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. 2008 Nov 5;130(44):14891-9.
doi: 10.1021/ja805722e. Epub 2008 Oct 8.

Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level via transfer hydrogenative coupling of allyl acetate: departure from chirally modified allyl metal reagents in carbonyl addition

In Su Kim  1 , Ming-Yu Ngai, Michael J Krische
Affiliations

Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level via transfer hydrogenative coupling of allyl acetate: departure from chirally modified allyl metal reagents in carbonyl addition

In Su Kim et al. J Am Chem Soc. .

Abstract

Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ from [Ir(cod)Cl]2, chiral phosphine ligand (R)-BINAP or (R)-Cl,MeO-BIPHEP, and m-nitrobenzoic acid, allyl acetate couples to allylic alcohols 1a-c, aliphatic alcohols 1d-l, and benzylic alcohols 1m-u to furnish products of carbonyl allylation 3a-u with exceptional levels of asymmetric induction. The very same set of optically enriched carbonyl allylation products 3a-u are accessible from enals 2a-c, aliphatic aldehydes 2d-l, and aryl aldehydes 2m-u, using iridium catalysts ligated by (-)-TMBTP or (R)-Cl,MeO-BIPHEP under identical conditions, but employing isopropanol as a hydrogen donor. A catalytically active cyclometallated complex V, which arises upon ortho-C-H insertion of iridium onto m-nitrobenzoic acid, was characterized by single-crystal X-ray diffraction. The results of isotopic labeling are consistent with intervention of symmetric iridium pi-allyl intermediates or rapid interconversion of sigma-allyl haptomers through the agency of a symmetric pi-allyl. Competition experiments demonstrate rapid and reversible hydrogenation-dehydrogenation of the carbonyl partner in advance of C-C coupling. However, the coupling products, which are homoallylic alcohols, experience very little erosion of optical purity by way of redox equilibration under the coupling conditions, although isopropanol, a secondary alcohol, may serve as terminal reductant. A plausible catalytic mechanism accounting for these observations is proposed, along with a stereochemical model that accounts for the observed sense of absolute stereoinduction. This protocol for asymmetric carbonyl allylation transcends the barriers imposed by oxidation level and the use of preformed allyl metal reagents.

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Figures

Figure 1
Figure 1
Top: Representative examples of chirally modified allyl-metal reagents for use in enantioselective carbonyl allylation. Bottom: Prototypical catalytic enantioselective carbonyl allylations.
Figure 2
Figure 2
Structure assigned to a catalytically active ortho-cyclometallate diridium(III)-π-allyl complex V, as determined by single crystal X-ray diffraction analysis.a aThe figure graphics are depictions of crystallographic data imported into ChemBioDraw Ultra 11.0. For clarity, the binaphthyl moiety of the left structure was omitted.
Scheme 1
Scheme 1
Experiments corroborating intervention of ortho-cyclometallated iridium(III)-π-allyl complex V as a catalytically relevant entity.a aAll reactions were performed in 13 × 100 mm pressure tubes. The yields cited are of material isolated by silica gel chromatography. Enantiomeric excess was determined by chiral stationary phase HPLC analysis. See experimental section for further details.
Scheme 2
Scheme 2
Ir-catalyzed transfer hydrogenative allylation of benzylic alcohol 1n employing isotopically labeled allyl acetate.a aThe reaction was performed in a 13 × 100 mm pressure tube. The cited yield is of material isolated by silica gel chromatography. See experimental section for further details.
Scheme 3
Scheme 3
Experiments establishing rapid redox equilibration in advance of carbonyl addition.a aAll reactions were performed in 13 × 100 mm pressure tubes. The cited yields are of material isolated by silica gel chromatography. See experimental section for further details.
Scheme 4
Scheme 4
Postulated catalytic mechanisms for the iridium catalyzed transfer hydrogenative coupling from the alcohol or aldehyde oxidation level (Ln = chelating triaryl phosphine, e.g. (R)-BINAP or (R)-Cl,MeO-BIPHEP).
Figure 3
Figure 3
Proposed stereochemical model accounting for the observed sense of absolute stereoinduction based on single crystal X-ray diffraction data corresponding to complex V.a aThe figure graphics are modifications based on single crystal X-ray diffraction data corresponding to complex V, which were imported into ChemBioDraw Ultra 11.0. For clarity, the binaphthyl moiety has been truncated.
See this image and copyright information in PMC

References

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    1. A notable exception involves the chirally modified allyl silanes developed by Leighton (reference 3l), for which highly efficient recovery of the chiral auxiliary is possible.

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