Organometallic reagents reaction with epoxides

The methyl group is delivered syn to the epoxide via an intermediate chelate between the organometallic reagent and the epoxide oxygen. Consistent with this hypothesis is the observation that the civ selectivity is increased as the solvent polarity is decreased and that addition of trimethylaluminum, which can strongly coordinate to the epoxide, gives nearly exclusively the trans-product. In the latter reaction, it was assumed that the addition of methylcopper occurs anti to the chelated epoxide moiety, possibly via an SN2 mechanism20. 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

The Reaction of Organometallic Reagents with Epoxides 3(OCJ-seco-Alkyl-de-alkoxy-substitution... 

To make ethers more reactive, they must be complexed with strong Lewis acids. BF3 is commonly used with cyclic ethers, and even with epoxides it increases the rate and yield of the reaction when organometallic reagents are used as nucleophiles. BF3 is most easily handled as its complex with diethyl ether, written BF3 OEt, BuLi does not react with oxetane, for example, unless a Lewis acid, such as BF3, is added, when it opens the fouremembered ring to give a quantitative yield of H-heptanoI. 

The reaction of terminal epoxides with hindered lithium amide bases followed by organometallic reagents generates alkenes <2004JA12250>. Related reactions are the formation of enamines <2004JA6870> from terminal epoxides, 2-ene-l,4-diols from terminal epoxides <20050L2305>, and allylamines from amino epoxides <20060L349>. 

Because organometallic reagents are strong nucleophiles, they react with many other electrophiles in addition to carbonyl groups. Because these reactions always lead to the formation of new carbon-carbon bonds, they are also valuable in organic synthesis. In Section 20.14, we examine the reactions of organometallic reagents with carbon dioxide and epoxides. 

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