Epoxides terminal, from aldehydes

MacMillan et al. developed a SOMO-activation protocol for the stereoselective a-chlorination of aldehydes and for the formation of terminal epoxides starting from aldehydes (317). This method was employed recently by the Christmann... 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Oxidations. Aromatic aldehydes are obtained by oxidation catalyzed with a Mn(IV) complex. A procedure for oxidation of alcohols which is organic solvent free and halide free employs 30% H Oj, Na2W04 dihydrate, and a quaternary ammonium hydrogensulfate. Under such conditions secondary alcohols are oxidized 4-5 times faster than primary alcohols. In toluene the conversion of benzylic alcohols to aldehydes or acids (depending on quantities of HjOj) is accomplished. A similar system is also effective for epoxidation of alkenes. Terminal epoxides are obtained in reactions mediated by a Mn(II) complex or Mg-Al-O-t-Bu hydrotalcite. The last catalyst is capable of inducing epoxide formation from other alkenes and enones. 

In 2008, Connon and coworkers reported a base-mediated protocol for the S3mthesis of terminal epoxides from aldehydes and trimethylsulfonium iodide utilising 5 mol% of urea analogue 9. Electron-rich and electron-deficient aromatic aldehydes were well tolerated providing the corresponding products in moderate to high yields. In the case of cycloheigrl carboxaldehyde, an increase in the reaction time was required. It has to be... 

Photo-catalytic bromination of epoxides derived from terminal alkenes results in the formation of ketones brominated exclusively on the less substituted a-carbon atom [equation (47)]. 5,5-Dibromo-2,2-dimethyl-4,6-dioxo-l,3-dioxan (32) has been shown to monobrominate saturated aldehydes and ketones... 

Cuzzola et al. have studied, using ionspray and electrospray MS and SPME-GC-MS, the Fenton oxidation products of surfactants such as lauryl sulfate [90] and AES [91]. The oxidation leads to the formation of products with hydroxyl and epoxide groups because of insertion of oxygen atoms or aldehydes [90] or terminal ethoxylic moieties [91] derived from the loss of the hydrophilic sulfate group. 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

Evidence of variables that influence the relative rates of reaction of olefins and alcohols was obtained from experiments with compounds that have both olefinic and alcoholic functions and by the competitive oxidation of mixtures of olefins and alcohols. The data of Table VI show that when the double bond has no substituents, as in allyl alcohol, but-3-en-l-ol, or 2-methylbut-3-en-l-ol, only the epoxide is formed but when the double bond has substituents, the epoxida-tion rate is decreased and ketone and aldehyde products from the oxidation of the OH group are formed. This effect is more pronounced with a greater degree of substitution. Since the double bond and the OH group are part of the same molecule, the difference must arise from the different abilities of the reactants to coordinate and react at the titanium center restricted transition-state shape selectivity is a possibility. The terminal double bond, sterically less hindered, interacts strongly with titanium, preventing coordination of the competing OH... 

The synthetic application of the a-chloro aldehydes has been demonstrated by the preparation of a variety of important chiral building blocks (Scheme 2.35) [26b]. The a-chloro aldehydes could be reduced to the corresponding optically active a-chloro alcohols in more than 90% yield, maintaining the enantiomeric excess by using NaBFU. It was also shown that optically active 2-aminobutanol - a key intermediate in the synthesis of the tuberculostatic, ethambutol - could be obtained in high yields by standard transformations from 2-chlorobutanol. Furthermore, the synthesis of an optically active terminal epoxide was demonstrated. The 2-chloro aldehydes could also be oxidized to a-chloro carboxylic acids in high yields without loss of optical purity, and further transformations were also presented. 

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