Asymmetric Copper Hydride-Catalyzed Markovnikov Hydrosilylation of Vinylarenes and Vinyl Heterocycles

Abstract

We report a highly enantioselective CuH-catalyzed Markovnikov hydrosilylation of vinylarenes and vinyl heterocycles. This method has a broad scope and enables both the synthesis of isolable silanes and the conversion of crude products to chiral alcohols. Density functional theory calculations support a mechanism proceeding by hydrocupration followed by σ-bond metathesis with a hydrosilane.

Mechanism-based enhancement of scope and enantioselectivity for reactions involving a copper-substituted stereogenic carbon centre

“…loss before C–C bond formation. In this latter scenario, higher allylphosphate concentration should lead to faster alkylation and the loss in kinetic selectivity would be diminished 9 . Indeed, whereas 2g was formed in 64% e.e.…”

“…In the disclosure corresponding to the two-catalyst protocol 2 there is no mention of allyl–boron additions to electron-rich aryl alkenes or those involving more hindered (e.g., 2-substituted) electrophiles. Furthermore, enantioselective Cu–B(pin) or Cu–H additions with electron-deficient aryl olefins are either not mentioned 4,5,6,7,8 or found to be less enantioselective 9,10,11,12 (e.g., halo-, trifluoromethyl- or ester-substituted). It is unclear why enantioselectivity is lower with some substrates or at times depends on electrophile identity despite the fact that the Cu–B(pin)/Cu–H addition step is the stereochemistry-determining (e.g., 94% e.e.…”

“…Conversely, an electron-rich olefin likely generates a more reactive Cu-alkyl species slowly. It has been surmised 9 that some kinetic enantioselectivity might be lost if an organocopper intermediate were to react slowly, whereas rapid trapping, for example with higher electrophile concentration, could improve e.e. The central question then is: exactly how does enantiomeric purity of a Cu-alkyl intermediate erode, and is the dearth of examples with strongly electron-rich and electron-deficient alkenes tied to these issues?…”

Access to Enantioenriched Organosilanes from Enals and β‐Silyl Enones: Carbene Organocatalysis

“…Chiral organosilanes have interesting properties because of the presence of as ilicon having ap articular physical and electronic nature,and they have attracted increasing attention in recent years.Inparticular,chiral organosilanes are used in organic synthesis, [1] materials science, [2] agroscience, [3] and medicinal chemistry. [4] Considerable effort has been devoted to this field, and many elegant catalytically asymmetric approaches for the synthesis of chiral organosilanes have been successfully developed, including asymmetric hydrosilylation of alkenes and alkynes, [5] asymmetric silicon hydride bond insertions, [6] desymmetrization of silanes, [7] asymmetric addition to b-silyl unsaturated carbonyls, [8] and asymmetric silyl conjugated addition. [9] Notably,m ost of the aforementioned methods have rely on transition metals as catalysts.In contrast, an organocatalyzed approach for the synthesis of chiral organosilanes has not been well explored.…”

“…and enantioselectivity (99 % ee)w hen the more sterically hindered aminoindanolderived triazolium pre-catalyst B [16a] was used. Next, several bases were investigated, with Cs 2 CO 3 proving to be the best choice (entries [2][3][4][5][6][7][8]. Subsequent solvent screening revealed that 1,4-dioxane was the most effective,thus providing access to 3a in up to 98 %yield without any loss in d.r.oree values (entries [9][10][11][12].…”