Carbonyl complexes thioacetals

The carbonyl of aldehydes and ketones can be transformed into a gem-difluoro group. This transformation can be performed either directly with DAST or in an indirect manner by treating the corresponding thioacetal or hydrazone with an oxidant (NBS, dibromohydantoin, etc.) in the presence of a source of fluoride ions (e.g., HF-pyridin complex or TBABF prepared from TBAF and KHF2). ... 

Peptide aldehydes constitute a rather general example of protease inhibitors. The electrophilic carbonyl group is attacked reversibly by the cleaving nucleophile, forming a covalent acetal or thioacetal intermediate. With cysteine proteases the preferred inhibitors are strong electrophiles, for example ketones, chloromethyl ketones, epoxides, or vinyl sulfones. Many cysteine protease inhibitors form an enzyme-inhibitor complex irreversibly these are therefore denoted suicide-inhibitors . 

Step II. The "planar" acetate (or thioacetate moity of the ACh (or ASCh) forms a "tetrahedral" complex with the attacking nucleophile methanol as the hybridi-2 zation of the substrate carbonyl carbon changes from sp to sp. ... 

The reduction of Cp2TiCl2 with Mg in the presence of P(OEt)3 affords the titanium(n) complex Cp2Ti[P(OEt)3]2 which was used as a catalyst for the carbonyl olefination of thioacetals through a titanium-alkylidene intermediate (see Section 4.05.4.2.4 alkylidene complexes).1148... 

Dithioacetals, 1,3-dithianes or 13-dithiolanes are prepared by reaction of the corresponding carbonyl compound in the presence of an acid catalyst (cone. HQ, Lewis acids such as Znh, BFs EtaO, TMS-Cl, etc.) with a thiol or dithiol. Silica gel treated with thionyl chloride was found to be an effective as well as selective catalyst for thioacetalization of aldehydes. Thioacetalization can also be achieved using a (polystyryl)diphenylphosphine-4odine complex as a catalyst Conversion of aldehydes or acetals into 1,3-dithianes is achieved with the aid of organotin thioalkoxides and organotin triflates or with 2,2-di-methyl-2-sila-l,3-dithiane. Direct conversion of carboxylic acids to 1,3-dithianes can be carried out by reaction with 1,3,2-dithiabomenane-dimethyl sulfide and tin(II) chloride or 1,3,2-dithiaborolene with trichloromethyllithium followed by basic hydrolysis. 

One of the most versatile procedures for the olefination of carbonyl compounds utilizes a thioacetal-titanocene(II) system [40, 92]. The organotitanium species generated by the desulfurization of thioacetals with the triethyl phosphite complex of titanocene(II) 44 react with a variety of multiple bonds, such as those of alkenes [93], alkynes [94], and nitriles [95], as well as carbonyl functions. The reactivities observed in these reactions indicate that the active species involved are titanocene-alkylidene complexes 48 (Scheme 4.40). 

As described in the previous section, a-elimination of dialkyltitanocenes is of limited use for the preparation of titanocene-alkylidenes. Since thioacetals are readily available from carbonyl compounds or through alkylation of bis(phenylthio)methane and related organosulfur compounds, a thioacetal-titanocene(II) system enables the use of different types of carbene complexes. Use of appropriate thioacetals is of crucial importance in this system for the preparation of alkylidene complexes 48, the corresponding diphenyl thioacetals are the starting materials of choice. No carbene complexes are formed from dialkylthio-acetals. To generate vinylcarbene complexes 49, trimethylene thioacetals of aji-unsaturated aldehydes or l,3-bis(phenylthio)propene derivatives are employed (Scheme 4.41). The low-valent titanium species 44 is also easily prepared by the reduction of titanocene dichloride with magnesium in the presence of triethyl phosphite at room temperature. The presence of molecular sieves 4A is essential for the reproducibility of this preparation. In relatively large-scale preparations, care should be taken to control the reaction temperature [92, 93g]. 

The carbene complexes thus prepared can be employed for the olefination of a variety of carbonyl compounds. The procedure is operationally simple treatment of the thioacetals with titanocene(II) species at ambient temperature for 5-15 min affords the organotitanium species, which are further treated with ketones and aldehydes in the same reaction vessel to give the olefins or dienes (Table 4.12) [96]. 

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