[RhOH((S)-BINAP)]2 (1), [RhOMe((S)-BINAP)]2 (2), and Catalyst Precursors

ChemFiles Volume 5 Article 10

In the late 1990s, the Hayashi group successively developed rhodium-based catalysts applied in the asymmetric, conjugate addition of arylboronic acids to C=C bonds.1 They utilized Rh-BINAP catalysts to effect several advantages over other enantioselective 1,4-addition reactions: 1) high selectivities (>95% ee) have been attained; 2) the reaction is performed in an aqueous environment; 3) the reaction temperature is not low (60–90 °C) and thus is advantageous for process design; 4) a multitude of aryl and alkenyl groups can be incorporated; and 5) a variety of electron-deficient olefins can be effectively coupled with boronic acids in an asymmetric fashion.

We are now pleased to offer the latest technology from Hayashi, including both the pre-catalysts suitable for facile conversion into the active species, as well as the catalysts themselves (Scheme 3). Rh-dimer catalysts 1 and 2 offer additional benefits over their monomeric counterparts: 1) the reaction is carried out at ambient temperatures, which limits the amount of boron reagent needed by eliminating decomposition at higher temperatures; 2) the yield of 1,4-addition product is typically higher due to a reduction of arylboronic acid hydrolysis; and 3) the enantioselectivities are always higher in reactions catalyzed by [RhOH((S)-BINAP)]2 and [RhOMe((S)-BINAP)]2 than by Rh(acac)(BINAP).2 In general, the Hayashi system displays impressive levels of enantiocontrol in the reactions of both acyclic and cyclic enones of varying electronic character, affording highly enantioenriched products in excellent yields (Scheme 4, Table 1).

Scheme 3

Scheme 4

Table 1

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Cobalt Oxazoline Palladacycles: COP-Cl (5) and COP-OAc (6)

Overman and co-workers have successfully synthesized dimeric cobalt catalysts that effectively promote the asymmetric rearrange-ment of allylic trichloroacetimidates to allylic trichloroacetamides.3 The rationale for this transformation is obvious as it grants ready access to valuable allylic amines of high enantiopurity, following the removal of the trichloroacetyl group under acidic, basic, or reductive conditions (Scheme 5). The high levels of asymmetry induced by COP catalysts in the preparation of chiral allylic amines can be carried forth into low-molecular weight compounds such as (S)-Vigabatrin, a GABA aminotransaminase inhibitor.4 Sigma-Aldrich has already introduced COP-Cl 5, and now has commercialized the acetate-bridged COP dimer 6, which has enhanced performance characteristics versus COP-Cl due to its increased solubility in non-chlorinated solvents (Scheme 6).

Scheme 5

Scheme 6

COP-OAc also catalyzes the asymmetric rearrangement of prochiral (Z)-allylic trichloroacetimidates in the presence of carboxylic acids to the corresponding chiral allylic esters with high enantiopurities (Scheme 7).5 The scope of the reaction when utilizing an n-propyl-substituted allylic imidate at ambient temperature includes a wide range of aliphatic and aromatic carboxylic acids with high enantioselectivities of 3-acyloxy-1-alkene products (93–99%, Table 2). Good yields (60–98%) of the chiral allylic alcohols and heteroatom substituent tolerance on the allylic imidate ensure that this methodology will be attractive for broader application on the pathway to natural product synthesis.

Scheme 7

Table 2

Another promising feature of this catalyst system is found in the recent literature, wherein COP-OAc dimer 6 promotes the intramolecular aminopalladation of allylic N-tosylcarbamates to afford highly enantioenriched 2-vinyloxazolidin-2-ones.6 The COP-OAc catalyst exhibits superior activity and avoids the use of silver salts for pre-activation, thereby leveraging a distinct advantage over the earlier catalyst models studied by Overman. Furthermore, crude allylic N-tosylcarbamate reagents can be prepared in situ following the addition of an allylic alcohol to an N-sulfonylisocyanate and subsequently cyclized with excellent selectivity (Scheme 8).

Scheme 8

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  1. (a) Hayashi, T. et al. J. Am. Chem. Soc. 2002, 124, 5052. (b) Hayashi, T. et al. Chem. Rev. 2003, 103, 2829.
  2. (a) Hayashi, T. et al. J. Am. Chem. Soc. 1998, 120, 5579. (b) Hayashi, T. et al. Tetrahedron: Asymmetry 1999, 10, 4047. (c) Hayashi, T. et al. Tetrahedron Lett. 1999, 40, 6957.
  3. (a) Overman, L. E. et al. J. Org. Chem. 2004, 69, 8101. (b) Overman, L. E. et al. J. Am. Chem. Soc. 2003, 125, 12412.
  4. Smith, M. B. J. Org. Chem. 1992, 57, 6169 and ref. 20 therein.
  5. Overman, L. E. et al. J. Am. Chem. 2005, 127, 2866.
  6. Overman, L. E. et al. J. Org. Chem. 2005, 70, 2859.

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