Epoxides protocols

While asymmetric approaches are certainly important, other synthetically significant epoxidation protocols have also been reported. For example, buffered two-phase MCPBA systems are useful for epoxidations in which the alkenes and/or resultant epoxides are acid-sensitive. Bicarbonate works quite well for cinnamate derivatives (e.g., 55) <96SC2235> however, 2,6-di-t-butyl-pyridine was shown to give superior results in the case of certain allyl acetals (e.g., 57) <96SC2875>. 

A recent synthesis of the phenylisoserine side-chain of taxol is shown in Scheme 18. The enone 21 was obtained in high yield by condensation of benzal-dehyde with pinacolone. Employing the non-aqueous two-phase epoxidation protocol, epoxide 22 was obtained in 76% yield and 94% e.e. Recrystallisation of the epoxide furnished the desired enantiomer in 97 % e. e. Subsequent manipulations of the epoxy-ketone gave the taxol side-chain 23 with the required stereochemistry (Scheme 18). 

With a twist on the Sharpless asymmetric epoxidation protocol, Yamamoto and co-workers <99JOC338> have developed a chiral hydroxamic acid (17) derived from binaphthol, which serves as a coordinative chiral auxiliary when combined with VO(acac)j or VO(i-PrO)j in the epoxidation of allylic alcohols. In this protocol, triphenylmethyl hydroperoxide (TiOOH) provides markedly increased enantiomeric excess, compared to the more traditional t-butyl hydroperoxide. Thus, the epoxidation of E-2,3-diphenyl-2-propenol (18) with 7.5 mol% VO(i-PiO)3 and 15 mol% of 17 in toluene (-20 °C 24 h) provided the 2S,3S epoxide 19 in 83% ee. 

DIBAH reduction of 4 at -78 °C provides the corresponding trans-allylic alcohol. Successive epoxidation with meto-chloroperbenzoic acid (MCPBA) yields a single syn epoxide 5. The stereochemical assignment is proven by a second experiment using the asymmetric Sharpless epoxidation protocol. Both MCPBA and the Sharpless protocol using (-)-diethyl D-tartrate provided 5. 

The high a-selectivity is based on the absence of neighbor group participation. Protection of sugar 5 with acetyl groups and using the same epoxidation protocol leads to a 1 1 a ft mixture of the epoxides. 

In regard to aziridine synthesis, there are two basic strategies of comparable importance, namely (1) the addition of an amine component onto some C2 fragment such as an olefin, or (2) the addition of a Ci component onto a C-N substrate such as an imine (Scheme 2, Paths A and B, respectively). The former approach bears at least conceptual similarity to the classical olefin epoxidation protocols, yet exhibits significant mechanistic differences. 

In addition to the fact that the reagent s ingredients are commercially available, the reaction is promiscuous and proceeds in good chemical yield with excellent enantiomeric excesses. The reaction, however, does suffer when bulky substituents are cis to the hydroxymethyl functionality (R in Figure 1). For prochiral alcohols, the absolute stereochemistry of the transformation is predictable, whereas for a chiral alcohol, the diastereofacial selectivity of the reagent is often sufficient to override those preferences inherent in the substrate. When the chiral atom is in the -p-position of the allyl alcohol (R ), then the epoxidation can be controlled to access either diastereoface of the alkene. In contrast, when the chirality is at either the a- or Z-P-positions (R or R ), the process is likely to give selective access of the reagent from only one of the two diastereotopic faces [6,12]. Many examples of substrates for the epoxidation protocol are known [1,13,14]. 

Terminal olefins represent another challenging substrate class. For olefins such as styrene, cis-trans partitioning leads to diminished catalyst enantioselec-tivity (60-70% ee). A viable solution was reported through an efficient low-temperature Mn(salen) epoxidation protocol employing N-methylmorpholine N-oxide and ra-CPBA [77]. Improved enantioselectivities were attainable for most substrates under low-temperature conditions, but the effect was especially pronounced in the case of terminal olefins. Epoxidation of styrene, for instance, occurred rapidly to afford the epoxide in 86% ee using catalyst 22g (Scheme 8). Deuterium-labelling experiments revealed that the improved enantioselectivity derived from enhancement of olefin facial selectivity in initial C-0 bond formation as well as suppression of deleterious cis-trans partitioning. 

In particular, the AE reaction on cis-substituted alkenes, which normally tend to give lower enantioselectivities, resulted in excellent ees employing catalyst 3. In addition, this epoxidation protocol tolerates the use of aqueous TBHP, and does not suffer from the ligand deceleration effects normally observed for vanadium catalysts. 

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