Thioaldehydes synthesis

Vallee Y., Ripoll J. L. Synthesis of Thioaldehydes, Thioketones and Thioketenes... 

Usually these heteroaldehydes and heteroketones are generated in solution in the presence of suitable substrates and immediately trapped. The synthesis, properties, and reactivity of thioaldehydes and thioketones have been the subject of several reviews.1-5 The chemistry of selenocarbonyl compounds has likewise been reviewed in recent years.6-9... 

The synthesis of the thioaldehyde complex 63 somewhat paralleled the synthesis outlined in Scheme 17. In this case, sulfur and hydrogens were transferred to the vinylidene ligand in a single step [Eq. (14)].187... 

Complexes with a bridging vinylidene ligand were also used as the starting compound for the synthesis of thioaldehyde complexes. Sequential treatment of 104 with cyclohexene sulfide, HBF4, and Li[BHEt3] gave the thioaldehyde complexes 105 [Eq. (24)].209... 

These adducts easily undergo cycloreversion reactive unstable thioaldehydes can thus be conveniently stored and recovered, and their chemistry has been greatly developed over the last 10 years, mainly by Vedejs and Kirby [126, 253]. Vedejs elegantly used the thiopyranic heterocycles, via a [2,3] sigmatropic shift of a sulfur ylide [508], as precursors for medium sulfide rings, applied to the synthesis of complex natural products in the cytochalasin-zygosporin family [522, 523] for instance. 

As for thioaldehydes, the stability of thioketenes is largely influenced by the nature of the substituents and bulky groups tend to stabilize this functional group. Electronic factors such as those originating in silicon, phosphorus or trifluoromethyl substituents lead to a similar result. In general, however, the synthesis of monomeric thioketenes is difficult and requires the use of special techniques such as FVT, matrix isolation at low temperatures or generation under conditions which allow trapping in situ of the transient species. The... 

The problem of the synthesis of thioaldehydes has been partly circumvented in recent years by using silyl thioketones as their synthetic equivalents. This clever methodology was introduced by Italian chemists and they have successfully exploited many different applications of these compounds, which have been reviewed by Bonini249. In this... 

Only one isolated example of formation of thioketene and thioaldehyde dimolybdenum complexes has been reported507, but in contrast, zirconocene thioacetaldehyde and thiobenzaldehyde complexes, introduced by Buchwald, have been the subject of several studies508, including their application in the synthesis of novel antimony thiametallacy-cles 148509 (equation 156). Compound 146 was generated in situ and, after reaction with alkynes, gave rise to metallacycles 147 which, by treatment with SbCR, afforded 148. 

Further examples of the photolytic generation of thioaldehydes from phenacyl sulfides include the synthesis of 3,6-dihydro-27/-thiopyrans bearing a variety of functions at C-2 of which some are potent acyl-CoA-cholesterol acyl-transferase inhibitors (Equation 135) <1996BMC1493>. 

The Comprehensive Organic Functional Group Transformations series includes up-to-date overviews of the synthesis of thioaldehydes and thioke-tones [12], thionoesters [13], dithioesters [14], and thioamides [15, 16]. 

A novel synthesis of a-unsaturated sulfines has been introduced by Bra-verman et al. [99]. Et3N or DABCO treatment of allylic and benzylic tri-chloromethyl sulfoxides triggered the elimination of chloroform and formation of the sulfines. It must be stressed that these sulfines are thermally relatively stable, and this stands in high contrast to the corresponding thio-carbonyl compounds unsaturated thioaldehydes cannot be monitored under the same experimental conditions and have to be used at very low temperature or trapped in situ. The first synthesis of thioacrolein S-oxide was achieved by flash vacuum thermolysis of an anthracene allyl sulfoxide [100], and both isomers in a (Z E) ratio of 78 22 were characterised by NMR spectroscopy at -60 °C. 

Heating these products (endo and exo mixtures) was also a source of thiocarbonyl compounds, by cycloreversion [213], and led, in the presence of a diene, to different adducts (exo rich equilibrium mixtures). These reactions were applied in the field of morpholine alkaloids and thioshikimic acid synthesis [5]. Another effective source of thioaldehydes are sulfenyl phthalimides [214], which are very prone to elimination, as described hereunder in the work of Capozzi. 

Thioaldehydes as heterodienophiles in the synthesis of morphine alkaloids 93PS(74)17. 

Finally, a thia Diels-Alder reaction representing a less common cycloaddition type in natural product synthesis shall be discussed. Thus, Vedejs et al. have included such a cycloaddition into an elegant strategy aimed at the synthesis of macrocyclic [ll]-cytochalasans such as zygosporin E 7-76 [536-538]. Thus, release of the thioaldehyde 7-73 from its phenacyl sulfide precursor in the presence of the silyloxydiene 7-74 yielded 7-75 as 2 1 mixture with its C20 epimer. Fortunately, equilibration of this mixture raised the ratio up to 10 1. Several subsequent steps yielded the tetracyclic intermediate 7-77 cleavage of its thioether moiety then liberated the 11-membered macrocycle present e.g. in zygosporin E 7-76 (Fig. 7-16). 

The mechanism of penicillin biosynthesis from the Arnstein tripeptide, 8-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV), has been extensively studied and reviewed by many chemists. Most of the biosynthetic mechanisms have been ascertained by Baldwin and Bradley using an excellent enzymatic technique.55 However, the first step in the biosynthesis of penicillin, conversion of the Arnstein tripeptide to a cis-P-lactam intermediate, is still a fascinating mechanistic problem. Although Baldwin et al. recently proposed a mechanism involving an iron-bound thioaldehyde formation route via a Pummerer-type cyclization, the intermediate for this mechanism has not been identified. The mechanism of selective formation of the cw-P-lactam ring is still also unknown (Fig. 39).56 These types of biomimetic reactions have been chemically studied. An example of an unsuccessful intramolecular Pummerer cyclization of the sulfoxide involving a cysteine moiety under standard Pummerer conditions was reported by Wolfe et al.57 Although Kaneko reported the conversion of the very simple 3-phenylsulfinyl propionamide into a P-lactam with TMSOTf/triethylamine,58 a successful biomimetic synthesis of... 

Scheme 5.20. Synthesis of thio sugars from thioaldehydes and DHAP. Pase = phosphatase.

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