1.3- dicarbonyl compounds sulfide

Finally, the Hinsberg synthesis has been extended to the use of a-aryl-a-carboethoxydimethyl sulfide in conjunction with a series of 1,2-dicarbonyl compounds. Specifically, the 4-nitroaryl substituent provides for sufficient activation of the a-proton to allow condensation and ring closure. These examples appear general and suggest future opportunities for the Hinsberg thiophene protocol. 

Benzothiepins 2 can be synthesized by a double Knoevenagel condensation starting from phthalaldehydes I and diesters of thiodiglycolic acid, or diphenacyl sulfide.33-63 " 66 In principle, this is an extension of Hinsberg s synthesis of thiophenes (see Houben-Weyl, Vol. E6a, p 282) which employs 1,4-dialdehydes rather than 1,2-dicarbonyl compounds. 

This procedure illustrates a broadly applicable method which is essentially that of Roth, Dubs, Gotschi, and Eschenmoser,2 for the synthesis of enolizable /1-dicarbonyl compounds. Although there are various methods for the preparation of /3-dicarbonyl systems,3 the scheme of sulfide contraction widens the spectrum of available methods. The procedure can also be utilized in the synthesis of aza and diaza analogs of /3-dicarbonyl systems. Eschenmoser2 has utilized the method to produce vinylogous amides and amidines in connection with the total synthesis of corrins and vitamin B12.4... 

Reaction of 1,3-dicarbonyl compounds with vinyl sulfides gives the corresponding medium- and large-sized ring substituted furans 78 in moderate to good yields. In addition to cyclohexane-1,3-diones, 4-hydroxycoumarins and 4-hydroxyquinone can also be used as 1,3-dicarbonyl components . 

This is often achieved from 1,4-dicarbonyl compounds in a procedure similar to that used to form furans but using phosphorus pentasulfide, or Lawesson s reagent (see below), to cause a transposition from carbonyl to thiocarbonyl groups, prior to cyclization and loss of hydrogen sulfide (Scheme 6.37). 

The synthesis of 4//-thiopyrans from 1,5-dicarbonyl compounds consists of the cyclization of 1,5-dioxo precursors with hydrogen sulfide in the presence of protic acids or with various phosphorus polysulfides. 

Ring closure of 1,4-dicarbonyl compounds with phosphorus sulfides (Paal synthesis) 884... 

Sequential addition of hydrogen sulfide to an a,/3 -unsaturated ketone, followed by condensation with an a -dicarbonyl compound, leads directly to thiophenes. Thus addition of hydrogen sulfide to a benzene solution of cyclohexenone, followed by an a -dicarbonyl compound and reflux, gave the respective 6,7-dihydro-5//-benzo[6]thiophene-4-ones (274). Compounds were obtained by this method where R1 and R2 = H, R1 = Ph or Me and R2 = H, and where R1 = R2 = Me (71lJS(A)(i)62). This is closely related to a patented process previously described (cf. Section 3.15.3.4). 

AH- Thiopyrans are directly accessible only in relatively poor yield, and then only by condensation of a suitable 1,5-dicarbonyl compound with sulfide (690PP21). As has been described earlier, this particular reaction is bedevilled with the problem of disproportionation to tetrahydrothiopyrans and thiopyrylium compounds. Thiopyran-4-ones may be prepared in a related manner by addition of sulfur dichloride to divinyl ketones, followed by base treatment (76MI22500). 

Unsaturated 1,5-dicarbonyl compounds. The phenylthioalkylation of silyl enol ethers of carbonyl compounds (9, 521-522) can be extended to the synthesis of unsaturated 1,5-dicarbonyl compounds. In a typical reaction the enol silyl ether of a ketone is alkylated with the unsaturated chloride 1 under ZnBr2 catalysis to give a homoallyl sulfide. Ozonolysis of the methylene group is accompanied by oxidation of the phenylthio group sulfoxide elimination results in an unsaturated 1,5-aldehydo ketone (equation I). Alkylation with 2 results in a methyl ketone (equation II). 

Maillard reaction products formed by interaction of reducing sugar and amino acids such as a-dicarbonyl compounds, aldehydes, hydrogen sulfide, and ammonia can react further to form derivatives that have been identified from meat or its components during heating. Important reviews of sulfur compounds that might be produced by these reactions have been published by Schutte (35) and... 

This important flavor compound was identified in the head-space volatiles of beef broth by Brinkman, et al. (43) and although it has the odor of fresh onions, it is believed to contribute to the flavor of meat. This compound can be formed quite easily from Strecker degradation products. Schutte and Koenders (49) concluded that the most probable precursors for its formation were etha-nal, methanethiol and hydrogen sulfide. As shown in Figure 5, these immediate precursors are generated from alanine, methionine and cysteine in the presence of a Strecker degradation dicarbonyl compound such as pyruvaldehyde. These same precursors could also interact under similar conditions to give dimethyl disulfide and 3,5-dimethyl-l,2,4-trithiolane previously discussed. 

In many examples, it is not necessary to prepare the phosphorane. Instead, the dicarbonyl compound is heated with a trialkyl or triaryl ester of phosphorus acid or, less commonly, with a diester of a phosphonous acid (RP(OH)2, where R is an organic group). For example, when the thioester 301 is heated with dipropyl ethylphosphonite the 2-substituted carbapenem 302 is produced in 80% yield (Equation 32) <1997CPB1439>. This general method has been used to prepare 2-sulfide-substituted 1/3-methylcarbapenems <2000CPB126, 2001SC587> and O-protected 2-hydroxymethyl derivatives < 1999JA11261 >. 

Another interesting group of heterocyclic compounds formed in the reaction of 2,4-decadienal and cysteine is the thiophenes. Thiophenes having butyl to heptyl groups substituted at the 2-position were identified. Mechanisms have been suggested for the production of thiophene derivatives by the action of hydrogen sulfide on 1,4-dicarbonyl compounds (24). The exact mechanism for the formation of thiophenes in this system is not clear and deserves more study. 

Fig. 8 Iron-catalyzed coupling reactions of P-dicarbonyl compounds with ethers, sulfides or tertiary amines...

Li and coworkers published addition reactions of ethers, sulfides, or tertiary amines 40 to p-dicarbonyl compounds 39 (Fig. 8) [96]. Fe2(CO)9 proved to be the catalyst of choice and di-tert-butyl peroxide the optimal oxidant. a-Functionalized p-dicarbonyl compounds 41 were isolated in 52-98% yield. Although the details of the catalytic cycle remain unclear, it seems to be likely that the peroxide is reductively cleaved by the Fe(0) catalyst leading to an Fe(I) complex and a ferf-butoxyl radical, which abstracts the a-hydrogen atom of 40. Addition of the resulting radical to the free enol form of 39 or the corresponding iron enolate of 39 may subsequently occur. It remains unclear, however, whether the main catalytic reaction proceeds on an Fe(0)-Fe(I) oxidation stage or whether further oxidation of initially formed Fe(I) rather leads to an Fe(II) catalyst. This cannot be excluded,... 

In the oxygenation of 5,6-dihydro- 1,4-oxathiin 116, despite the presence of allylic hydrogens and the sulfide moiety, the sole reaction product is the dicarbonyl compound 118 (isolated yield 90%) [126a] deriving from the corresponding dioxetane 117, which has been spectroscopically... 

Reaction of a four-carbon unit with sulfur sources such as hydrogen sulfide, carbon disulfide, and elemental sulfur is one of the traditional thiophene syntheses that belong to this category (Equation 18). A wide variety of hydrocarbons, for example, alkanes, alkenes, dienes, alkynes, and diynes, serve as four-carbon units. Another practical method is the sulfuration of 1,4-dicarbonyl compounds (Paal synthesis). The method has become very popular with development of sulfuration reagents such as Lawesson s reagent. The reaction of a,/3-unsaturated nitriles with elemental sulfur in basic media, Gewald synthesis, is also useful for the preparation of 2-aminothiophenes which are important compounds in dyestuff and pharmaceutical industries. 

Interaction of 1,2-Dicarbonyl Compounds with Ethers or Sulfides. 842... 

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