Research in Organic Chemistry

Minehan Group

Researchin the Minehan group is primarily focused on the development of new syntheticmethods for carbon-carbon bond-formation, with an emphasis on the use ofenvironmentally friendly reagents and solvent systems. Inspiration for thedevelopment of these methods comes from the complex structures of naturallyoccurring substances of medicinal and pharmaceutical import. We are currentlypursuing three main lines of investigation:

1. The [3,3]-sigmatropic rearrangement of aliphaticallyl-alkynyl ethers is a relatively unexplored reaction in organic synthesis.Allyl-alkynyl ethers could be generated from allyl-1,1-dichlorovinyl ethers bytreatment with excess n-BuLi at low temperatures; However, subjecting allyl-dichlorovinylethers to these conditions, followed by quenching with an alcohol, leads torearranged products in the form of gamma, delta-unsaturated esters. Sigmatropicrearrangement is occurring rapidly and stereospecifically at low temperatures inthis process. Mechanistic investigations of this reaction are underway; theproposed ketene intermediate holds great synthetic promise, since it may beintercepted by a wide variety of nucleophiles to form an array of carbonylcompounds in a single step. We are also currently investigating alternativemethods for preparing allyl-alkynyl ether intermediates that avoid the use ofnucleophilic bases and toxic carbon tetrachloride.

2. Allylic substitution reactions are important and powerfulmethods for carbon-carbon bond-formation. Environmentally benign organoindiumreagents participate in transition-metal catalyzed cross-coupling reactions andallylic substitution reactions. We have recently discovered that 1-acetoxy-2,7-and 2,8-enynes undergo a palladium-catalyzed cyclization / substitutionreaction in the presence of organoindium reagents to form substituted 5- and6-membered carbo- and heterocycles. We envision that this process may beextended to the stereoselective synthesis of diverse fused 6-5 and 6-6 ringsystems. Since this process requires a stoichiometric amount of thetriorganoindium reagent, we are currently developing a more atom-efficientcyclization/substitution process employing aryl(dimethoxy)indium reagents

3. Allylindium reagents, generated in-situ from allyl halidesand indium metal, react with carbonyl compounds in water to form productscontaining a new carbon-carbon bond. We have prepared a series ofsilyl-substituted allylindium reagents that allow multiple carbon-carbon bondsto be formed in a single step in aqueous media upon reaction with appropriateelectrophiles. Such reagents may be employed in an environmentally benignpreparation of substituted pyrans and 7- and 8-membered carbocycles, which areat the core of a variety of biologically-important natural products.

Students in the Minehangroup gain practical experience in the synthesis, purification, andspectroscopic characterization of organic molecules. Some examples of theuseful skills obtained are:

1. Techniques for runningreactions under inert atmosphere

2. Purification of compounds by columnchromatography and radial chromatography

3. Analysis of reactions bythin-layer chromatography and GC-MS

4. Structure elucidation ofsynthetic compounds using NMR spectroscopy

Selected Recent Publications:

1. An Environmentally Benign Synthesis ofcis-2,6-Disubstituted Tetrahydropyrans via Indium-Mediated Tandem Allylation /Prins Cyclization Reaction. MinhPham, Amir Allatabakhsh, and Thomas Minehan. J. Org. Chem. 2008, inpress

2. Synthesis of Oxa-Bridged 7- and 8-Membered RingsVia Indium-Mediated Annulation of 1,4- and 1,5-Dicarbonyl Compounds with3-Iodo-2-[(trimethylsilyl)methyl]propene.Amir Allatabakhsh, Minh Pham, and Thomas Minehan. Heterocycles 2007, 72, 115-122.

3. Palladium-Catalyzed Reactions of Acetoxyenyneswith Triorganoindium Reagents. JohnT. Meza, Raffi A. Terzian and Thomas Minehan. Tetrahedron Lett. 2006, 47, 8905-8910.

4. Low-Temperature n-Butyllithium-InducedRearrangement of Allyl 1,1-Dichlorovinyl Ethers. Aaron Christopher, Dahniel Brandes, Stephen Kelly,and Thomas Minehan. Org. Lett., 2006, 8,451-454.

5. Synthesis of C-Aryl Glycopyranosides viaUncatalyzed Addition of Triarylindium Reagents to Glycals. Sarah Price, Stephen Edwards, Tiffany Wu and ThomasMinehan. Tetrahedron Lett. 2004, 45,5197-5201.

6. Efficient Palladium-Catalyzed NucleophilicAddition of Triorganoindium Reagents to Carbocyclic Derivatives. Lucas Baker and Thomas G. Minehan. J. Org. Chem. 2004, 69, 3957-3960.

7. Palladium-Mediated Cross-Coupling Reactions ofTrisdihydropyranylindium Compounds with Aryl Halides. Synthesis of C-Aryl Glycals. Ute Lehmann, Smita Awasthi, and Thomas G. Minehan. Org.Lett., 2003, 5,2405-2409.

A Selection of CurrentGroup Members.

From left: Bobby Salehani,Shayan Rab, Samuel Rodriguez-Torres, John Alec Moral, Armen Tudjarian, ThomasMinehan

Raffi Terzian and AmirAllatabakhsh present research posters at the 2006 CSUN 11^th AnnualStudent Research and Creative Works symposium

December 1, 2006