DiTOX

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

The intensification of studies of the derivatives of sterically hindered ligands such as OCR3 [where R = Ph, Bu (tritox)],OCHBu2 (ditox), OSiR3, 2,6-or 2,4,6- substituted phenoxides RnC6HJ.nO (where R= Me, Pr, Bu, Ph) is... 

The most numerous are their adducts with THF, PR3, Py and other amines of 2,6- and 2,4,6-substituted phenols and also the derivatives of the most branched radicals Ditox, Tritox, CPh3) CjHuneo, CMeB(CF3)3 , and so on. These molecular compounds — monomers or dimers — have been described for... 

Fig. 2. Molecular structures of Nd(tritox)3(NCCH3)2 [38] and Dy(ditox)3(NCCH3)2 [39]...

The Ln(tritox)3 system underlies a thermal degradation reaction (Sect. 6.3). Attempted sublimation yielded Ln(ditox)3, the dimeric composition of which... 

The sterically most congested CH-alkoxides Ln(tritox)3 is thermally labile and decomposes to Ln(ditox)3 by loss of isobutene [29, 38]. In addition, a small quantity of di-terf-butylketone indicates the formation of a Ce(III) hydride species. Ln(ditox)3 can be obtained in analytically pure form via sublimation. Scheme 44 describes the mechanistic scenario which was suggested for the Ce(tritox)3 system [29]. 

However, with the significantly smaller thulium formation of the ditox derivative is observed upon attempted sublimation [40], In addition, use of the slightly less bulky proditox ligand affords a thermally stable and sublimable Y(proditox)3 [39]. Obviously the thermal lability of the Ln(tritox)3 is caused by... 

The dithiane 1-oxide (DiTOX) moiety (2) fulfills the following criteria for an ideal chiral auxiliary ... 

DiTOX and its 2-substituted derivatives are readily prepared, generally stable, and relatively inexpensive. 

DiTOX systems are amenable to stereoselective preparation for both sulfoxide enantiomers. 

The DiTOX system has been shown to induce high levels of stereoselectivity for a range of reaction types based on carbonyl group reactivity. 

The DiTOX auxiliary can be readily removed, in high yield, without loss of stereochemical integrity at the newly created asymmetric center(s). 

Unless otherwise stated, racemic 2-acyl-2-alkyl-DiTOX derivatives were used as substrates for the applications described in this review. The preparation of enan-tiomerically pure 2-acyl-2-alkyl-DiTOX systems are described in a subsequent section. 

For the syn substrate 8, the approach of the organometallic nucleophile is controlled by the steric bias imposed by the bulky DiTOX ring (Fig. 2). The nucleophile approaches the prochiral carbonyl group from the direction of the... 

Structure 15 shows the product of DIBAL reduction of 5y/i-2-propionyl-2-methyl-l,3-dithiane 1-oxide (entry a, Table 2), and 16 shows the product of DIBAL/ZnCl2 reduction of a/ifi-2-propionyl-2-isopropyl-DiTOX (entry 1, Table 2). 

Table 5. Mannich Reaction of Enolates of 2-Propionyl-2-ethyl DiTOX Substrates Using Eschenmoser s Salt as Aminoalkylating Agent...

We aimed to develop facially selective Diels-Alder reactions using our DiTOX methodology such methodology has been the goal of many research groups, and several useful chiral auxiliaries have been developed to accomplish this aim.53... 

Perkin ring synthesis using DiTOX. Anions derived from DiTOX undergo efficient Perkin ring synthesis on treatment with dihaloalkanes to provide cycloalkane rings of up to seven members (Table 12).59... 

Table 12. Perkin Ring Synthesis Using DiTOX...

Asymmetric sulfoxidation of2-acyl-1,3-dithianes Preparation of optically pure DiTOX substrates. The preliminary investigations of 1,3-dithiane derivatives as asymmetric building blocks and chiral auxiliaries described in this review... 

Several approaches to the enantioselective oxidation of sulfides have been reported,61 including enzymatic approaches,62 use of optically pure oxidants,63 and several modifications of the Sharpless epoxidation procedure.63,64 The success of these procedures is somewhat substrate dependent for example, dialkyl sulfides and more complex substrates can give unpredictable results. 1,3-Dithiane itself is oxidized with only ca. 20% ee optically pure DiTOX has, however, been obtained by resolution.65... 

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