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. 2009 Feb 25;131(7):2514-20.
doi: 10.1021/ja808857w.

anti-Diastereo- and enantioselective carbonyl crotylation from the alcohol or aldehyde oxidation level employing a cyclometallated iridium catalyst: alpha-methyl allyl acetate as a surrogate to preformed crotylmetal reagents

In Su Kim  1 , Soo Bong Han, Michael J Krische
Affiliations

anti-Diastereo- and enantioselective carbonyl crotylation from the alcohol or aldehyde oxidation level employing a cyclometallated iridium catalyst: alpha-methyl allyl acetate as a surrogate to preformed crotylmetal reagents

In Su Kim et al. J Am Chem Soc. .

Abstract

Under the conditions of transfer hydrogenation employing an ortho-cyclometallated iridium catalyst generated in situ from [Ir(cod)Cl](2), 4-cyano-3-nitrobenzoic acid and the chiral phosphine ligand (S)-SEGPHOS, alpha-methyl allyl acetate couples to alcohols 1a-1j with complete levels of branched regioselectivity to furnish products of carbonyl crotylation 3a-3j, which are formed with good levels of anti-diastereoselectivity and exceptional levels of enantioselectivity. An identical set of optically enriched carbonyl crotylation products 3a-3j is accessible from the corresponding aldehydes 2a-2j under the same conditions, but employing isopropanol as the terminal reductant. Experiments aimed at probing the origins of stereoselection establish a matched mode of ionization for the (R)-acetate and the iridium catalyst modified by (S)-SEGPHOS, as well as reversible ionization of the allylic acetate with rapid pi-facial interconversion of the resulting pi-crotyl intermediate in advance of C-C bond formation. Additionally, rapid alcohol-aldehyde redox equilibration in advance of carbonyl addition is demonstrated. Thus, anti-diastereo- and enantioselective carbonyl crotylation from the alcohol or aldehyde oxidation level is achieved in the absence of any stoichiometric metallic reagents or stoichiometric metallic byproducts.

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Figures

Scheme 1
Scheme 1
Carbonyl crotylation from the alcohol or aldehyde oxidation level via transfer hydrogenative C-C coupling.
Scheme 2
Scheme 2
Experiments aimed at probing the origins of stereoselection in Ir-catalyzed transfer hydrogenative crotylation (Ar = (4-(CO2Me)Ph). aReactions were performed in 13 × 100 mm pressure tubes. Cited yields are of material isolated by silica gel chromatography. Enantiomeric excess was determined by chiral stationary phase HPLC analysis via comparison to racemic diastereomeric mixtures. See experimental section for further details.
Scheme 3
Scheme 3
Stereochemical features associated with formation and isomerization of the purported crotyl iridium intermediates (*Ln = (S)-SEGPHOS and C,O-benzoate of 4-cyano-3-nitrobenzoic acid I).
Scheme 4
Scheme 4
Experiments establishing rapid redox equilibration in advance of carbonyl addition (Ar = (4-(CO2Me)Ph).a aReactions were performed in 13 × 100 mm pressure tubes. Cited yields are of material isolated by silica gel chromatography. See experimental section for further details.
Scheme 5
Scheme 5
Left: Simplified catalytic mechanism proposed for the iridium catalyzed transfer hydrogenative crotylation. Right: Model accounting for the observed sense of relative and absolute stereocontrol.
See this image and copyright information in PMC

References

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