Abstract
There are many biologically active organic molecules that contain one or more nitrogen-containing moieties, and broadly applicable and efficient catalytic transformations that deliver them diastereoselectively and/or enantioselectively are much sought after. Various methods for enantioselective synthesis of α-secondary amines are available (for example, from additions to protected/activated aldimines), but those involving ketimines are much less common. There are no reported additions of carbon-based nucleophiles to unprotected/unactivated (or N-H) ketimines. Here, we report a catalytic, diastereo- and enantioselective three-component strategy for merging an N-H ketimine, a monosubstituted allene and B2(pin)2, affording products in up to 95% yield, >98% diastereoselectivity and >99:1 enantiomeric ratio. The utility of the approach is highlighted by synthesis of the tricyclic core of a class of compounds that have been shown to possess anti-Alzheimer activity. Stereochemical models developed with the aid of density functional theory calculations, which account for the observed trends and levels of enantioselectivity, are presented.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Allyl Compounds / chemistry*
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Amines / chemical synthesis*
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Amines / chemistry
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Catalysis
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Copper / chemistry*
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Imines / chemistry*
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Molecular Structure
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Nitriles / chemistry*
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Organometallic Compounds / chemistry*
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Stereoisomerism
Substances
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Allyl Compounds
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Amines
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Imines
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Nitriles
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Organometallic Compounds
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ketimine
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Copper
Associated data
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PubChem-Substance/340079104
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PubChem-Substance/340079105
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PubChem-Substance/340079106
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PubChem-Substance/340079107
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PubChem-Substance/340079108
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PubChem-Substance/340079109
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PubChem-Substance/340079110
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PubChem-Substance/340079111
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PubChem-Substance/340079112
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PubChem-Substance/340079113
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PubChem-Substance/340079114
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PubChem-Substance/340079115
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PubChem-Substance/340079116
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PubChem-Substance/340079117
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PubChem-Substance/340079118
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PubChem-Substance/340079119
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PubChem-Substance/340079120
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PubChem-Substance/340079121
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PubChem-Substance/340079122
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PubChem-Substance/340079123
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PubChem-Substance/340079124
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PubChem-Substance/340079125
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PubChem-Substance/340079126
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PubChem-Substance/340079127
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PubChem-Substance/340079128
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PubChem-Substance/340079129
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PubChem-Substance/340079130
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PubChem-Substance/340079131
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PubChem-Substance/340079132
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PubChem-Substance/340079133
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PubChem-Substance/340079134
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PubChem-Substance/340079135
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PubChem-Substance/340079098
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PubChem-Substance/340079099
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PubChem-Substance/340079100
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PubChem-Substance/340079101
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PubChem-Substance/340079102
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PubChem-Substance/340079103