Yang epoxidation, ketones

Yang D. Ketone-catalyzed asymmetric epoxidation reactions. Acc. Chem. Res. 2004 37 497-505. 

General experimental procedure for Yang epoxidation with ketone 55 To a mixture of olefin (1 mmol), ketone 55 (0.1 mmol),... 

In 1996 Yang and coworkers reported a series of binaphthyl-derived -symmetric ketones (8) as epoxidation catalysts (a few examples are shown in Fig. 2)[32-34],... 

In 1998, Yang and coworkers reported a series of (7 )-carvone derived ketones (63) containing a quaternary center at and various substituents at (Fig. 22) [119]. The ees of fran -stilbene oxide varied with different para and meta substituents when 63b was used as the catalyst. The major contribution for the observed ee difference is from the n-n electronic repulsion between the Cl atom of the catalyst and the phenyl group of the substrate. The substitution at also influences the epoxidation transition state via an electrostatic interaction between the polarized C -X bond and the phenyl ring on franx-stilbene (Table 6, entries 3-7, 10-14). In 2000, Solladie-Cavallo and coworkers reported a series of fluorinated carbocyclic ketones... 

The breakthrough came already in 1996, one year after Curd s prediction, when Yang and coworkers reported the C2-symmetric binaphthalene-derived ketone catalyst 6, with which ee values of up to 87% were achieved. A few months later, Shi and coworkers reported the fructose-derived ketone 7, which is to date still one of the best and most widely employed chiral ketone catalysts for the asymmetric epoxidation of nonactivated alkenes. Routinely, epoxide products with ee values of over 90% may be obtained for trans- and trisubstituted alkenes. Later on, a catalytic version of this oxygen-transfer reaction was developed by increasing the pH value of the buffer. The shortcoming of such fructose-based dioxirane precursors is that they are prone to undergo oxidative decomposition, which curtails their catalytic activity. 

Chiral dioxirane that was also generated in situ from the corresponding ketone and Oxone was first used for catalytic asymmetric epoxidation by Curd et al., although enantioselectivity was low [7], Later, Yang et al. disclosed that this approach had a bright prospect if used with a combination of Oxone and chiral ketone 3 [8]. Ketone 3 is converted into the corresponding dioxirane in situ, which epoxidizes olefins (Scheme 6B.5). 

Chiral ketone catalysts of the Yang-type (5a and 5b, see above) and of the Shi-type (10, Scheme 10.2) have been successfully used for kinetic resolution of several racemic olefins, in particular allylic ethers (Scheme 10.4) [28, 29]. Remarkable and synthetically quite useful S values of up to 100 (ketone 5b) and above 100 (ketone 10) were achieved. Epoxidation of the substrates shown in Scheme 10.4 proceeds with good diastereoselectivity. For the cyclic substrates investigated with ketone 10 the trans-epoxides are formed predominantly and cis/trans-ratios were usually better than 20 1 [29]. For the linear substrates shown in Scheme 10.4 epoxidation catalyzed by ketone 5b resulted in the predominant formation of the erythro-epoxides (erythro/threo-ratio usually better than 49 1) [28]. 

Yang ( / /. have investigated a series of C 2-symmetric chiral ketones based on the 2,2-bis(diphenyl-phosphanyl)-l,l-binaphthyl (BINAP) skeleton. The asymmetric epoxidation of phenylcyclohexene (and in one example dihydronaphthalene) was achieved in good yields and levels of enantioselectivity (Figure 12) <1996JA491, 1998JA5943, 2004ACR497>. 

Yang et al. have applied C2-symmetric chiral dioxiranes, generated in situ from corresponding chiral ketones 75 and Oxone, for asymmetric epoxidation of trans-olefins and trisubstituted olefins (33-87% ee) <1996JA491, 1996JA11311>. 

Yang s chiral ketones 75 have also been used as catalysts in the kinetic resolution of acyclic secondary allyl silyl ethers <2001JOC4619>. Dioxiranes generated in situ from dehydrocholic acid derivatives 122 and Oxone have been used in the asymmetric epoxidations of cinnamic acid derivatives with product ee s up to 95% <2001TA1113, 2002JOC5802> and unfunctionalized olefins (up to 98% ee) <2006T4482>. 

Shi and co-workers reported in 1996 the enantioselective epoxidation of unfunctionalized alkenes mediated by the fructose-derived ketone 10 (Figure 10.10) [46]. Corresponding oxiranes were obtained with excellent enantioselectivities (Equation 10.23). Yang and co-workers also reported the enantioselective epoxidation of alkenes, employing a cyclic ketone derived from binaphthyldicarboxylic add [47]. 

Recently, exceptional progress has been made in the development of chiral ketones (via dioxirane intermediates) based on asymmetric epoxidations (Eq. 3.10). Although the first such type of asymmetric epoxidation was carried out by Curci in 1984, it is only in the last decade that excellent enantioselectivity of such epoxidations has been achieved. Two of the most prevalent workers in the area are Shi " (by using chiral sugar-based ketone, 3.4) and Yang (chiral binapthalene derivative, 3.5). Often, these reactions are performed by using Oxone in an aqueous environment. Many other chiral ketones have also been developed and these methods have been used in various syntheses. This subject has been reviewed by many authors. ... 

The pioneering work by Curd offered one of the first examples of the use of chiral catalysts in the asymmetric epoxidation of alkenes with Oxone. In this early example the use of chiral ketone (-l-)-isopinocamphone (3, Figure 19.1) afforded low enantioselectivities (<15% ee) and reaction rates in a biphasic solvent system [9]. Subsequently, Yang developed a class of C2-symmetrical ketones 4 that in a monophasic (CH3CN/H2O) solvent system gave improved enantioselectivity [47% ee for the epoxidation of ( )-stilbene] [10, 11],... 

In 1996, Yang and co-workers reported on a C2-symmetric chiral binaphthyl ketone 54 as an efficient catalyst for the asymmetric epoxidation of unfunctionalized olefins. In ketone 54, a remote binaphthalene unit was used as the chiral control element to make the catalytic center less hindered, and the electron-withdrawing esters at the a-carbon made ketone 54 very reactive (Figure 35.7). High conversion and moderate-to-good enantioselectivity for the epoxidation of tra i-disubstituted olefins and trisubstituted olefins can be obtained with as low as 5 mol% of catalyst 54... 

Yang D, Yip YC, Tang MW, Wong, MK, Zheng JH, Cheung KK. A C-2 symmetric chiral ketone for catalytic asymmetric epoxidation of unfunctionalized olefins. J. Am. Chem. Soc. 1996 118(2) 491 92. 

In 1998, Yang and coworkers reported a ketone with a quaternary carbon at the a-position at one side and a substituent at the fi-position of the other side of the carbonyl group (75) (Scheme 3.54) [88]. Studies on a series of meto- and para-substituted trons-stilbenes with 75b showed that the ee of the epoxide varied with the substituent... 

In their studies, Yang and coworkers also showed that a spiro transition state was favored for the ketone 9 catalyzed epoxidation, see refs. [11, 12]. 

In 1996 Yang first reported the asymmetric epoxidation of olefins mediated by a symmetric dioxirane generated from the corresponding ketone [22]. The chiral ketone was derived from BINAP, and exhibited enantioselectivities typically between 5% and 50% ee under stoichiometric conditions, and 87% ee in the epoxidation of trans-4,4 - diphenylstilbene. With modification of the original C2 symmetric ketone and development of the reaction to run catalytically, Yang was able to increase the enantioselectivity of the process [23, 24], With very hindered alkenes, such as frans-4,4 -diterf-butylstilbene, enantioselectivities of up to 95% ee were achieved (Scheme 1.9). 

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