2,3-epoxy alcohols introduced

From a stereochemical point of view, compound 35 is rather complex, for it possesses four contiguous oxygen-bearing stereocenters. Nonetheless, compound 35 is amenable to a very productive retro-synthetic maneuver. Indeed, removal of the epoxide oxygen from 35 furnishes trans allylic alcohol 36 as a potential precursor. In the synthetic direction, SAE of 36 with the (+)-dialkyl tartrate ligand would be expected to afford epoxy alcohol 35, thus introducing two of the four contiguous stereocenters in one step. 

Although the Sharpless asymmetric epoxidation is an elegant method to introduce a specific defined chirality in epoxy alcohols and thus, in functionalized aziridines (see Sect. 2.1), it is restricted to the use of allylic alcohols as the starting materials. To overcome this limitation, cyclic sulfites and sulfates derived from enantiopure vfc-diols can be used as synthetic equivalents of epoxides (Scheme 5) [12,13]. 

The presence of the stereogenic centre at C(l) introduces an additional factor in the asymmetric epoxidation now, besides the enantiofacial selectivity, the diastereoselectivity must also be considered, and it is helpful to examine epoxidation of each enantiomer of the allylic alcohol separately. As shown in Fig. 10.2, epoxidation of an enantiomer proceeds normally (fast) and produces an erythro epoxy alcohol. Epoxidation of the other enantiomer proceeds at a reduced rate (slow) because the steric effects between the C(l) substituent and the catalyst. The rates of epoxidation are sufficiently significative to achieve the kinetic resolution and either the epoxy alcohol or the recovered allylic alcohol can be obtained with high enantiomeric purity [9]. 

The presence of a stereogenic center at Cj of an allylic alcohol introduces an additional factor into the asymmetric epoxidation process in that now both enantiofacial selectivity and dias-tereoselectivity must be considered. It is helpful in these cases to examine epoxidation of each enantiomer of the allylic alcohol separately. Epoxidation of one enantiomer proceeds normally and produces an erythro epoxy alcohol in accord with the rules shown in Figure 6A.1. 

The azido group is introduced by a titanium-mediated nucleophilic opening of 2,3-epoxy alcohol 5 invented by Sharpless.10 In principle, nucleophilic attack at C-2 or C-3 is possible. 

Ring-opening fluorination of 2,3-epoxy-alcohols is one of the most important ways of introducing fluorine atoms into functionalized organic compounds (Scheme 12.12). Sc(OTf)3 could act as an efficient catalyst in ring-opening fluorination of 2,3-epoxyalcohols by ammonium hydrogen fluorides [20]. 

Walsh approached the formation of epoxides with adjacent secondary alcohols through the asymmetric addition of alkylzinc reagents to a,p-unsaturated aldehydes followed by diastereoselective epoxidation (Scheme 4.26) [60]. Aldehyde 132 reacted with Et Zn in the presence of catalyst 133 to yield zinc alkoxide 134. Introducing to the system followed by Ti(OiPr) led to the isolation of epoxy alcohol 135 in high yield and enantiomeric excess and with good diaste-reocontrol. This one-pot process was proposed to occur through the intermediacy of a zinc peroxide that forms upon the addition of to the system. 

Kimura et al. [77] at Eisai developed an enantioselective synthesis of (S)-noremopamil 153, L-type calcium cshannel blocker, by using SAE as key step to introduce chirality (Scheme 9.41). Epoxidation of allylic alcohol 150 gave the crystalline epoxy alcohol 151 in 84% yield (> 99% ee). The epoxide 151 was elaborated into (5)-noremopamil as well as a library of related phenylal-kylamines through the formation of intermediate 152 containing quaternary carbon. 

The hydroperoxy functionality can be introduced into an alkene by a singlet oxygen ene reaction and subsequently reduced quantitatively to an allylic alcohol, by addition of reducing agents such as PPhs, Me2S or NaBHj ". In addition, the allylic hydroperoxides can be transformed stereospecilically in the presence of Ti(OPr-i)4 to an epoxy allylic alcohol, where epoxide and hydroxyl functionalities are cis to each other (e.g. substrate 160, Scheme 58) - . ... 

First let us consider the initiation process in the presence of proton-donor compounds specially introduced into the system. Two contradictory viewpoints about the reaction mechanism may be distinguished in this case. One of them 138,139f l45,154) presupposes a molecular mechanism of the reaction, i.e. a stepwise polyaddition of the epoxy compound to the alcohol group, e.g. according to Scheme (32)... 

Following the successful development of epoxidized soybean oil( 5), mainly as a stabilizer adjuvant with high permanence but poor low temperature plasticizing properties, the epoxidized fatty acid esters were introduced. These included the C8 mono-hydric alcohol esters — octyl epoxystearate and octyl epoxy-tallate. They also acted as stabilizer adjuvants but with outstanding low temperature plasticizing properties. The epoxy stabilizer/plasticizers have grown to over 50,000 tons/year in the U.S. in 1978, with the epoxidized soybean oil type predominating. 

---