We
report the development of a Pd-catalyzed process for the stereospecific
cross-coupling of unactivated secondary alkylboron nucleophiles and
aryl chlorides. This process tolerates the use of secondary alkylboronic
acids and secondary alkyltrifluoroborates and occurs without significant
isomerization of the alkyl nucelophile. Optically active secondary
alkyltrifluoroborate reagents undergo cross-coupling reactions with
stereospecific inversion of configuration using this method.
A mild Pd-catalyzed process for the borylation of alkyl bromides has been developed using bis(pinacolato)diboron as a boron source. This process accommodates the use of a wide range of functional groups on the alkyl bromide substrate. Primary bromides react with complete selectivity in the presence of a secondary bromide. The generality of this approach is demonstrated by its extension to the use of alkyl iodides and alkyl tosylates, as well as borylation reactions employing bis(neopentyl glycolato)diboron as the boron source.
A novel strategy employing cyclohexyl spectator ligands in Stille cross-coupling reactions has been developed as a general solution to the long-standing challenge of conducting stereospecific cross-coupling reactions at nitrogen-containing stereocenters. This method enables direct access to enantioenriched products that are difficult (or impossible) to obtain via alternative preparative methods. Selective and predictable transfer of a single secondary alkyl unit can be achieved under reaction conditions that exploit subtle electronic differences between activated and unactivated alkyl units. Through this approach, enantioenriched α-stannylated nitrogen-containing stereocenters undergo Pd-catalyzed arylation and acylation reactions with exceptionally high stereofidelity in all instances investigated. We demonstrate this process by using α-stannylated pyrrolidine, azetidine, and open-chain (benzylic and non-benzylic) nucleophiles in stereospecific reactions. This process will facilitate rapid and reliable access to enantioenriched compounds possessing nitrogen-substituted stereocenters, which constitute ubiquitous structural motifs in biologically active compounds emerging from the drug-discovery process.
We report the use of isolable primary and secondary alkylcarbastannatrane nucleophiles in site‐specific fluorination reactions. These reactions occur without the need for transition metal catalysis or in situ activation of the nucleophile. In the absence of the carbastannatrane backbone, alkyltin nucleophiles exhibit no activity towards fluorination. When enantioenriched alkylcarbastannatranes are employed, fluorination occurs predominately via a stereoinvertive mechanism to generate highly enantioenriched alkyl fluoride compounds. These conditions can also be extended to stereospecific chlorination, bromination, and iodination reactions.
We report the use of isolable primary and secondary alkylcarbastannatrane nucleophiles in site-specific fluorination reactions. These reactions occur without the need for transition metal catalysis or in situ activation of the nucleophile. In the absence of the carbastannatrane backbone, alkyltin nucleophiles exhibit no activity towards fluorination. When enantioenriched alkylcarbastannatranes are employed, fluorination occurs predominately via a stereoinvertive mechanism to generate highly enantioenriched alkyl fluoride compounds. These conditions can also be extended to stereospecific chlorination, bromination, and iodination reactions.
Chlorides. -The Pd-catalyzed cross-coupling of aryl chlorides with secondary alkylboronic acids and secondary alkyl trifluoroborates is developed. Optically active alkyl trifluoroborates react with inversion of configuration. -(LI, L.; ZHAO, S.; JOSHI-PANGU, A.; DIANE, M.; BISCOE*, M. R.; J. Am. Chem. Soc. 136 (2014) 40, 14027-14030, http://dx.doi.org/10.1021/ja508815w ; Dep. Chem., City Coll., City Univ., New York, NY 10031, USA; Eng.) -Mais 16-065
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