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Queen's University

Chemistry Department

90 Bader Lane

Kingston, Ontario

K7L 3N6

 

 

 

 

 

Research

 

 

Rhodium-Catalyzed Higher Order Carbocyclization Reactions

The Evans group has reported a number of rhodium-catalyzed higher order [(m+n)+o] carbocyclization reactions for the construction of polycyclic systems. We recently isolated and characterized the rhodacycle implicated in the stereoselective carbocyclization and ene-cycloisomerization reactions of alkylidenecyclopropanes (ACPs), which has provided key insight into the ligand requirements for the insertion and reductive elimination of various p-components.  Furthermore, we have demonstrated that not only are these species catalytically competent, but that they can also be employed as formal [(3+2)] synthons in the discovery of new carbocyclization reactions, exemplified by the [(3+2)+2] reaction of ACPs with allenes.

P. A. Evans and P. A. Inglesby. J. Am. Chem. Soc. 2008, 130, 12838.

P. A. Evans and P. A. Inglesby. J. Am. Chem. Soc. 2012, 134, 3635.

S. Mazumder, D. Shang, D. E. Negru, Mu-Hyun Baik and P. A. Evans. J. Am. Chem. Soc. 2012, 134, 20569.

P. A. Evans, D. E. Negru and D. Shang. Angew. Chem. Int. Ed. 2015, 54, 4768.

(Rhodacycle Isolation/Characterization)

P. A. Inglesby, J. Bacsa, D. E. Negru and P. A. Evans. Angew. Chem. Int. Ed. 2014, 53, 3952.

(Review)

P. A. Inglesby and P. A. Evans. Chem. Soc. Rev. 2010, 39, 2791.

 

Rhodium-Catalyzed Allylic Substitution Reactions

The Evans group has developed a highly regio- and enantiospecific rhodium-catalyzed allylic substitution reaction of secondary and tertiary carbonates with a number of carbon and heteroatom-based nucleophiles (Path A).  Recently, we have shown that the use of a chiral monodentate phosphite ligand enables the highly enantioselective allylic alkylation of prochiral nucleophiles with unsubstituted allyl electrophiles (Path B).

(Path A)

P. A.Evans and J. D. Nelson. J. Am. Chem. Soc. 1998, 120, 5581.

P. A. Evans, S.Oliver and J. Chae. J. Am. Chem. Soc. 2012, 134, 19314.

B. W. H. Turnbull, S. Oliver and P. A. Evans. J. Am. Chem. Soc. 2015, 137, 15374.

(Path B)

P. A. Evans, E. A. Clizbe, M. J. Lawler and S. Oliver. Chem. Sci. 2012, 3, 1835.

B. W. H. Turnbull and P. A. Evans. J. Am. Chem. Soc. 2015, 137, 6156.

(Reviews)

D. K. Leahy and P. A. Evans in Modern Rhodium-Catalyzed Organic Reactions; P. A. Evans, Ed.; Wiley-VCH: Weinheim, Germany, 2005; Ch. 10, p. 191-214.

S. Oliver and P. A. Evans. Synthesis 2013, 45, 3179.

 

Transition Metal-Catalyzed Allylic Amination with Aza-Ylides

The Evans group were the first to describe the use of charge-separated pronucleophiles in the transition metal-catalyzed allylic amination reaction.  The aza-ylide derived from 1-aminopyridinium iodide provides a convenient ammonia equivalent in the regio- and enantiospecific rhodium-catalyzed allylic amination.  Additionally, the highly regio- and enantioselective iridium-catalyzed allylic amination with the sulfur-stabilized aza-ylide S,S-diphenylsulfilimine offers a novel route to C-chiral allylic sulfilimines, which can partake in a novel methathesis reaction with aryl isocyanates for the construction of unsymmetrical ureas, carbamates, thiocarbamates and amides.

P. A. Evans and E. A. Clizbe. J. Am. Chem. Soc. 2009, 131, 8722.

R. L. Grange and P. A. Evans. J. Am. Chem. Soc. 2014, 136, 11870.

R. L. Grange, E. A. Clizbe, E. J. Counsell and P. A. Evans. Chem. Sci. 2015, 6, 777.

 

Bismuth-Mediated Hetero-Conjugation Reactions

The Evans group has demonstrated that bismuth(III) salts facilitate a number of acid-catalyzed  reactions with unique reactivity and selectivity as a result of their ability to modulate the acid concentration and thereby buffer the reaction.  We have recently developed the bismuth-mediated two-component hemiacetal/oxa-conjugate addition reaction for the highly diastereoselective construction of syn-1,3-dioxanes and anti-1,3-dioxolanes, which provide convenient precursors to syn-1,3- and 1,2-diols, respectively.

P. A. Evans, A. Grisin and M. J. Lawler. J. Am. Chem. Soc. 2012, 134, 2856.

A. Grisin, S. Oliver, M. D. Ganton, J. Bacsa and P. A. Evans. Chem. Commun. 2015, 51, 15681.

 

Temporary Silicon-Tethered Ring-Closing Metathesis (TST-RCM) Reactions

The Evans group has pioneered the use of TST-RCM for the stereoselective construction of a diverse range of polyol and polypropionate fragments.  The temporary silicon-tethered ring-closing metathesis of enantiomerically enriched allylic and homoallylic alcohols furnishes geometrically pure Z-trisubstituted olefins, which can undergo stereoselective hydroboration and dihydroxylation to provide motifs present in important bioactive polyketides.

P. A. Evans, J. Cui and G. P. Buffone. Angew. Chem. Int. Ed. 2003, 42, 1734.

P. A. Evans, A. Cusak, A. Grisin and M. J. Lawler. Synthesis 2016, Accepted.

 

Total Synthesis of Natural Products (Current and Past Targets)

The Evans group is actively engaged in utilizing the methodology we develop toward the total synthesis of complex, bioactive natural products.  For example, rhodium-catalyzed carbocyclization and ene-cycloisomerizations have been used towards the total synthesis of the sesquiterpene natural products pyrovellerolactone and repin and the non-proteinogenic amino acid (−)-α-kainic acid, respectively.  Additionally, rhodium-catalyzed allylic amination was used in the concise synthesis of the alkaloid (−)-batzelladine D.  Total syntheses of the macrolides (+)-leucascandrolide A and marinomycin A feature the bismuth-mediated heteroconjugation reactions.  Finally, the the temporary silicon-tethered ring-closing metathesis (TST-RCM) was successfully employed in the construction of the polyketide natural products (−)-mucocin and the C1-C31 Fragment of Amphidinol 3.

 


 Last updated: 20 May 2017
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