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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 B 2 (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.

A highly chemo-, diastereo- and enantioselective catalytic method that efficiently combines a silyl hydride, vinyl-B(pin) (pin=pinacolato) and (E)-1,2-disubstituted allylic phosphates is introduced. Reactions, best promoted by a Cu-based complex with a chiral sulfonate-containing N-heterocyclic carbene, are broadly applicable. Aryl-, heteroaryl-, alkenyl-, alkynyl- and alkyl-substituted allylic phosphates may thus be converted to the corresponding homoallylic boronates and then alcohols (after C-B bond oxidation) in 46-91 % yield and in up to >98 % S N 2':S N 2 ratio, 96:4 diastereomeric ratio and 98:2 enantiomeric ratio. The reasons why an NHC-Cu catalyst is uniquely effective (vs. the corresponding phosphine systems) and the basis for different trends in stereoselectivity are provided with the aid of DFT calculations., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multicomponent catalytic enantioselective transformations that entail the combination of butadiene or isoprene (common feedstock), an enoate (prepared in one step) and B2 (pin)2 (commercially available) are presented. These processes constitute an uncommon instance of conjugate addition of an allyl moiety and afford the desired products in up to 83 % yield and 98:2 enantiomeric ratio. Based on DFT calculations stereochemical models and rationale for the observed profiles in selectivity are provided., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.

A highly chemo-, diastereo- and enantioselective catalytic method that efficiently combines a silyl hydride, vinyl-B(pin) (pin=pinacolato) and (E)-1,2-disubstituted allylic phosphates is introduced. Reactions, best promoted by a Cu-based complex with a chiral sulfonate-containing N-heterocyclic carbene, are broadly applicable. Aryl-, heteroaryl-, alkenyl-, alkynyl- and alkyl-substituted allylic phosphates may thus be converted to the corresponding homoallylic boronates and then alcohols (after C−B bond oxidation) in 46-91 % yield and in up to >98 % SN2′:SN2 ratio, 96:4 diastereomeric ratio and 98:2 enantiomeric ratio. The reasons why an NHC−Cu catalyst is uniquely effective (vs. the corresponding phosphine systems) and the basis for different trends in stereoselectivity are provided with the aid of DFT calculations. [ABSTRACT FROM AUTHOR]

A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well. [ABSTRACT FROM AUTHOR]

The first examples of allylic substitution reaction of allyl diethylphosphates with propargylated (pinacolato)boron compounds (II) are reported to provide generally branched products. [ABSTRACT FROM AUTHOR]