With heterodiene systems

From the synthetic viewpoint, a particularly interesting trifluoroacetylation reaction of simple vinyl ethers was reported first by Hojo et al in 1976 [73] The scope and limitation of this particular reaction were elaborated intensively, the reaction proved to be of general applicability with practically no restrictions on substituents of the vinyl ether moiety 9] (equation 34) This general validity is particularly beneficial because a trifluoroacetylated vinyl ether is the synthetic equivalent of a specifically protected tnfluoromethyl-substituted 1,3-dicarbonyl compound 19], thus the reaction provides access to a broad spectrum of variously substituted synthetic building blocks with selective reactivities on each carbon acceptor (a) and donor (d) center (equation 35) Obviously, such building blocks can react as heterodiene systems m cycloaddition reactions [< 74] or can be treated with a wide variety ot 1,2 or 1 3-dinucleophihc species to give any desired tnfluoromethyl-substituted carbocychc or heterocyclic system [8 75] Treatment of simple vinyl ethers with an excess of trifluoroacetic anhydride at elevated temperature leads to doubly acylated products [76] Comparable acylation reactions occur with vinyl thioethers [73], and the mesoiomc l,3-oxathiol-4-ones show, at least in a formal sense, similar behavior [77] (equation 36)... 

Of particular interest is the reaction of 9 with the acid chloride 109 from which the [2 + 4] cycloaddition product 110 is isolated. In this compound the aromatic ring supplies two of the 4 r-electrons of the formal heterodiene system (equation 21)117. 

Although the heterodiene system N=C—C=N is usually unreactive toward the addition of benzyne (see also Section VI, A), compounds containing the system C=N—N=C will react with benzyne in a 1,4-cycloaddition, which is followed by extrusion of the azo bridge as nitrogen. This pattern of... 

Heteroarylthiols react quickly with conjugated azoolefins to afford a-heteroarylthiohydrazones by the usual 1,4-addition of the thiol to the heterodiene system. The treatment of the latter compounds with sodium methoxide, and then with trifluoroacetic acid provides mainly regioisomeric 4-heteroarylthio-l//-pyrazol-5(2f/)-ones in good yields by an heterocyclization process with the loss of an alcohol molecule. These reactions can be succesfully executed in a one-pot procedure (Scheme 12). A detailed iH- and J3c-NMR study of these compounds in OMSO-d shows a solvent effect on the enol-keto tautomerism, often with conversion of the keto into the enol form. X-Ray diffraction determination demonstrates unambiguously that these compounds exist in... 

DAB 155a-c and 2,3-DAN 235 on the terminal carbon of the heterodiene system of 1,2-diaza-l,3-butadienes 246 with the formation of the hydrazone 1,4-adduct (Michael type) 250. The subsequent nucleophilic attack of the second amino group at the hydrazone carbon with the loss of a hydrazine carboxylate residue results in 2-phosphorylated quinoxalines 251a-i. This strategy affords a very efficient entry to quinoxaline phosphine oxides 251a, c, e-h and phosphonates 251b,... 

Reaction type 3 (equation 10), where the complete hetero-l,3-diene skeleton is incorporated into the newly formed ring system, occurs with compounds having both a nucleophilic center and an electrophilic center If these two functionalities are in positions 1 and 2, various types of six-membered ring systems become accessible 4,4-Bis(trifluoromethyl)-I,3-diaza-1,3-butadienes require only room temperature to react with acetyl cyanide to yield l,4,5,6-tetrahydropynmidin-6-ones [96] Likewise, certain open-chain 1,3-diketones (acetylacetone and acetoacetates) and the heterodiene form six-membered nng systems [97] (equation 19)... 

Bis(trifluoromethyl)-substituted heterodienes are electron-deficient species They therefore react preferentially with electron-rich multiple bond systems to give [4+2] cycloadducts (Diels-Alder reaction with inverse electron demand) [238]... 

Terrier et al. have widely described Bfxs 4-nitro-substituted participating in a series of Diels-Alder processes. Bfx 4-nitro-substituted system could participate as diene, C = C - C = C system, or heterodiene, C = C - NO2 system, in an inverse electron demand reaction [62,63] or as dienophile, C = C or N = O systems, in a normal electron demand reaction [64-68]. Fxs have been reported as 1,3-dipole through the substructure C = - 0 reacting with... 

Azabutadiene systems are well-known efficient heterodienes in aza Diels-Alder additions. The presence or absence of substituents especially in the 3-position seems to play an important role in the reactivity of 2-azadienes. For example, compounds 615 with PTAD provide the corresponding products 616 usually in high yields (Equation 92) C1994T12375, 2003H(61)493>. 

Readily available copper(II) complexes derived from o-nitrosophenols react with dimethyl acetylenedicarbonxylate to give the 1,4-benzoxazine products that would be expected from formal [4 + 2] cycloaddition across the diheterodiene system (Scheme 168).239 No such reaction is observed in blank experiments with uncomplexed tautomeric nitrosophenols hence the copper may cause sufficient electronic perturbation within the heterodiene complex to allow reaction to occur. 

Aiming at the pyranose form of sugars, normal type hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems (5-10) (see routes A - D in the general Scheme 1) which are also important targets in the "Chiron approach" to natural product syntheses (2.) Hetero-Diels-Alder reactions with inverse electron demand such as a, p-unsaturated carbonyl compounds (l-oxa-1,3-dienes) as heterodienes and enol ethers as hetero-dienophiles, are an attractive route for the synthesis of 3,4-dihydro-2H-pyrans (11). 

The spirocyclic phosphazenes (138) resulting from the reaction with 2-azidoalcohols dimerize <82TL853>. In the adducts of phenols with a heterodiene function in the 2-position <77ZN(B)84l> the phosphorus atom also becomes the center of a tricyclic system (139) (Scheme 45). 

Lactone 5 can be obtained in both enantiomeric forms or as a racemate according to the described procedure. The reaction sequence includes the in situ formation of an alkylidene-1,3-dicarbonyl system 7 which can act as a heterodiene in an intramolecular hetero-Diels-Alder addition. A small amount of the ene product 4 with de > 98% is formed at room temperature as well. The remarkable selectivity in formation of diastereomer 3 is explained by an energetically more favorable exo transition state 8 with a pseudo-chair arrangement having the methyl group quasi-equatorial. Polycyclic cis-fused compounds can also be synthesized by the procedure above,9 and a related sequence to the cannabinoid skeleton has been described using appropriate 1,3-dicarbonyl reactants.10... 

Benzo[3]thiete is a source of o-thioquinone methides, heterodienes which react with 1,4-naphthoquinones or 1,4-epoxynaphthalenes to give the benzo[ ]thioxanthene system. With the former reagents, the initial products undergo an autooxidation and 6,ll-dihydro-12//-benzo[7]thioxanthen-6,ll-diones result. The 6,11-epoxy adducts which are formed from the epoxynaphthalenes can be dehydrated to 12//-benzo[7]thioxanthenes or converted into the dihydrobenzothioxanthene-6-ol (Scheme 131) <1995JPR379>. 

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