B-Allyl-10-Ph-9-borabicyclo[3.3.2]decanes:  Strategically Designed for the Asymmetric Allylboration of Ketones

Abstract

The simple and efficient syntheses of B-allyl-10-(phenyl)-9-borabicyclo[3.3.2]decane (1) in both enantiomeric forms are reported. The remarkable enantioselectivity (81-99% ee) of these reagents in the allylboration process at -78 degrees C is only modestly diminished when the process is conducted at 0 degrees C, a phenomenon attributable to its rigid bicyclic structure. In addition to providing the homoallylic alcohols 6 efficiently (70-92%), the procedure also permits the efficient recovery of the chiral boron moiety (67-82%) as an air-stable crystalline N-methylpseudoephedrine complex 4 for the direct regeneration of 1 with allylmagnesium bromide in ether (98%). The reagent gives predictable stereochemistry, providing a strategically designed "chiral pocket" which is particularly receptive to leading methyl groups (e.g., methyl ethyl ketone, 87% ee).

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…However, similar 10-Ph derivatives react rapidly with ketones to obtain the homoallylalcohols in very good yields and outstanding enantioselection (Table 38, entries 5−8). 98 Particulary noteworthy is the excellent enantioselectivity obtained in the addition to ketones with groups of similar steric demand (Table 38, entry 8). As occurs for aldehydes, quenching the reaction with pseudoephedrine allows the recovery of the chiral reagent.…”

Asymmetric Synthesis of 2°- and 3°-Carbinols via B-Methallyl-10-(TMS and Ph)-9-borabicyclo[3.3.2]decanes

“…To a solution of (+)-4′Sb 6 (1.17 g, 3.0 mmol) in hexane (12 mL), freshly prepared methallylmagnesium chloride (9.0 mL of 0.66 M in THF) was added dropwise. The solution was allowed to stir for 2 h. The reaction mixture was cooled to −78 °C and quenched with 1.0 equiv of TMSCl.…”

Asymmetric Hydroboration of 1,1‐Disubstituted Alkenes

“…[11] The basic scaffold of these reagents was prepared in enantiopure form by ring expansion of Bmethoxy-9-BBN (1) and resolution of 2 to 3, followed by reduction to give the borohydride derivatives 4 (Scheme 2). Hydroboration reactions were subsequently carried out in the presence of one equivalent of Me 3 SiCl to generate the reactive boranes 5 in situ (Scheme 2).…”

“…The nature of the 10-substituent also influences the conformation of the bicycle which subtly influences selectivity in both the hydroboration and allyl/ crotylboration reactions. [11] The intermediate trialkylboranes 11 have also been used as coupling partners in Suzuki-Miyaura reactions with aryl-, heteroaryl-, and vinylbromides thereby extending the utility of the current process (Scheme 4). Compounds 12, where R 1 and R 2 = aryl/heteroaryl represent important pharmacophores in medicinal chemistry which are not easy to prepare in an enantioenriched form.…”