Mislow-Evans Rearrangement

Dan Tao

Overman Group Meeting

9/24/12

Quick Sulfur Nomenclature

Thiol

Sulfoxide

Sulfone

Sulfonate Ester

Sulfate

Sulfenate Ester

Sulfinate Ester

What is the Mislow-Evans

Rearrangement? • It is a [2,3]-sigmatropic rearrangement of an allylic sulfoxide to a sulfenate ester, which can then be cleaved to the allylic alcohol

• As with all sigmatropic rearrangements, it is in equilibrium. Addition of a thiophile funnels the equilibrium to the allylic alkoxide.

Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc. 1968, 90, 4869. Prilezhaeva, E. N. Russian Chemical Reviews 2001, 70, 897.

• The thiophiles can be phosphorus-, sulfur-, or nitrogen-based nucleophiles

Initial Discovery by Mislow

• In 1968, Mislow noticed that an enantiopure allylsulfoxide was

racemizing at elevated temperatures

• Mislow states “The transition state for the rearrangement… corresponds

to a concerted, cyclic process… ”

Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc. 1968, 90, 4869.

Evan’s Application • In 1971, D. Evans applied this rearrangement in a useful method to make

functionalized allylic alcohols

Evans, D. A.; Andrews, G. C.; Sims, C. L. J. Am. Chem. Soc. 1971, 93, 4956. Evans, D. A.; Andrews, G. C. Acc. Chem. Res. 1974, 7, 147.

• Choice of thiophile can affect the stereochemical outcome

Stereochemical Significance

• Stereochemical information is completely transferred from the sulfoxide to the sulfenate

• As the sulfoxide and sulfenate ester are in equilibrium, enantiopurity will degrade the with heat or over time

Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc. 1968, 90, 4869.

Transition State • The Mislow-Evans transition state is highly ordered, preferring to form the E olefin (unless within a small ring)

•In the case of chirality on the sulfur, stereochemistry is transferred from S to C while maintaining the E olefin (or Z in small rings)

Hoffmann, R. W. Angew. Chem., Int. Ed. 1979, 18, 563. Evans, D. A.; Andrews, G. C.; Sims, C. L. J. Am. Chem. Soc. 1971, 93, 4956.

Early Use in Prostaglandin Synthesis

Miller, J. G. Kurz, W.; Untch, K. G.; Stork, G. J. Am. Chem. Soc. 1974, 96, 6774.

• The cis-cuprate gave much higher yields and stereospecificity • A trans olefin is required for the prostaglandins

Early Use in Prostaglandin Synthesis

Taber, D. F. J. Am. Chem. Soc. 1977, 99, 3513.

Multiple Rearrangements in Synthesis • Cascade Claisen/Mislow-Evans Rearrangements

Pelc, M. J.; Zakarian, A. Tetrahedron Lett. 2006, 47, 7519.

Multiple Rearrangements in Synthesis • Overman/Mislow-Evans Rearrangements

Hama, N.; Matsuda, T.; Sato, T.; Chida, N. Org. Lett. 2009, 11, 2687.

Tandem Diels-Alder and Mislow-Evans

Pelc, M. J.; Zakarian, A. Tetrahedron Lett. 2006, 47, 7519. Evans, D. A.; Bryan, C. A.; Sims, C. L. J. Am. Chem. Soc. 1972, 94, 2891.

Acid-Catalyzed Mislow-Evans

• Though limited in substrate scope, an alternative to thiophiles is using

acid in a one-pot procedure

Masaki, Y.; Sakuma, K.; Kaji, K. Chem. Pharm. Bull. 1985, 33, 2531.

Inversion (Alternative to Mitsunobu)

Majetich, G.; Song, J. S.; Ringold, C.; Nemeth, G. A.; Newton, M. G. J. Org. Chem. 1991, 56, 3973. Paquette, L. A.; Meister, P. G.; Friedrich, D.; Sauer, D. R. J. Am. Chem. Soc. 1993, 115, 49.

Seleno-Mislow-Evans Rearrangement • Irreversible when in the presence of excess oxidant (Forms R-SeO2H)

Zanoni, G.; Porta, A.; Castronovo, F.; Vidari, G. J. Org. Chem. 2003, 68, 6005. Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44, 3485.

Summary

• The Mislow-Evans rearrangement is a [2,3]-sigmatropic rearrangement of an allylic sulfoxide to a sulfenate ester which can be irreversibly cleaved to an allylic alcohol

Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc. 1968, 90, 4869. Prilezhaeva, E. N. Russian Chemical Reviews 2001, 70, 897.

• Its highly-ordered cyclic transition state completely transfers chirality from either carbon or sulfur to a product with a E olefin (Z in small rings)

• This rearrangement is often applied in complex molecules using mild conditions with high yields