Ethers diphenylprolinol

For a recovery of (S)-a,a-diphenylprolinol, which is the hydrolysis product of the CBS-catalyst (S)-5 (and likewise its synthetic precursor ), the aqueous phase is carefully adjusted to pH 10 with concentrated ammonia and extracted with diethyl ether (3 x 50 ml). The combined organic layers are washed with brine (50 mL) and dried over MgS04. Removal of the solvent by rotary evaporation yields 1.68 g (79%) of crude (S)-a,a-diphenylprolinol. This material is dissolved in dichloromethane / methanol 9 1 (3 ml) and filtered over Alox B (act. Ill, 80 g) with dichloromethane / methanol 9 1 as the eluent, to yield 1.64 g (77%) of (S)-a,a-diphenylprolinol as a white solid. 

Diphenylprolinol methyl ether catalyses the enantioselective Michael addition of simple aldehydes to simple enones.219... 

Diphenylprolinol silyl ethers (17) have been found to be efficient organocatalysts for the asymmetric Michael reaction of aldehydes and nitroalkenes. 

Diphenylprolinol methyl ether (145) catalyses intermolecular Michael addition of simple aldehydes to enones in the absence of solvents with high enantioselectivities (95-99% ee) and significantly lower catalyst loadings (5 mol%) than have been typical in this arena.175... 

The diphenylprolinol silyl ether 45a catalyst was developed by the Hayashfs group for the addition of a-unbranched aldehydes to aryl and alkyl substituted nitroolefins [35]. This catalyst, as well as the perfluoroalkyl derivative 45b [36],... 

Chi Y, Gellman SH (2005) Diphenylprolinol methyl ether a highly enantioselective catalyst for Michael addition of aldehydes to simple enones. Qrg Lett 7 4253 1256... 

Enders et al. elegantly applied diphenylprolinol silyl ether 6a as a catalyst for triple cascade reactions (Scheme 10.18), wherein 6a played the roles ofboth enamine catalyst and iminium catalyst. It should be noted that the four stereocenters were completely controlled[36].Theproposedcatalyticcycleofthe triplecascade isshownin Scheme 10.2. 

Hayashi and co-workers took advantage of the organocatalyzed reaction for the stereoselective synthesis of the cyclohexane structure. Diphenylprolinol silyl ether ent-6a proved to be effective for the domino Michael reaction/Horne-Wardsworth-Emmons reaction. They synthesized (-)-oseltamivir by three one-pot operations, with a total yield of 57% (Scheme 10.4) [38]. 

The (S)-diphenylprolinol-derived oxazabotohdine with an ethanediolated boron atom is a new catalyst for the as3fmmetric reduction of ketones with BH3 SMe2- 1,3-Cyclo-alkanediones undergo CBS-reduction to provide (3if)-hydroxycycloalkanones. Based on this method a very short synthesis of chiral estrone methyl ether is completed. ... 

The triethylsilyl ether of a,a-diphenylprolinol 2B induces the Michael-aldol reaction tandem that combines A -protected o-aminobenzaldehydes and 2-alkenals to form chiral 2-substituted 3 -formyl-1,2-dihydroquinolines. ... 

Screening of other proline-derivatives identified L-diphenylprolinol TMS ether as a superior catalyst, providing access to cyclopropane products in moderate to excellent yields (43-95% yield) and high enantioselectivities (90-98% ee). 

Scheme 7.28 Asymmetric Michael addition of aldehydes with methyl or ethyl vinyl ketones catalysed hy (S)-diphenylprolinol methyl ether.

Cordova " and Wang showed new variants of cyclopropanation reaction using diphenylprolinol silyl ether catalysts. The reaction required... 

The 0-TBS-hydro>y-diphenylprolinol silyl ethers 14, analogues of the Jorgensen-Hayashi catalyst 3a, were tested in 2008 by List and coworkers for the challenging catalytic asymmetric Michael reactions of acetaldehyde with nitroalkenes. While 4-hydroxy-proline derivative 14a displayed diminished activity, but slightly better enantioselectivity with respect to 3a, the 3-hydroxy-proline derivative 14b gave in this case very poor results (Scheme 11.12). 

In 2010, Enders and co-workers developed a quadruple cascade AFC/ Michael/Michael/aldol condensation reaction of indoles, acrolein, and nitroalkenes under the catalysis of diphenylprolinol TMS-ether catalyst (S)-104 following an iminium/enamine/iminium/enamine activation sequence (Scheme 6.42). " The reaction provided a straightforward and efficient entry to 3-(cyclohexenylmethyl)-indoles 105 bearing three stereogenic centers in moderate to excellent yields (23-82%) and excellent stereoselectivity (91 9->95 5 dr and 94->99% ee). 

In 2003, Melchiorre and Jprgensen found modest enantioselectivities in the first catalytic version of the direct enantioselective Michael addition of aldehydes to vinyl ketones catalyzed by the chiral amine (5)-2-[bis(3,5-dimethylphenyl)methyl] pyrrolidine (21) (Scheme 2.13) [34]. Further studies on the reaction carried out by different groups led to more efficient catalysts such as diphenylprolinol ethers 22a [35] and 22b [36] and imidazohdinone 23 [37] (Schane 2.13). The highest enantioselectivities reported to date (95-99% ee) have been obtained with catalyst 22b employing significantly lower catalyst loadings (1-5 mol%) than those reported with other organocatalysts (20-30 mol%)[36]. 

An early example of an asymmetric domino Michael/Knoevenagel reaction was reported by Jorgensen et al. [167] in 2006, providing the synthesis of chiral cyclohexenones from the reaction of tert-butyl 3-oxobutyrate and a, 3-unsaturated aldehydes catalyzed by chiral diphenylprolinol silyl ether derivative. Soon after, the... 

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