Cyclization hetero

Scheme 1.48. Cationic domino cyclization/hetero-Diels-Alder procedure.

Chrysean (10), prepared by bubbling hydrogen sulfide through a sodium cyanide solution, was among the first described thiazoles (53-57). Other 5-aminothiazoles are also most easily prepared bv hetero-cyclization (see Chapter 11. Section II.5.A). 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

The hetero ring in 4-(l -hydroxyalkylidene)-5-oxazolones is cleaved by alcoholic HCl to form alkyl a-acylaminoacylacetates, which cyclize to oxazole-4-carboxylates [Eq. (25)]. This rearrangement occurs directly in alkali, and a carbon-14 tracer study has substantiated a mechanism involving ring opening followed by the alternative ring closure. ... 

Diaminopyrimidines fused to a number of heterocycles (35) were also cyclized with one-carbon inserting agents to the corresponding hetero-cyclo-l,2,4-triazolo[l,5-c]pyrimidines 36 (75M1111 81JHC43 97JIC27). 

Substitution of the hetero group (XR ) at C-1 by the amino group (intermediate 149) and cyclization of its tautomer (150) with the participation of the methylene group (formation of 2,4-isomer 147). 

The cyclization pathway proposed (81UK1252) involves nucleophilic substitution of the hetero group (XR) by the formamide amino group to form either enyne formamide 157 or imine 158. 

Tocopheryl)propionic acid (50) is one of the rare examples that the o-QM 3 is involved in a direct synthesis rather than as a nonintentionally used intermediate or byproduct. ZnCl2-catalyzed, inverse hetero-Diels-Alder reaction between ortho-qui-none methide 3 and an excess of <2-methyl-C,<9-bis-(trimethylsilyl)ketene acetal provided the acid in fair yields (Fig. 6.37).67 The o-QM 3 was prepared in situ by thermal degradation of 5a-bromo-a-tocopherol (46). The primary cyclization product, an ortho-ester derivative, was not isolated, but immediately hydrolyzed to methyl 3-(5-tocopheryl)-2-trimethylsilyl-propionate, subsequently desilylated, and finally hydrolyzed into 50. 

Scheme 3.80. Domino cyclization/1,5-hydrogen shift/hetero-Diels-Alder sequence.

The asymmetric synthesis of (4R,93, 9aR)-4-phenyl-l-trimethylsilyloxy-9-vinylperhydropyrido[2,T ][l,4]oxazine with a high level of stereoselectivity in the cyclization of (3R,5R)-5-phenyl-3-phenylsulfanyl-4-(6-trimethylsilanyl-hex-4-enyl)-2-trimethylsilyloxy-morpholine was rationalized via AMI calculations <1998T10309>. AMI calculations suggested that the formation of l,6-dioxo-l,3,4,6,7,8-hexahydropyrido[2,Tf][l,4]oxazine-9-carboxylates 230 from acroyl chlorides 228 and 1,4-oxazinone 229 is favored over the hetero-Diels-Alder condensation (Equation 45) <1996JOC5736>. 

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

Mesoxalates are highly reactive substrates because of their strongly polarized carbon-oxygen bond. They have been used in pericyclic processes (e.g. Diels-Alder reactions,8 ene reactions,9 [3+2]10 and [2+2]11 cycloadditions), in aldol12 and Wittig as well as Friedel-Crafts reactions.13 Further applications arise from the use of the corresponding imines in hetero Diels-Alder reactions14 and electrophilic cyclizations.15... 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

Cyclization reactions of pyrimidines were studied, for instance, the reactivity of tetrahydropyrido[4,3-fc]pyrimidines with DMAD leading to dihydropyrimidinylethylamines <05TL1975> and pyrimido[4,5-rf]pyrimidines obtained efficiently by hetero Diels-Alder cycloaddition of methyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-... 

This type of method has been used to prepare l,2,4-thiadiazolo[2,3- ]pyridine derivatives. The oxidative hetero-cyclization is exemplified by the formation of compound 86 from thioacetamide 85 using nitrosobenzene (Equation 24) <2004S2975>. 

Unlike nickel Catalysts, palladium complexes do not catalyze the homo-cyclization reaction to give CDT or COD. The difference seems to be due to a different degree of hydride shift and atomic volume. With palladium catalysts, the hydride shift is easier, and hence linear oligomers are formed. The characteristic reaction catalyzed by palladium is the cocyclization of two moles of butadiene with one-hetero atom double bonds such as C=N and C=0 bonds to give six-membered rings with two vinyl groups (19) ... 

Weinreb86 has reported the Alder-ene cyclization of enallenes under thermal conditions (Equation (85)). Varying the substitution pattern of alkene and allene groups had little effect on the yield of cyclized product. One exception was a,/ -unsaturated ester 130(Equation (86)) cycloisomerization under thermal conditions led to the formation of the Alder-ene product 131 and the unexpected hetero-Diels-Alder product 132 in a 3 1 ratio. 

In a clever application of the hetero-Cope rearrangement, Martin used a Pd-catalyzed coupling of W-arylhydroxamates 362 with vinyl acetate to set up the [3,3] sigmatropic rearrangement 363 to 364 and final cyclization 364 to 365 [432-435]. Applications of this novel indole ring... 

The presence of hetero-atoms within the system, remote from the alkene double bonds, does not have an adverse influence on the SET processes that occur. Thus irradiation of the diene 33 in benzene solution with 1,4-dicyanonaphthalene as the electron-transfer sensitizer affords the cyclobutane 34 in 78% yield. Various examples of the reaction were described giving cyclobutane derivatives in 54-69% yield. Benzene, or an arene solvent, is vital for the success of the reaction. When acetonitrile is used, allylation of the sensitizer (akin to the photo-NOCAS reaction) results in the formation of the three products 35-3718. (2 + 2)-Cyclization of this type described for 33 is also seen with the dialkenyl ether 38. When 38 is irradiated using X > 350 nm or X > 450 nm in acetonitrile... 

Similar intramolecular cycloadditions are encountered where an ether linkage has been incorporated into the met a or para linking groups 123. In these cyclizations the better yields were obtained from the para-attached systems. The yields obtained are again dependent on the chain length of the separator and are indicated below the appropriate structures (124)57. Other hetero-atom-substituted cyclophanes (125) can be obtained by irradiation of the divinyl compounds (126)58,59. The use of tin and germanium derivatives... 

Like the cyclization of the parent system, the photocyclization of hetero analogues of norbornadiene was reported many years ago. Recent interest in this area will serve to illustrate the potential of the conversions. Thus the irradiation of the oxanorbomadiene system 259 brings about conversion to the oxepine 260138. The formation of 260 presumably arises by quadricyclane 261 formation, followed by secondary photolytic ring-opening. Other research has shown that irradiation of the oxanorbomadiene 262 follows the same reaction mode and it undergoes (2 + 2)-cycloaddition to the quadricyclane derivative 263. Apparently, in this instance, cycloreversion affords the ylide 264 that can be trapped by suitable addends, giving the adducts illustrated in Scheme 3139. 

The cyclizahon of amino alcohols should be an attractive method for the synthesis of N-heterocyclic compounds, mainly because they can be obtained in a single step and without the generation of wasteful byproducts. Carbon-nitrogen bond formation catalyzed by Cp lr complexes has been extended to the synthesis of N-hetero-cyclic compounds by the cyclization of amino alcohols. 

A wide range of dinucleophiles are prone to undergo cyclization processes by addition on both Co,=Cp and Cp=Cy bonds of an allenylidene moiety (1,2,3-hetero-cyclizations). The structure of the products generated depends mainly on the number... 

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