A- thioaldehydes

The radical formed in reaction (8.144) then decomposes to form an alkyl radical and a thioaldehyde molecule that is,... 

When a,/3-unsaturated esters are the target molecules, the use of a thioaldehyde or thioketone is advisable for the easy elimination of H2S from the intermediate thiol adduct. This strategy has been applied to thiolactams 94a and to thionolactones 94b, opening a route to vinylogous carbamates 95a143 and carbonates 95b144(equation 57). 

The regiochemistry of the Diels-Alder reaction of a thioaldehyde depends on the nature of the substituent directly linked to the sp2-carbon atom [175]. 

A thioaldehyde complex (93) was formed, although in very poor yield (<1%), when the l,3-dithiolane-2-thione complex 92 was deprotonated with LDA at low temperature, treated with CS2, and finally alkylated with [Et30]BF4 [Eq. (19)]. No reaction took place in the absence of CS2. Studies using 14C-labeled CS2 confirmed that CS2 was incorporated into the complex.62... 

The reaction is of great value and most of the early work in the field is quoted and discussed in [203] by Block. As the allyl vinyl sulfide can be metallated and submitted to electrophilic substitution prior to rearrangement and the thiocarbonyl group hydrolysed in situ to a carbonyl group in the reaction product, the process has found considerable utility. The syntheses of propylure [488] and ris-jasmone [489] are early examples in which a thioaldehyde was intermediary formed (Y = H). A thioketone was involved [490] in the rearrangement of the allyl allenyl sulfide shown here. 

Fluorinated thioketones <1965JOC1390> and perhalogenoalkylthioacetyl fluorides <1992CB1889> are reactive dienophiles and rapidly add across the 9,10-bond of anthracene to form the isothiochroman nucleus 494 (Equation 170). Similar products result from the treatment of the sulfenyl chloride 495 with triethylamine when a thioaldehyde is generated (Scheme 182) <1991J(P1)3225>. 

Table 3 Indium-mediated allylation of a-thioaldehydes. Reproduced with permission from ACS Publications...

In the a-elimination mechanism (39) as shown in Equation 9, hydrogen extraction by the base alpha to the sulfur results in formation of a carbanion which may rearrange via route a or b c to give cysteine and a thioaldehyde which decomposes in alkaline solution to an aldehyde and hydrogen sulfide. Thus, the stoichiometry of this reaction is (Equation 10) ... 

A general route to thioaldehydes is the base-induced 1,2-elimination of sulfenate derivatives, described initially by Kirby et al. In this reaction, phthalimide derivatives, e.g. (25), react with Et3N to generate a thioaldehyde, which is subsequently trapped by dimethylbutadiene to yield product 26 [83CC423 85JCS(Pl)1541]. Other dienes used in this study include thebaine, cyclohexadiene and anthracene. 

Kirby and co-workers obtained alkyl thioxoacetate, which was trapped by a diene to give a Diels-Alder adduct, e.g. 30. When this adduct was heated at 110°C in the presence of a new diene, a retro Diels-Alder reaction took place. The thioaldehyde thus generated gave a new adduct, 31. Adduct 30 is, therefore, a thioaldehyde transfer reagent [85JCS(P1)1541]. 

A plausible intermediate for the enantio- and diastereoselective addition of diethylzinc to a-thioaldehyde catalyzed by 20o is shown in Fig. 3-4. When 20o ((—)-DFPE) is used in the ethylation of the racemic aldehyde 41, the (li)-enantiomer reacts faster than the (5)-enantiomer and the newly produced stereogenic center from (P)-41 has the S-configuration. This stereochemical property can be reasonably explained by considering the 7/6-fused bicyclic intermediate depicted. Compound (P)-41 has lower steric hindrance than (S)-41 in the reaction complex and ethylzinc preferentially attacks from the Si face of (7 )-41 to afford the S-configuration. Therefore, (i )-41 reacts faster than (S)-41 to afford (3S,4R)-42. 

Thiolsulfonates decompose thermally according to first-order kinetics with the production of sulfides, sulfur dioxide, hydrocarbons and other products resulting from secondary decompositon of a thioaldehyde... 

The thioketene dimetallic complex 493 reacts with H to give an anionic thioacyl complex (494). Protonation of494, by cleavage of a metal - carbon bond, gives a thioaldehyde complex (495) which is stabilized by PPhj... 

Lactam Antibiotics.—A wealth of detail is now available on the fates of individual carbon and hydrogen atoms of valine (150) and cysteine (152) on transformation into the penicillins [as (151)]. It has been confirmed recently that cysteine gives penicillin with loss of the 3-pro-S hydrogen and it was pointed out that if oxidation of the C-3 thio-group to say a thioaldehyde occurs in the course of biosynthesis, then... 

Couture showed that methyl- and dimethylthiophene on irradiation in a primary amine gave pyrroles and proposed a mechanism where the first step is the formation of a thioketone or a thioaldehyde by analogy with furan photochemistry (Scheme 2).7... 

This transformation undoubtedly occurs via a retro-Diels-Alder reaction of 10 to give a thioaldehyde. 

Considering all of these observations, a possible mechanism for this interesting biochemical reaction is shown in Figure 26. Central to this proposed mechanism is the involvement of a persulfide (R-S-SH), a thioaldehyde and a protein-bound disulfide in the proposed reaction mechanism. Persulfides are known to be widely involved in the biosynthesis of many important sulfur containing metabolites. Here they function as a protein-bound nucleophilic sulfur that can add to an aldehyde and be reductively released from the protein to form the thioaldehyde (reactions 2-3, Figure 26). The persulfide could be formed by the transfer of hydrogen sulfide to a disulfide (reaction 1, Figure 26). 

The known occurrences of thioaldehydes in biochemistry are few. One well-studied example is the involvement of a thioaldehyde in the decarboxylation of cysteine in phosphopantothenoyl-cysteine during coenzyme A biosynthesis. In the proposed mechanism for this decarboxylation, a thioaldehyde is generated at the cysteine sulfur by a flavin-dependent oxidation of the thiol. The resulting /3-thioketo acid, acting like a /3-keto acid, facilitates the decarboxylation of the amide-bound cysteine in phosphopantothenoyl-cysteine substrate. Finally, the flavinH2 produced in the thiol oxidation is used to reduce the thioaldehyde back to the thiol. 

A significant feature is the shielding of the aromatic protons, indicating a 7t-excessive character for this system. As can be seen in Table 5, when the 5-position is substituted by a thioaldehyde function, H-3 is significantly deshielded by the anisotropic current of the thiocarbonyl group. 

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