carbenes that is influenced by the nucleophilicity of the carbenes. Electrophilic carbenes (e.g. chloro-phenyl carbene) yield a [1+2] addition product (1) while an ambiphilic carbene (e.g. chloro-dimethoxyphenylcarbene) gives a mixture of compounds 1 and 2. We have developed nucleophilic carbenes, which provides primarily the [1+4] cycloadduct 2. We are currrently pursueing a synthesis of this alkaloid using these nucleophilic aryl-substituted carbenes for the total synthesis of Ningalin C (3) an marine alkaloid isolated from the Western Australian ascidian of the genus Didemnum or better known as a sea squirt.

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A Chromium Mediated [6+2+2] Cyclization Approach Toward the Total Synthesis of Pentelenic Acid

Current Researchers: Laxmisha Sridhar

Prior to our involvement in this project, studies toward the total synthesis of pentelenic acid (5) were undertaken by Charles Heap in our laboratories. He had successfully developed a route toward the advanced intermediate 4 of the triquinane 5. The method used to prepare 4 included a novel cyclization reaction whereby chromium complex 1 was photolyzed in the presence of the diyne 2 to give the pentacyclic compound 3 as a 1:1 mixture of diastereomers at the alcohol stereocenter (Note: six new stereocenters and four new rings are formed in a single reaction). Intermediate 3 was then elaborated to the advanced intermediate 4. Our research is directed toward preparing the optically active intermediate 4 and further elaborating it to the natural product 5.

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