Epoxides with organometallic reagents

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

Aziridines have been opened by organometallic reagents to give amines. Although less reactive than epoxides, it is also possible to open aziridines with organometallic reagents. Isopropylmagnesium chloride reacts with A-tosyl 2-... 

In contrast with the behaviour of typical vinylphosphonic acid derivatives, the carbon-carbon double bond in the 1,2-oxa-phospholene (167) is remarkably unreactive towards a broad spectrum of reagents including electrophiles, most epoxidizing and organometallic reagents, as well as to dipolar addition reactants. Exceptional reagents are, however, N-bromoacetamide (NBA), ozone, dimethyllithiumcuprate, and sodium-naphthalene. 

Copper-catalyzed asymmetric allylic alkylations with organometallic reagents used for small-ring openings, such as epoxides and aziridines, have gained interest. Illustrating... 

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 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. 

For lists of organometallic reagents that react with epoxides, see Wardell, J.L. Paterson, E.S. in Hartley Patai. The Chemistry of the Metal-Carbon Bond, vol. 2 Wiley NY, 1985, p. 307 Ref. 568, p. 512. 

For a list of organometallic reagents that react with vinylic epoxides, with references, see Ref. 568, p. 123. 

Preparation of alcohols Organometallic reagents (RMgX, RLi) are powerful nucleophiles. They attack epoxides at the least hindered carhon, and generate alcohols. For example, propylene oxide is an unsymmetrical epoxide, which reacts with methyl magnesium bromide to produce 2-butanol, after the acidic work-up. 

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

Few types of epoxide react with Grignard or organolithium reagents in the absence of catalysts without rearrangement. These include oxirane, which has been extensively used to transform these organometallic reagents into 2-substituted... 

C—C Bond formation with allylmagnesium chloride. J. Org. Chem. 1997, 62, 9342—9344. Overman, L. E. Renhowe, P. A. Regioselective opening of terminal epoxides with 3-(trialkyl-silvljallvl organometallic reagents. J. Org. Chem. 1994, 59, 4138-4142. 

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