Sulfur derivatives Diels-Alder reactions

Perfluorotetramethylthiadiphosphanorbornadiene and bis(trifluoromethyl) thiadiphosphole can be prepared by thermolysis of an adduct of methanol and hexakis(trifluoromethyl)-l,4-diphosphabarrelene with sulfur [113] (equation 23) Pyrolysis of the adduct of hexafluorinated Dewar benzene and phenyl azide results in ring expansion giving azepine, which photochemically yields an intramolecular 2-1-2 adduct, a good dienophile for the Diels-Alder reaction [114, //5] (equation 24) Thermolysis of fluonnated derivatives of 1,5-diazabicyclo-... 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

The chemistry of thienoquinolines has been explored to a limited degree. Two types (378,379) will be described in this subsection. The pharmacological interest in thieno[2,3-Z>]quinoline (378) and derivatives thereof stems from their isosteric and isoelectronic resemblance to acridine furthermore, (378) constitutes the sulfur analog of furoquinoline (Section 3.17.2.1.5), which is the parent system of a number of alkaloids. Thieno[3,4-6]quinoline (379) is an o-quinonoidal heterocycle which is of interest both for theoretical reasons compared with its isoconjugate analogues and as a synthon in Diels-Alder reactions for the preparation of other condensed heterocycles. 

Thiophene reacts with alkynes to give the corresponding benzene through a photochemical Diels-Alder reaction followed by extrusion of a sulfur atom (Scheme 9) (72TL1909 73CB674). Thienyl derivatives with electron withdrawing substituents allow adducts isolation (78CJC1970). 

However, 2-nitrothiophene (176), but also 2-acetylthiophene and thio-phene-2-carbaldehyde, irradiated in the presence of phenylacetylene, gave the corresponding diphenyl derivative ortho substituted 177. The reaction is probably a photo Diels-Alder reaction with extrusion of sulfur from the adduct to give the observed product (95TL6567). 

Extrusion of sulfur dioxide from a ring-fused dihydiothiophene derivative provides an exceptionally easy method for the preparation of heterocyclic o-dimethylene compounds. These compounds are valuable intermediates in intermolecular Diels-Alder reactions. This extrusion method was used to prepare the o-dimethylene compounds 44-46 <95CC1349> as well as quinolinone derivative 47 <95TL5983>. TTie dihydrothiophene dioxide moiety also played an important role in the formation of the intramolecular Diels-Alder reaction of N-substituted pyrrole 48 <95CC807>. 

The reaction of 3-substituted triazolo[4,5- ]pyrimidines (8-azapurines) (213) with activated methylene synthons in the presence of sulfuric acid is reported to afford 5,6-disubstituted triazolo[4,5-i]pyridines (215). Since these reactions occur via 5-amino-4-formyltriazoles (214) (79CPB2861, 88BSCB85), similar cyclizations of other derivatives of 5-amino-4-formyltriazole have afforded additional analogues (Table 12) <73JCS(P1)1620>. Higashino and co-workers have also shown that 3//-triazolo[4,5- ]pyrimidines (213) participate in an inverse-electron Diels-Alder reaction with enamines (216) to afford the derivatives (215), albeit in low yields (Schemes 40 and 41) <91CPB282>. 

As in Explanation 89, these two compounds do not react in the sense of the Diels-Alder reaction. Instead, a cyclobutane derivative is formed by cycloaddition. The reaction is a free-radical process starting with single electrons on carbons 1 and 2 of perfluorovinylsulfur pentafluoride. Carbon 1 of the 1,3-butadiene joins the difluoromethylene group of the perfluorovinylsulfur pentafluoride because in this way, the newly formed biradical can better accommodate the single electron on the carbon next to the SF5 group. The biradical closes the ring in such a way that two stereoisomers, P and Q, cis- and trans-2,3,3-trifluoro-l-vinyl-2-cyclobutyl-sulfur pentafluoride, are formed in equal amounts [122]. 

Scheme 3. The highly-ordered transition state associated with the Diels-Alder reaction has made it a natural target for work in the field of catalytic antibodies [15]. Indeed, Hilvert [15a] has reported recently the first successfully antibody-catalyzed Diels-Alder reaction. Monoclonal antibodies elicited to the boxed hapten 14 provided both acceleration of and multiple turnover of the cycloaddition between tetrachlorothiopene dioxide and IV-ethyl maleimide. The initial adduct decomposes by the chelotropic-extrusion of sulfur dioxide affording the dihydrophthalimide derivative 13...

In the study of S3 sources, the interaction of the tetrathiocine 36 with norbornene yielded a mixture of the thiophene 37 and 3,4,5-trithiatricyclodecane 38 the products were derived from sulfur extrusion by the retro-Diels-Alder reaction and sulfur trapping, respectively (Equation 9) <2004JA9085>. 

Middleton established that reaction of 1,2-dialkylhydrazines with sulfur and reduction of sulfinylhydrazines (R2N—N=S=0) with lithium aluminium hydride yielded highly colored N-thionitrosoamines (95), which are stable at < ca. -30°C (66JA3842). However, it was deduced from spectroscopic data that these were not true RN=S species a high contribution from the dipolar resonance form accounts for their stability. Nonetheless, compound 95 will act as a 277 component in an inverse electron demand Diels-Alder reaction with a tetrazine derivative to yield triazole 96 (79CZ230). 

Stereoselective Diels-Alder reactions have been reported in several cases. Enantioselective Diels-Alder reactions of l-phenoxycarbonyl-l,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using a chiral cationic palla-dium-phophinooxazolidine catalyst afforded chiral isoquinuclidines with excellent enantioselectivity <2005TL5677>. Bismuth(lll) chloride-mediated diasteroselective intramolecular [4-f2] cycloaddition reactions of A-allyl derivatives of pyrazole aldehydes led to fused sulfur-containing pyrazole heterocycles <2003SC3063>. A highly diastereoselective intramolecular hetero-Diels-Alder approach toward tetracyclic pyrazoles from 5-(3-methyl-2-butenylthio)-3-methyl-l-phenyl-4-pyrazolecarboxaldehyde has been reported <1997SL1155>. 

---