2-Oxetanones synthesis

More stable alternatives to ketene that have been used in 2-oxetanone synthesis are (trimethylsilyl)ketenes 100 <1996CC1053>. Using methylaluminoimidazolines as catalysts, with aldehydes and 100, 3-(trimethylsilyl)oxetan-2-ones (101a and 101b) were generated with up to 83% ee (Equation 36). 

Oxetanone, 3,3,4,4-tetramethyl-solvolysis, 7, 380 2-Oxetanone, 4-trichloromethyl-decarboxylation, 6, 374 dehydrochlorination, 7, 374 structure, 6, 366 2-Oxetanone, 3-trimethylsilyl-synthesis, 7, 395... 

Methods for the synthesis of optically active (3-lactones (2-oxetanones) 99T6403. 

The existence of ketenes was established over a hundred years ago, and, in recent years, asymmetric synthesis based on [2 + 2] cycloadditions of ketenes with carbonyl compounds to form chiral p-lactones has been achieved with high yields and high stereoselectivities. In 1994, Miyano et al. reported the use of Ca-symmetric bis(sulfonamides) as ligands of trialkylaluminum complexes to promote the asymmetric [2 + 2] cycloaddition of ketenes with aldehydes. The corresponding oxetanones were obtained in good yields and enantioselectivities... 

This general strategy has been employed for the synthesis of several types of heterocycles, including diketopiperazines [29-32], ketopiperazines [29, 33], pyrro-lidinones [34], 1,4-benzodiazepines [29, 32, 35-37], dihydroquinoxalinones [29], hexahydropyrrolodiazepines [38], and oxetanones [27]. Figure 4 shows some selected examples. 

A very promising synthesis of /3-lactones has been recently reported, involving the palladium-catalyzed carbonylation reaction of halogeno alcohols. For example, 3-phenyl-2-oxetanone was obtained in 63% yield from 2-phenyl-2-bromoethanol in DMF solution at room temperature under 1 atmosphere pressure of carbon monoxide (equation 115). A proposed mechanism, in which palladium metal inserts into the carbon-halogen bond, followed by insertion of a molecule of carbon monoxide into the carbon-palladium bond and then ring closure, fits kinetics data (80JA4193). 

Chiral compounds (Continued) epoxy alcohols, 141 formulas, xiii xvii hydroxystannanes, 318 liquid crystals, 350 molecular lattics, 347 natural, 1 NMR spectra, 282 olefins, 173 oxetanones, 326 phenols, 287 see also Binaphthol phenylbutenes, 172 protonating agents, 324 sulfoxides, 159 sulfur ylides, 328 synthesis, I... 

In the present review the ring systems containing one heteroatom are considered first, except for P-lactams which are given a special section at the end. Interest in azetidines continues to be stimulated by the discovery of the potentially useful trinitro derivative. The requirements for the stereoselective synthesis of substituted oxetane are being explored and derivatives of aluminium are useful in the stereoselective routes to oxetanones. The preparation and subsequent pyrolysis of oxetanones is suggested as an alternative to the Wittig route to olefins. Stereoselective routes to thietanes and thietane 1 -oxides are mentioned. 

The aldol (23) on treatment with benzenesulphonyl chloride yields the oxetanone ((3-lactone) (24) which is an intermediate in the synthesis of the butenolides (25) (95SC479). Aliphatic terminal alkynes or arylalkynes react with nitrones in the presence of a copper based catalyst system to give 1,3,4-trisubstituted [3-lactones (95JOC4999). 

The structure, synthesis and biological activity of natural 2-oxetanones and their derivatives has been reviewed (95S729). The synthesis of some novel 3-(hydroxymethyl)-4-(2-substituted ethyl)-2-oxetanones and their biological activity as 3-hydroxy-3-methyl-glutaryl coenzyme-A inhibitors has been reported (94CPB1272, 94CPB2097). 

While diketene remains a very important synthetic precursor, there has been increasing interest in the chemistry of a-methylene-/3-lactones, 3-methylene-2-oxetanones. However, unlike diketene, which can be readily synthesized by the dimerization of aldehydic ketenes, there are few methods for the synthesis of a-methylene-/3-lactones in the literature. Recent strategies for the preparation of the compounds are discussed in Section 2.05.9.2. The kinetic resolution of racemates of alkyl-substituted a-methylene-/3-lactones has been carried out via a lipase-catalyzed transesterification reaction with benzyl alcohol (Equation 21) <1997TA833>. The most efficient lipase tested for this reaction was CAL-B (from Candida antarctica), which selectively transesterifies the (A)-lactone. At 51% conversion, the (R)-f3-lactone, (R)-74, and (A)-/3-hydroxy ester, (S)-75, were formed in very high enantio-selectivities (up to 99% ee). 

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