Novel chemistry of alpha-tosyloxy ketones: applications to the solution- and solid-phase synthesis of privileged heterocycle and enediyne libraries

TY - JOUR

T1 - Novel chemistry of alpha-tosyloxy ketones: applications to the solution- and solid-phase synthesis of privileged heterocycle and enediyne libraries

AU - Nicolaou, K C

AU - Montagnon, T

AU - Ulven, T

AU - Baran, P S

AU - Zhong, Y-L

AU - Sarabia, F

PY - 2002/5/22

Y1 - 2002/5/22

N2 - New synthetic technologies for the preparation and elaboration of alpha-tosyloxy ketones in solution- and on solid-phase are described. Both olefins and ketones serve as precursors to these relatively stable chemical entities: olefins via a novel one-pot epoxidation, arylsulfonic acid displacement, and oxidation sequence, and ketones by direct exposure to arylsulfonic acids in the presence of diacetoxy iodobenzene. Reaction of these substrates with O-, S-, or N-centered nucleophiles leads to incorporation of the nucleophile with concomitant expulsion of the sulfonate, while exposure to bis-functional nucleophiles furnishes annulated heterocyclic systems. In addition, the reactions of carbon-centered nucleophiles with alpha-tosylyloxy ketones are also explored. The collated data for all these nucleophiles provide compelling evidence for the proposal that different reaction pathways are followed when alpha-tosyloxy ketones are engaged by "hard" versus "soft" nucleophiles. The accessibility and site-selectivity of the chemistry demonstrated herein offer the promise of an expanded use for this moiety in solid-phase library construction, in particular, and in the field of organic synthesis, in general.

AB - New synthetic technologies for the preparation and elaboration of alpha-tosyloxy ketones in solution- and on solid-phase are described. Both olefins and ketones serve as precursors to these relatively stable chemical entities: olefins via a novel one-pot epoxidation, arylsulfonic acid displacement, and oxidation sequence, and ketones by direct exposure to arylsulfonic acids in the presence of diacetoxy iodobenzene. Reaction of these substrates with O-, S-, or N-centered nucleophiles leads to incorporation of the nucleophile with concomitant expulsion of the sulfonate, while exposure to bis-functional nucleophiles furnishes annulated heterocyclic systems. In addition, the reactions of carbon-centered nucleophiles with alpha-tosylyloxy ketones are also explored. The collated data for all these nucleophiles provide compelling evidence for the proposal that different reaction pathways are followed when alpha-tosyloxy ketones are engaged by "hard" versus "soft" nucleophiles. The accessibility and site-selectivity of the chemistry demonstrated herein offer the promise of an expanded use for this moiety in solid-phase library construction, in particular, and in the field of organic synthesis, in general.

KW - Alkynes

KW - Heterocyclic Compounds

KW - Ketones

KW - Tosyl Compounds

M3 - Journal article

SN - 0002-7863

VL - 124

SP - 5718

EP - 5728

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 20

ER -