4- oxetan-2-ones, synthesis

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

Ethenediyl carbonate (l,3-dioxol-2-one vinylene carbonate, 417) is a readily available,270 versatile synthon having pronounced dienophilic properties.270-275 Diels-Alder adducts of 417 with 1,4-di-acetoxy-1,3-butadiene and furan were selectively converted into cy-clitols,256 257-275 and also served as precursors of DL-ribose derivatives258 (see Section IV, 2). Another possibility of applying 417 as an equivalent of a 1,2-dihydroxyethane unit has been demonstrated in a synthesis of racemic apiose. Photochemical cycloaddition of 417 to 1,3-diace-toxy-2-propanone (418) gave the oxetane derivative 419, which, on alkaline hydrolysis, afforded DL-apiose (420) in 23% yield.1... 

Mildly basic to neutral conditions for the ring closure of 1,3-halohydrins include tetra-phenylantimony methoxide as an effective non-basic reagent for oxetane synthesis from 1,3-bromohydrins (90S106). The salts of (3-halo acids cyclize in ionizing media to oxetan-2-ones, as do (3-diazonium carboxylates (64HC(l9-2)787). Thietanes are obtained analogously. 

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. 

Oxetanes have also been synthesized by the immobilization of 2,2 -disubstituted 1,3-diols with polymer-bound sulfonyl chloride, followed by intramolecular cyclization/cleavage from the solid support (Scheme 17) <2005TL643>. One percent divinylbenzene (DVB) cross-linked polystyrene and polyethylene glycol (PEG) (average Mn 3400) were used as polymer support in this reaction, and in both cases the properties of the polymer support allowed rapid purification of the intermediate. Intermediates on the insoluble cross-linked polystyrene support could be washed with a range of organic solvents to remove insoluble impurities, whereas the soluble PEG supported products could be purified by recrystallization from isopropanol. This is thought to represent the first reported polymer-supported synthesis of oxetanes. 

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). 

The intramolecular nudeophilic substitution reaction - for example, the William-son-type reaction - represents one of the important methods for preparing oxetane ring structures, and have been widely applied to the synthesis of oxetanes (Scheme 7.1) [10]. Unfortunately, side reactions - which indude fragmentation from the intermediary alkoxide anion or elimination from the intermediary carboca-tion - often decrease the chemical yields of oxetane formation. 

The photochemical reaction of carbonyl compounds and alkenes, which is referred to as the Paterno-Buchi (PB) reaction, was developed in 1909 [13], and is currently one of the most widely used methods for oxetane synthesis (Scheme 7.4). As exemplified in the PB reaction of benzophenone with 2-methylpropene [14], a selective formation of the oxetane is possible even when the photochemical reaction involves highly unstable molecules that is, the excited state of carbonyls. Due to its synthetic importance and mechanistic interest, the PB reaction is the most extensively studied synthetic method for oxetanes. Thus, several extensive reviews describing the PB reaction have been published since 1968, and the reader is directed towards these for further information [15]. In this chapter, methods that allow for the control of the regioselective and stereoselective formation of synthetically important oxetanes will be described. 

The synthesis of fused oxetane derivatives via the Paterno-Bchi cycloaddition of carbonyls and alkenes is discussed in detail in a representative example is shown in Scheme 7 <2001CEJ4512>. See also Sections 3.3.1.8.3 and 3.4.1.10.5 for the preparation of fused oxetanes and azetdines by [2 + 2] cycloaddition reactions. Benzox-etan-2-one 10 has been prepared in an argon matrix by C02 loss from phthaloyl peroxide <1973JA4061>. 

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

One of the key steps used in a new synthesis of the bis(tetrahydrofuran) moiety of Asteltoxin (94) is the photoaddition of the propanal (95) to 3,4-dimethylfuran, yielding the adduct (96). This cycloaddition is a common outcome of the irradiation of aldehydes or ketones with furans. An analogous adduct (97) results from the photoreaction of butyl glyoxalate with 2-methylfuran. Two other products [(98) and (99)] are also formed, the first of which is presumably the result of ring opening of the isomeric oxetane (100), while (99) is produced by a hydrogen abstraction radical coupling pathway. 

The hetero [2+2] cycloaddition reaction is a synthetically important reaction for the construction of 4-membered heterocyclic compounds. As far as the catalytic asymmetric reaction is concerned, however, only the cycloaddition between ketenes and aldehydes has been reported. The thus synthesized chiral oxetan-2-ones are employed as monomer precursors for the biologically degradable co-polyesters and also as chiral building blocks for natural product synthesis. Two types of catalysts. Cinchona alkaloids and a chiral Lewis acid, are known to promote this reaction. 

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