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.
P. A. Evans and P. A.
Inglesby. J. Am. Chem.
S. Mazumder, D. Shang, D. E.
Negru, Mu-Hyun Baik and P. A. Evans.
J. Am. Chem. Soc.
P. A. Evans, D. E. Negru and
D. Shang. Angew. Chem.
Int. Ed. 2015,
P. A. Inglesby, J. Bacsa, D.
E. Negru and P. A. Evans.
Angew. Chem. Int. Ed.
Inglesby and P. A. Evans.
Chem. Soc. Rev. 2010,
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).
P. A.Evans and J. D.
Nelson. J. Am. Chem. Soc.
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,
P. A. Evans, E. A.
Clizbe, M. J. Lawler and S. Oliver.
Chem. Sci. 2012,
B. W. H. Turnbull and P.
A. Evans. J. Am. Chem.
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.
S. Oliver and P. A.
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
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.
R. L. Grange and P. A.
Evans. J. Am. Chem. Soc.
R. L. Grange, E. A.
Clizbe, E. J. Counsell and P. A. Evans.
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
which provide convenient precursors to
P. A. Evans, A. Grisin
and M. J. Lawler. J. Am.
Chem. Soc. 2012,
A. Grisin, S. Oliver, M.
D. Ganton, J. Bacsa and P. A. Evans.
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
P. A. Evans, J. Cui and
G. P. Buffone. Angew.
Chem. Int. Ed. 2003,
P. A. Evans, A. Cusak, A. Grisin and
M. J. Lawler. Synthesis
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
acid, respectively. Additionally,
rhodium-catalyzed allylic amination was used in the concise
synthesis of the alkaloid
D. Total syntheses of
the macrolides (+)-leucascandrolide
A and marinomycin A feature the bismuth-mediated
Finally, the the temporary silicon-tethered ring-closing
metathesis (TST-RCM) was successfully employed in the
construction of the polyketide natural products
and the C1-C31 Fragment of Amphidinol 3.