1 ,3-Enynes Epoxides

The lithium etiolate of acetaldehyde DMH has recently been utilized in the opening reaction of the ot-epoxide obtained by DM DO oxidation ofenol ether 142, to provide hemiacetal 143 after mild oxidative acid hydrolysis. The protected carbonyl functionality was subsequently used for the introduction of the trans enyne chain through a Wittig olefmation reaction to provide alcohol 144, which was then transformed into (+)-laurenyne (Scheme 8.37) [71]. 

Cao et al.102 extended their discovery to the asymmetric epoxidation of enynes using ketone 130 as the catalyst and Oxone as the oxidant (Scheme 4-50). 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

One of the subunits of the natural product (-)-macrolactin A, a strong anti-viral agent, has been synthesized as shown in the following scheme, involving the hydrotelluration of a enyne (a), and the opening of an epoxide with a vinylic higher-order cyanocuprate (b). ... 

Styrenes [103], conjugated aT-dienes [107], and aT-enynes [108] are also epoxidized with ketones 57 in high ees (Table 5, entries 9-14). No isomerization of the epoxides was observed therefore only c/x-epoxides were obtained from cis-olefins. Alkenes and alkynes appear to be effective directing groups to favor the desired transition states T and V (Fig. 19). 

Fig. 19 The competing transition states for the epoxidation of dienes and enynes...

Asymmetric epoxidation of conjugated dienes and enynes catalysed by the chiral man-ganese(EI) complex 232 give monoepoxides exclusively reactions of cw-enynes give /raw.v-alkynyl epoxides as the major products with a high level of asymmetric induction362. 

Indeed, these epoxide-facilitated ring closure reactions show advantages over other methods. For example, Clive and Magnuson were able to access a desired tricyclopentanoid intermediate 79 for the synthesis of ( )-ceratopicanol by the Cp2TiCl-mediated cyclization of the bicyclic epoxide 78. Attempts to construct this system through conventional enyne radical cyclizations yielded only the bridged product (i.e., 81) [95TL15]. 

Asymmetric Epoxidation of Representative Conjugated Dienes and Enynes by Ketone 1... 

Liu has reported recently a new Co2(CO)8-mediated tandem [5+ 1]/ [2 + 2+ 1]-cycloaddition reaction that gives tricyclic 5-lactones from cis-epoxy enynes 186. This process possibly involves an initial opening of the epoxide in the cobalt hexacarbonyl complex 187 to from the complexed al-lene 189 via 188. Further coordination of the tethered olefin leads to 190 and further oxidative cyclization gives cobaltacycle 191 which inserts CO leading to the final compound 192. When performing the reaction under N2,191 suffers a reductive elimination to give cyclobutane 193 (Scheme 55) [172],... 

Other post-PKR processes that may happen are oxidation reactions in those cases in which final PK products may liberate part of their strain by adding water or epoxidizing the emerging double bond [195,196]. These results appear under oxidative reaction conditions (using N-oxides as promoters), as in the synthesis of medium sized rings from certain aromatic enynes, where small amounts of epoxides were obtained [28]. 

Of course, one could also think about opening the epoxide 33 with lithium acetylide to the enyne 38, which could eventually be further reacted by Trost s method (e.g. with the vinyl bromide 27). 

An iterative sequence of propargylation, enantioselective epoxidation of the resulting silylated skipped enynes, an endo selective hydroxyepoxide cyclisation and protodesilylation in which a SiMes group plays a pivotal role produces the tris-tetrahydropyran 9 in 18 steps <03OL2339>. The stereoselectivity of the endo selective oxacyclisations of 1,4-di- and... 

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