Epoxide with organometallic

Ring Opening of Epoxide with Organometallics [54] (C6Hi3)2CuCNLl2... 

The reaction of alkenyl epoxides with organometallic species (lithium, magnesium, copper, and boron) affords allylic alcohols, following an Sn and/or Sn mechanism. These processes can accommodate only little organic functionality and exhibit low regio- and/or stereoselectivity. Under smooth conditions, C—C bond formation proceeds by nucleophilic alkylation of vinyl epoxides in the presence of catalytic amounts of zerovalent palladium. Regio- and stereoselectivity can be achieved via the formation of a Tr-allylpal-ladium complex. Trost and Molander and Tsuji and co-workers simultaneously reported the first studies in 1981. Since then, numerous papers have dealt with this subject. Essentially, after chelation and oxidative addition of the palladium onto the vinyl epoxide, the zwitterionic 7r-allylpalladium complex deprotonates the nucleophile, which can in principle attack either carbon 2 (proximal attack) or 4 (distal attack) (Scheme 1). 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

Metalated epoxides can react with organometallics to give olefins after elimination of dimetal oxide, a process often referred to as reductive alkylation (Path B, Scheme 5.2). Crandall and Lin first described this reaction in their seminal paper in 1967 treatment of tert-butyloxirane 106 with 3 equiv. of tert-butyllithium, for example, gave trans-di-tert-butylethylene 110 in 64% yield (Scheme 5.23), Stating that this reaction should have some synthetic potential , [36] they proposed a reaction pathway in which tert-butyllithium reacted with a-lithiooxycarbene 108 to generate dianion 109 and thence olefin 110 upon elimination of dilithium oxide. The epoxide has, in effect, acted as a vinyl cation equivalent. 

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-... 

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

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. 

The rate also decreases with an increase in the chain length of the alkene molecule (hex-l-ene > oct-1-ene > dodec-l-ene). Although the latter phenomenon is attributed mainly to diffusion constraints for longer molecules in the MFI pores, the former (enhanced reactivity of terminal alkenes) is interesting, especially because the reactivity in epoxidations by organometallic complexes in solution is usually determined by the electron density at the double bond, which increases with alkyl substitution. On this basis, hex-3-ene and hex-2-ene would be expected to be more reactive than the terminal alkene hex-l-ene. The reverse sequence shown in Table XIV is a consequence of the steric hindrance in the neighborhood of the double bond, which hinders adsorption on the electrophilic oxo-titanium species on the surface. This observation highlights the fact that in reactions catalyzed by solids, adsorption constraints are superimposed on the inherent reactivity features of the chemical reaction as well as the diffiisional constraints. 

Payne rearrangement. The Payne rearrangement2 of a primary cts-2,3-epoxy alcohol to a secondary 1,2-epoxy alcohol usually requires a basic aqueous medium, but it can be effected with BuLi in THF, particularly when catalyzed by lithium salts. As a consequence, the rearrangement becomes a useful extension of the Sharpless epoxidation, with both epoxides available for nucleophilic substitutions. Thus the more reactive rearranged epoxide can be trapped in situ by various organometallic nucleophiles. Cuprates of the type RCu(CN)Li are particularly effective for this purpose, and provide syn-diols (3).3... 

Asymmetric microbial oxidation afforded the (-)-epoxide which has been explored as a building block ring opening reactions with organometallic nucleophiles, and via Friedel-Crafts reactions have been reported. [226,227]. A non-biotransformative approach to this epoxide has also been described [228]. Copper(II)-catalysed oxidative hydrolysis (Eq. 72) affords a lactic acid analogue in high enantiomeric purity [229]. 

Liquid-Phase Epoxidation with Hydroperoxides. Molybdenum, vanadium, and tungsten have been proposed as liquid-phase catalysts for the oxidation of the ethylene by hydroperoxides to ethylene oxide (205). tert-Butyl hydroperoxide is the preferred oxidant. The process is similar to the arsenic-catalyzed route, and includes the use of organometallic complexes. 

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. 

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>. 

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