4. New Reagents for Asymmetric Aldol Reactions.

The development of general and experimentally straightforward procedures for the asymmetric synthesis of β-hydroxyketones by aldol reactions of ketones with aldehydes is of continuing interest. These aldol products are immensely valuable in the total synthesis of complex polyoxygenated compounds. We have introduced a range of chiral ketones, which undergo highly diastereoselective syn and anti aldol reactions with aldehydes using kinetically generated boron enolates. In certain cases, 1,4-, 1,5- and even 1,6-stereoinduction is possible, enabling the control of remote stereocentres in acyclic systems. Moreover, asymmetric ethyl and methyl ketone aldol additions can be performed using chiral boron reagents (Ipc2BX, X = Cl or OTf) prepared from (+)- or (-)-α-pinene. These reagents control the relative and absolute stereochemistry of C—C bond formation between achiral and chiral ketones and aldehydes, thus providing a powerful new synthetic method.

stereoinduction in aldol reactions

Selected publications:

  1. Cowden, C. J.; Paterson, I. Asymmetric aldol reactions using boron enolates. Org. React. 1997, 51, 1.
  2. Paterson, I.; Wallace, D. J.; Cowden, C. J. Polyketide synthesis using the boron-mediated, anti aldol reactions of lactate-derived ketones: total synthesis of (—)-ACRL Toxin IIIB. Synthesis 1998, 639.
  3. Paterson, I.; Gibson. K. R.; Oballa, R. M. Remote, 1,5-anti stereoinduction in the boron-mediated aldol reactions of β-oxygenated methyl ketones. Tetrahedron Lett. 1996, 37, 8585.
  4. Paterson, I.; Wallace, D. J.; Velazquez, S. M. Studies in polypropionate synthesis: high π-face selectivity in syn and anti aldol reactions of chiral boron enolates of lactate-derived ketones. Tetrahedron Lett. 1994, 35, 9083.
  5. Paterson, I.; Wallace, D. J. Manipulation of the aldol adducts from lactate-derived ketones. A versatile chiral auxiliary for the asymmetric synthesis of β-hydroxy carbonyl compounds. Tetrahedron Lett. 1994, 35, 9087.
  6. Paterson, I.; Tillyer, R. D. Studies in polypropionate synthesis: high π-face selectivity in syn aldol reactions of Sn(II) enolates from (R)- and (S)-1-(benzyloxy)-2-methylpentan-3-one. Tetrahedron Lett. 1992, 33, 4233.
  7. Paterson, I.; Goodman, J. M.; Lister, M. A.; Schumann, R. C.; McClure, C. K.; Norcross, R. D. Enantio- and diastereoselective aldol reactions of achiral ethyl and methyl ketones with aldehydes: the use of enol diisopinocampheyl-borinates. Tetrahedron 1990, 46, 4663.

Current Projects

  1. Synthesis of Bioactive Marine Metabolides.
  2. New Methods for the Synthesis of Polyketide Natural Products.
  3. Expanding Polyketide Diversity.
  4. New Reagents for Asymmetric Aldol Reactions.
  5. Biomimetic Total Synthesis of Polyether Ionophores.
  6. Designed Synthesis of Lophotoxin Analogues.
  7. Designed Synthesis of Novel Macrolide Antibiotics Related to Erythromycin.
  8. Transition State Modelling of Reactions (with Dr J. M. Goodman and Prof C. Gennari)