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. 2009;48(24):4349-53.
doi: 10.1002/anie.200900220.

Cycle-specific organocascade catalysis: application to olefin hydroamination, hydro-oxidation, and amino-oxidation, and to natural product synthesis

Bryon Simmons  1 , Abbas M Walji, David W C MacMillan
Affiliations

Cycle-specific organocascade catalysis: application to olefin hydroamination, hydro-oxidation, and amino-oxidation, and to natural product synthesis

Bryon Simmons et al. Angew Chem Int Ed Engl. 2009.

Abstract

United in effort: The combined application of iminium (Im) and enamine (En) catalysts can effect a range of valuable asymmetric transformations including 1,2-hydroamination, -hydro-oxidation, and -amino-oxidation of olefins (see picture). An enantioselective organocascade catalysis was also applied in the synthesis of a complex natural product.

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Figures

Scheme 1
Scheme 1
a) Absolute and relative stereocontrol in cycle-specific cascade catalysis. b) Imidazolidinone 1 and proline (2) as catalysts. LUMO=lowest unoccupied molecular orbital, HOMO=highest occupied molecular orbital.
Scheme 2
Scheme 2
Cycle-specific organocatalysis: representative electrophiles. Cbz=benzyloxycarbonyl, PMP=p-methoxyphenyl.
Scheme 3
Scheme 3
Cycle-specific organocatalysis: representative nucleophiles. TIPS=triisopropylsilyl, TBS=tert-butyldimethylsilyl, Boc=tert-butoxycarbonyl.
Scheme 4
Scheme 4
Proposed mechanism of the triple-cascade catalysis to generate the stereochemical core of aromadendranediol. 2,4-DNBA=2,4-dinitrobenzoic acid.
Scheme 5
Scheme 5
Total synthesis of (−)-aromadendranediol: a) Pd/C, 1 atm H2, EtOH, 23°C; LiAlH4, THF, 0°C, 85%; b) TESOTf, pyridine, CH2Cl2, 0°C, 95%; c) and d) DMSO, (CO)2Cl2, Et3N, −78 to −40°C, then MePPh3Br, nBuLi, THF, 0°C to RT, 72% (over two steps); e) Grubbs II, CH2ClCH2Cl, 70°C, 78%; f) KOtBu, CHBr3, hexane, 0°C, 96% single diastereomer; g) Me2CuLi, MeI, Et2O, −20 to 0°C, 99%; h) HF, MeCN, RT, 93%. TES=triethylsilyl.
See this image and copyright information in PMC

References

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    1. “Organocascade catalysis” describes the merger of two discrete organocatalytic cycles, each of which is involved the generation of stereogenic centers. For a comprehensive description see reference [1b].

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