Asymmetric Catalysis of the Transannular Diels-Alder Reaction

Transannular chemical reactions are unparalleled in their ability to generate high degrees of stereochemical and architectural complexity in a single transformation. However, the successful application of this approach in synthesis depends on the ability to predict and control the outcome of the transannular reaction. Use of a chiral catalyst in this context represents an attractive, yet unused, strategy. This report describes a catalytic, asymmetric transannnular Diels-Alder (TADA) reaction that affords polycyclic products in high enantiomeric excess. This catalyst system can also alter the inherent diastereoselectivity of cyclizations with substrates containing chiral centers. Additionally, the catalytic enantioselective TADA has been used as the key step in a total synthesis of the sesquiterpene 11,12-diacetoxydrimane; this route may provide a general approach to the polycyclic carbon framework shared by many terpene natural products.

[1]  C. Fehr,et al.  Enantioselective intramolecular aldol addition/dehydration reaction of a macrocyclic diketone: synthesis of the musk odorants (R)-muscone and (R,Z)-5-muscenone. , 2007, Angewandte Chemie.

[2]  G. Breault,et al.  The temporary silicon connection in the control of the regiochemistry of 4 + 2 cycloadditions , 1992 .

[3]  E. Corey,et al.  Asymmetric Diels-Alder reactions catalyzed by a triflic acid activated chiral oxazaborolidine. , 2002, Journal of the American Chemical Society.

[4]  Takaaki Sato,et al.  Total synthesis and bioactivity of an unnatural enantiomer of merrilactone a: development of an enantioselective desymmetrization strategy. , 2007, The Journal of organic chemistry.

[5]  K. Tamao,et al.  (Diisopropoxymethylsilyl)methyl Grignard reagent: a new, practically useful nucleophilic hydroxymethylating agent , 1983 .

[6]  E. Corey,et al.  Triflimide activation of a chiral oxazaborolidine leads to a more general catalytic system for enantioselective Diels-Alder addition. , 2003, Journal of the American Chemical Society.

[7]  J. Vederas,et al.  Putative Diels-Alder-Catalyzed Cyclization during the Biosynthesis of Lovastatin. , 1996, The Journal of organic chemistry.

[8]  Stuart L Schreiber,et al.  A planning strategy for diversity-oriented synthesis. , 2004, Angewandte Chemie.

[9]  É. Marsault,et al.  The transannular Diels-Alder strategy: applications to total synthesis , 2001 .

[10]  Zhen Yang,et al.  Development of a concise and diversity-oriented approach for the synthesis of plecomacrolides via the diene-ene RCM. , 2006, Organic letters.

[11]  E. Corey,et al.  Useful enantioselective bicyclization reactions using an N-protonated chiral oxazaborolidine as catalyst. , 2003, Organic letters.

[12]  A. Bose,et al.  Preparation of both enantiomers of an α-hydroxy ketone via biocatalytic reduction and chemical oxidation , 1993 .

[13]  Andrew Kopecky,et al.  Pseudoephedrine as a Practical Chiral Auxiliary for the Synthesis of Highly Enantiomerically Enriched Carboxylic Acids, Alcohols, Aldehydes, and Ketones , 1997 .

[14]  J. Petersen,et al.  Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis , 1985 .

[15]  C. Debitus,et al.  Drimane Sesquiterpenes from the Sponge Dysidea fusca , 1996 .

[16]  G. Habermehl,et al.  ReviewPure appl. Chem: Rinehart, K. L., et al. Marine natural products as sources of antiviral, antimicrobial, and antineoplastic Agents. 53, 795 (1981). (K. L. Rinehart, University of Illinois, Urbana, IL 61801, U.S.A.) , 1983 .

[17]  P. Deslongchamps.  Transannular Diels-Alder reaction on macrocycles. A general strategy for the synthesis of polycyclic compounds , 1992 .