Asymmetric hetero-Diels-Alder (HDA) reactions of N-sulfinyl dienophiles using bis(oxazoline)-copper(II) and -zinc(II) triflates are described. The cycloadditions with cyclic and acyclic 1,3-dienes have been studied. In most cases, good enantioselectivities (70-98% ee) and yields (60-85%) were obtained with stoichiometric amounts of the Lewis acids. Cyclic dienes gave the endo adducts as major products, while acyclic dienes provided cis adducts. The HDA adducts have been transformed into N-protected alpha-amino acid methyl esters, amino alcohols, and homoallylic amines. A stereochemical model, which accounts for the enantiofacial selectivity of the HDA reaction by a tetrahedral metal center, has been proposed. Mechanistic studies revealed positive nonlinear effects, assumed to arise from the formation of less-reactive heterochiral complexes. Investigation of the temperature dependence of the enantioselectivity indicated that at least two selective reaction steps exist in the zinc-catalyzed reaction. Reactions run with 10 mol % chiral Lewis acid gave poor yields and selectivities. However, in combination with TMSOTf (100 mol %), high yields (68-86%) and enantioselectivities (97-98% ee) were obtained.

Asymmetric hetero Diels–Alder (HDA) reactions of N‐sulfinyldienophiles with bis(oxazoline)copper(II) and ‐zinc(II) triflatesare described. The cycloaddition with cyclic and acyclic 1,3‐dienes has been studied. The copper catalyst was found to be more efficient. With 10 mol‐% of catalyst loading, a pronounced enhancement in turnover, diastereoselectivity (54–>90 % de), and enantioselectivity (30–98 % ee) was obtained by the addition of 100 mol‐% of TMSOTf. The role of the additive is unclear, but we hypothesize that it is involved in the breakdown of catalyst‐sulfine aggregates assists in the release of catalyst from the HDA adducts. Mechanistic studies revealed a positive nonlinear effect with the zinc catalyst, assumed to arise from the formation of less reactive heterochiral complexes. The copper catalyst showed a nearly linear relationship between the enantioselectivity of the ligand tested and the HDA product formed. The relative configurations and, in one case, the absolute configuration of the HDA products were established by X‐ray analysis. Finally, an enantioselective route to (3aR,6aS)‐3,3a,4,6a‐tetrahydrocyclopenta[d][1,3]oxazol‐2‐one, a precursor of the C‐ring in agelastatin A, applying the asymmetric HDA reaction is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

S N R O + chiral Lewis acid CH 2 Cl 2 1c-i 3c-i 2 up to 97% ee S N R OA series of N-sulfinyl dienophiles 1c-i has been screened in asymmetric hetero-Diels-Alder reactions using chiral bis(oxazoline)copper(II) and -zinc(II) triflates. The survey pointed out N-sulfine 1c (R = P(=O)(OPh) 2 ) as the most promising N-sulfine regarding yield and stereoselectivity (up to 97% ee). The relative configurations, and in one case the absolute configuration, of the HDA adducts were established by X-ray analysis.selected to elucidate the scope and limitations of the asymmetric HDA reaction.

Chiral Bis(oxazoline)-Copper(II) and -Zinc(II) Triflates. -It is found that asymmetric hetero-Diels-Alder reactions of N-sulfinyl dienophiles can be performed effectively in the presence of stoichiometric and catalytic amounts of the complexes Cu(O-Tf)2/(Ia), Cu(O-Tf)2/(Ic), Zn(O-Tf)2/(Ia), and Zn(O-Tf)2/(Ic). The resulting products are useful synthons which can easily be transformed into various compounds. -(BAYER, A.; ENDESHAW, M. M.; GAUTUN*, O. R.; J. Org. Chem. 69 (2004) 21, 7198-7205; Dep. Chem., Norw. Univ. Sci. Technol., N-7491 Trondheim, Norway; Eng.) -Jannicke 07-157

Hetero-Diels-Alder Reactions. -Several N-sulfinyl dienophiles (I) are screened in Cu-or Zn-catalyzed asymmetric hetero-Diels-Alder reactions with cyclohexadiene in the presence of chiral bisoxazoline ligands. Derivative (Ia) appears to be a promising dienophile with respect to product yield and stereoselectivity (up to 97% e.e.). -(ENDESHAW, M. M.; HANSEN, L. K.; GAUTUN*, O. R.; J. Heterocycl. Chem. 45 (2008) 1, 149-154; Dep. Chem., Norw. Univ. Sci. Technol., N-7491 Trondheim, Norway; Eng.) -R. Staver 19-163