Synthetic Organic Chemistry, Natural Products

Our main interest is synthetic organic chemistry. Research in our laboratory focuses on four major areas. These are (1) new synthetic methodology, (2), asymmetric synthesis (3) natural product synthesis, and (4) new materials. The development of new methods for the preparation of enantiomerically pure compounds is an area of intense scrutiny. In this context, the design and execution of transformations which utilize catalytic amounts of chiral Lewis acids to install chirality in prochiral substrates has become very important. A program of high priority in our group is the development of synthetically useful radical reactions, especially, enantioselective variants using chiral Lewis acid catalysis. The stereoselectivity in these reactions will be established by manipulating the geometry of the reactive complex by judicious choice of simple, readily available, and easily removable achiral templates, ligands, and Lewis acids. We have recently demonstrated that high enantioselectivity can be achieved in conjugate addition of carbon radicals, amines, and carbanions to α,β-unsaturated carboxyl derivatives using catalytic amounts chiral Lewis acids. A better understanding of these reactions, their refinement, and extension to other bond forming processes are projects under investigation.

A Model for Explaining the Stereochemical Outcome in Conjugate Radical Additions to Functionalized α-Methylacrylates

Total synthesis of several biologically active terpene and alkaloid natural products are being pursued in our laboratory. These have a symbiotic relationship with other programs in the group which involve the development of methods for achieving high levels of stereochemical control. Other ongoing projects include the utilization of agricultural materials as feed stocks for the generation of commercially useful materials, synthesis of conducting polymers, and development of sensors for the estimation of corrosion.

Selected Publications

Enantioselective Synthesis of β-Amino Acid Derivatives. Conjugate Addition of O-Substituted Hydroxylamines to Enamides. Sibi, M. P.; Liu, M.; Shay, J. J. J. Org. Chem. 2003, 68, 0000.

Chiral Relay: A Novel Strategy for the Control and Amplification of Enantioselectivity in Chiral Lewis Acid Promoted Reactions. Corminboeuf, O.; Quaranta, L.; Renaud, P.; Liu, M.; Jasperse, C. P.; Sibi, M. P. Chem. Eur. J. 2003, 9, 28-35.

Determination of Corrosion on Aluminum Alloy under Protective Coatings Using Fluorescent Probes. Sibi, M. P.; Zong, Z. Progress in Organic Coatings 2003, 47, 8-15.

Radical-Mediated Annulation Reactions. Rheault, T. R.; Sibi, M. P. Synthesis 2003, 803-819.

Synthesis of Oxacycles by Tandem Radical Addition-Cyclization Reactions. Sibi, M. P.; Patil, K.; Rheault, T. R. Eur. J. Org. Chem. 2003, 0000.

Enantioselective Radical Reactions. Sibi, M. P.; Manyem. S.; Zimmerman, J. Chem. Rev. 2003, 103, 3263-3296.

Enantioselective Radical Conjugate Addition. A New Methodology for the Synthesis of Acetate Aldols. Sibi, M. P.; Zimmerman, J.; Rheault, T. R. Angew. Chem. Int. Ed. 2003, 42, 0000. VIP article,

b-Heteroatom-substituted Alkanamides. Sibi, M. P.; Manyem, S. Chapter 21.7, Science of Synthesis, Weinreb, S. M. Ed.; Georg Thieme Verlag: Stuttgart, 2004. Invited Article (Manuscript under preparation)

Commentary on "Tin-Free Radical-Mediated C–C-Bond Formations. S. Kim, C. J. Lim, S.-E. Song and H.-Y. Kang, Chem. Commun., 2001, 1410–1411; S. Kim, H.-J. Song, T.-L. Choi and J.-Y. Yoon, Angew. Chem. Int. Ed. 2001, 40, 2524-2526; S. Kim and C. J. Lim, Angew. Chem. Int. Ed. 2002, 41, 3265-3267."

Manyem, S.; Zimmerman, J.; Patil, K.; Sibi, M. P. Chemtracts 2003, 16, 0000. Invited Article

Commentary on "Enantioselective Synthesis without Discrete Optically Active Additives. Singleton, D. A.; Vo, L. K. J. Am. Chem. Soc. 2002, 124, 10010-10011" Sibi, M. P.; Manyem, S. Chemtracts 2003, 16, 0000.

A New Class of Modular Chiral Ligands with Fluxional Groups. Sibi, M. P.; Zhang, R.; Manyem. S. J. Am. Chem. Soc. 2003, 125, 9306-9307.

Enantioselective Synthesis of α,β-Disubstituted-β-Amino Acids. Sibi, M. P.; Prabagaran, N.; Ghorpade, S. G.; Jasperse, C. P. J. Am. Chem. Soc. 2003, 125, 0000.

Tandem radical reactions and ring-closing metathesis. Application in the synthesis of cyclooctenes. Sibi, M. P.; Aasmul, M.; Hasegawa, H.; Subramanian, T. Org. Lett. 2003, 5, 2883-2886.

Enantioselective Radical Reactions. The Use of Metal Triflimides as Lewis Acids. Sibi, M. P.; Petrovic, G. Tetrahedron: Asymmetry, 2003, 15, ASAP article.

Enantioselective Radical Allylation Reactions using Chiral Lanthanide Lewis Acids. Sibi, M. P.; Manyem, S.; Subramaniam, R. Tetrahedron, 2003, 59, 0000.

Recent Advances in the Stereoselective Synthesis of β-Amino Acids. Liu, M.; Sibi, M. P. Tetrahedron 2002, 58, 7991-8035.

Temperature Dependent Reversal of Stereochemistry in Enantioselective Conjugate Amine Additions. Sibi, M. P.; Gorikunti, U.; Liu, M. Tetrahedron 2002, 58, 8357-8363.

Enantioselective Conjugate Addition of Silylketene Acetals to Enamidomalonates. Synthesis of b-Amino Acid Derivatives. Sibi, M. P.; Chen, J. Org. Lett. 2002, 4, 2933-2936.

Free Radical Mediated Conjugate Additions. Enantioselective Synthesis of (-)-Enterolactone, (-)-Arctigenin, (-)-Isoarctigenin, (-)-Nephrosetranic Acid and (-)-Roccellaric Acid. Sibi, M. P.; Liu, P.; Ji, J.; Hajra, S.; Chen, J. J. Org. Chem. 2002, 67, 1738-1745.

Acyclic Diastereoselection in Prochiral Radical Addition to Prochiral Olefins. Sibi, M. P.; Rheault, T. R.; Chandramouli, S. V.; Jasperse, C. P. J. Am. Chem. Soc. 2002, 124, 2924-2930.

The Role of the Achiral Template in Enantioselective Transformations. Radical Conjugate Additions to a-Methylacrylates Followed by Hydrogen Atom Transfer. Sibi, M. P.; Sausker, J. B. J. Am. Chem. Soc. 2002, 124, 984-991.

Enantioselective Conjugate Addition of Hydroxylamines to Pyrazolidinone Acrylamides. Sibi, M. P.; Liu, M. Org. Lett. 2001, 3, 4181-4184.

Radical-Mediated Annulation Reactions. A Versatile Strategy for the Preparation of a Series of Carbocycles. Sibi, M. P.; Chen, J.; Rheault, T. R. Org. Lett. 2001, 3, 3679-3681.

Highly Diastereoselective Radical Addition-Cyclization Strategy: Facile Synthesis of Substituted Furans. Sibi, M. P.; Rheault, T. R.; Miyabe, H.; Patil, K.; Jasperse, C. P. C. R. Acad. Sci. Ser II C 2001, 4, 581-584.

Radical Reactions in Combinatorial Chemistry. Ganesan. A.; Sibi, M. P. in Handbook for Combinatorial Chemistry, Golitz, P., Nicolaou, K. C.; Eds.; Wiley-VCH, Weinheim, 2001.

Enantioselective Conjugate Addition of Organo-magnesium Amides to Enamidomalonates. Synthesis of Either Enantiomer of b-Amino Acid Derivatives. Sibi, M. P.; Asano, Y. J. Am. Chem. Soc. 2001, 123, 9708-9709.

Enantioselective Tandem Radical Reactions. Vicinal Difunctionalization in Acyclic Systems with Control over Relative and Absolute Stereochemistry. Sibi, M. P.; Chen, J. J. Am. Chem. Soc. 2001, 123, 9472-9473.

A New Approach to Enantiocontrol and Enantioselectivity Amplification. Chiral Relay in Diels-Alder Reactions. Sibi, M. P.; Venkatraman, L.; Liu, M.; Jasperse, C. P. J. Am. Chem. Soc. 2001, 123, 8444-8445

Reversal of Stereochemistry in Enantioselective Transformations. Can they be Planned or are they just Accidental. Sibi, M. P.; Liu, M. Cur. Org. Chem. 2001, 5, 719-755.

Enantioselective H-Atom Transfer Reactions. Synthesis of α-Amino Acids. Sibi, M. P.; Asano, Y.; Sausker, J. Angew. Chem. Int. Ed. 2001, 40, 1293-1296.

Enantioselective Synthesis of Peperomins A-D and Analog. Examination of Diastereoselective Cuprate Conjugate Additions to Enoyl Oxazolidinones. Sibi, M. P.; Johnson, M. D.; Punniyamurthy, T. Can. J. Chem. 2001, 79, 1546-1555.

Enantioselective Radical Reactions. Sibi, M. P.; Rheault, T. R. In Radicals in Organic Synthesis, Renaud, P. and Sibi, M. P., Eds, Wiley-VCH, 2001.

Chiral Lewis Acid Catalyzed Conjugate Addition of N-benzylhydroxylamine to β-Aryl Enoates. Enantioselective Synthesis of b-Amino Acid Precursors. Sibi, M. P.; Liu, M. Org. Lett. 2000, 2, 3393-3396.

Enantioselective Conjugate Additions. Sibi, M. P.; Manyem, S. Tetrahedron 2000, 56, 8033-8061.

Higher Selectivity at Higher Temperatures! Effect of Precursor Stereochemistry on Diastereoselectivity in Radical Allylations. Insight into the Role of the Lewis Acid. Sibi, M. P.; Rheault, T. R. J. Am. Chem. Soc. 2000, 122, 8873-8879.

Enantioselective Synthesis of cis-N-Carbobenzyloxy-3-Hydroxyproline Ethylester. Sibi, M. P.; Christensen, J. W. in Catalysts for the Fine Chemical Industry Roberts, S. M., Ed., Wiley, Oxford, 2000.

Copper Lewis Acids in Organic Synthesis. Sibi, M. P.; Cook, G. R. in Handbook of Lewis Acids, Yamamoto, H., Ed., Wiley-VCH, 2000.

Enantioselective Reduction of Ketones using Oxazaborolidines. Sibi, M. P.; Liu, P.; Cook, G.R. in Catalysts for the Fine Chemical Industry Roberts, S. M., Ed., Wiley, Oxford, 2000.

A New Methodology for the Synthesis of β-Amino Acids. Sibi, M. P.; Deshpande, P. K. J. Chem. Soc. Perkin Trans1 2000, 1461-1466.

Stereoselective Radical Reactions. Sibi, M. P.; Ternes, T. R. in Modern Carbonyl Chemistry, Otera, J., Ed, Wiley-VCH, 2000 pp 507-538.

A Short Synthesis of Both Enantiomers of Enterolactone. Sibi, M. P.; Liu, P.; Johnson, M. D. Can. J. Chem. 2000, 78, 133-139.

Patents

1. Method for Preparation of Optically Active Diarylalanines. Sibi, M. P.; Deshpande, P. K.; La Loggia, A. J. US Patent 5623087

2. A New Catalytic Process for the Conversion of Olefins to Carboxylic Acids. Sibi, M. P.; Boudjouk, P.; Ji, J. US Patent 5596111.

3. Diarylaminoprpopanediol and Diarylmethyloxazolidninone Compounds. Sibi, M. P.; Deshpande, P. K.; La Loggia, A. J. US Patent 5939554. Issued 8/17/1999

4. A New Method for the Preparation of Carboxylic Acids. Sibi, M. P.; Boudjouk, P.; Ji, J. US Patent 5939572. Issued 8/17/1999

5. New Catalytic Methods for the Synthesis of Optically Active β-Amino Acids. Sibi, M. P.; Shay, J. J.; Liu, M.; Jasperse, C. P. US Patent 6080857. Issued 6/27/2000