Cycloaddition adduct

Endo adducts are usually favored by iateractions between the double bonds of the diene and the carbonyl groups of the dienophile. As was mentioned ia the section on alkylation, the reaction of pyrrole compounds and maleic anhydride results ia a substitution at the 2-position of the pyrrole ring (34,44). Thiophene [110-02-1] forms a cycloaddition adduct with maleic anhydride but only under severe pressures and around 100°C (45). Addition of electron-withdrawiag substituents about the double bond of maleic anhydride increases rates of cycloaddition. Both a-(carbomethoxy)maleic anhydride [69327-00-0] and a-(phenylsulfonyl) maleic anhydride [120789-76-6] react with 1,3-dienes, styrenes, and vinyl ethers much faster than tetracyanoethylene [670-54-2] (46). 

Methyl vinyl sulfone forms 1,2-cycloaddition adducts with aldehydic enamines, both with and without 3 hydrogens (37). Simple alkylation was reported to take place when phenyl vinyl sulfone was allowed to react with cyclohexanone enamines (58,60), but it has recently been shown that phenyl vinyl sulfone also forms cyclobutane adducts (60a). 

Dienamine 56a has been reported to undergo a 1,4 cycloaddition with acrylonitrile to form bicycloaminonitrile 57 in a 74% yield (61). A recent report has indicated that both possible 1,4-cycloaddition adducts are obtained from the reaction of acrylonitrile with a 1 1 equilibrium mixture of the linear- and cross-conjugated isomers of dienamine 56b (61a). 

Cyanoallene, when treated with the morpholine enamine of cyclohexanone, undergoes a 1,3-cycloaddition reaction to form 72 (89). The reaction between cyanoallene and diendiamine 73a produces di-1,2-cycloaddition adduct 73 (i 9). The 4a-azonioanthracene ion (73b) readily undergoes a 1,4-cycloaddition reaction with nucleophilic dienophiles such as enamines (89a). The cycloaddition is stereoselective so that the a- and... 

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Disulfenes react with 2 moles of enamine to produce a double 1,2-cycloaddition adduct (164a). 

Allenedienes 106 were submitted to a [4+3] intramolecular cycloaddition in presence of a [AuCl(lPr)]/AgSbF catalytic system (Scheme 5.28) [28]. The cycloaddition adducts 107 and/or 108 were obtained in good yields at room temperature. In contrast, this cycloaddition reaction requires a much higher temperature (110°C) when PtCl is employed as the catalyst [29]. This fact shows that the use of [AuCl(IPr)]/AgSbF catalytic system is critical for the success of this cycloaddition. 

Cycloaddition of furans followed by a subsequent transformation is still adopted as a useful strategy to prepare fluorine-containing benzene derivatives and isoquinoline compounds <00SL550>. The cycloaddition adduct can also be converted to a trifluoromethyl substituted cyclohexanone compound via hydrogenation and hydrolysis. Examples of these transformations are illustrated below. 

Azomethine ylides derived from (55,6/ )-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one (53) and various aldehydes have been prepared by Williams and co-workers (87,88) (Scheme 12.19). In a recent communication they reported the application of the azomethine ylide 54 in the asymmetric total synthesis of spirotryprostatin B 56 (88). The azomethine ylide 54 is preferentially formed with ( )-geometry due to the buLkiness of the aldehyde substituent. The in situ formed azomethine ylide 54 reacted with ethyl oxindolylidene acetate to give the 1,3-dipolar cycloaddition adduct 55 in 82% yield as the sole isomer. This reaction, which sets four contiguous stereogenic centers, constmcts the entire prenylated tryprophyl moiety of spirotryprostatin B (56), in a single step. 

The direct cycloaddition adduct was oxidized, resulting in the hydroxylated isoxazoline product (316). Better selectivities were obtained in 1,3-dipolar cycloadditions of 204 with nitrile oxides (317,318). The 1,3-dipolar cycloadditions proceeded with concomitant loss of the boron group to give the isoxazoline products in up to 74% ee (318). The alkene 204 was also tested in reactions with nitrones. The reactions proceeded with poor yields, but high selectivities were observed in two cases (318). Gilbertson et al. (319) investigated the use of chiral ot,p-unsaturated hexacarbonyldiiron acyl complexes 205 as dipolarophiles in reactions with nitrones. Selectivities of up to >92% de were observed. The iron moiety was removed oxidatively after the cycloaddition and the thioester was hydrolyzed. 

A subsequent study using STM suggested that although the majority (80%) of the product formed by adsorption of 2,3-dimethyl-1,3-butadiene on Si(100)-2 x 1 was the [4 + 2] cycloaddition adduct, the remaining 20% formed a [2 + 2] C=C cycloaddition product [222]. However, theoretical analysis led Doren [241] to propose that the [2 + 2] C=C cycloadduct observed in that study is actually a [4 + 2] cycloadduct that bridges two adjacent dimers, i.e., an interdimer product. 

The imine moiety of l//-l,4-bcnzodiazepin-2-(3//)ones reacts regio- and stereospecifically with a range of functionalized ketenes to afford substituted, fused /3-lactam [2+2] cycloaddition adducts (Scheme 21) <2004EJ0535>. The use of [4-(3 )-2-oxo-4-phenyloxazolidin-3-yl]acetyl chloride, as a homochiral ketene precursor, afforded a single product, the structure of which was established by X-ray crystallography, while the (4,y,5fJ)-diphenyl analogue provided a 1.8 1 mixture of chromatographically separable diastereomers. 

Jain and co-workers prepared highly substituted 1,2-diazetidine derivatives by the photolysis of adenine, which undergoes a [2+2] cycloaddition <1999IJB234>. In aqueous and acidic media adenine undergoes deamination followed by a [2+2] cycloaddition reaction to yield 287, whereas in alkaline solution it afforded direct the [2+2] cycloaddition adduct 288 (Scheme 45) (Equation 35). 

Although obtained only in low yields upon troublesome chromatography of product mixtures that contained much polymeric material, the tricyclic benzofuran and benzothiophene lactones (61) were shown to be isolable products from attempted Diels-Alder reactions on the allene ester precursors shown in Equation (32) <85JCS(Pl)747>. Although it was noted in the case of the two thiophenes that the tricyclics appeared to be forming from a precursor (presumably a dihydro form) on the chromatographic column, it was not possible to convert the crude suspected cycloaddition adducts directly into the aromatics by dehydrogenation with DDQ. Complex mixtures were obtained instead. It is possible that the actual dienophiles in these Diels-Alder reactions are alkynes. In a related study, the bis-lactone (62) was also obtained (Equation (33)) <86H(24)88l>. 

N-Substituted 1,2-diazocine 34, containing a conjugated diene moiety, was reacted with dimethyl acetylenedicar-boxylate (DMAD) to give the cycloaddition adduct 35 in excellent yield. The latter was oxidized with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) to give the benzodiazocine 36 (Scheme 7) <2004TL3757>. 

N-Protected 7-azabicyclo[2.2.1]heptan-2-one 1090 was conveniently synthesized from the cycloaddition adduct 1089 obtained in 60% yield by heating of methyl 3-bromo-2-propynoate 1088 with A -BOC pyrrole (Scheme 212) <1996JOC7189>. 

Hydrolysis of the vinyl groups from the metal center affords olefins. Weiss, Schubert, and Schrock investigated the reaction of the alkylidyne complex W(CCMe3)Cl3(dme) with cyclohexyl isocyanate (208). Two isocyanate molecules are incorporated into the complex as shown in Eq. (212). The reaction was postulated to proceed via a cycloaddition adduct of isocyanate to the metal-carbon triple bond and cleavage of the four-mem-bered ring into metal imido and ketenyl species. Subsequent insertion of a second isocyanate into the metal-ketenyl bond would then give the observed product. 

An interesting rearrangement, which appears to be anion-accelerated, takes place in the enol thioether, anion-terminated vinylcyclopropanes of type 14. ° The rearrangement proceeds at — 78 C and is reasonably stereoselective with regard to the final cyclopentene products (syn selectivity 16 1). Regioisomers are encountered in the formation of the dihydrothiopyran cycloaddition adducts 13 in several instances. The mechanism of this rearrangement appears to involve the enol thioether anion in accord with the well-documented donor acceptor principles " and may be related to similar rearrangements observed with trimethylsilyl enol ether terminated vinylcyclopropanes under fluoride ion or Lewis acid catalysis." " ... 

Another example demonstrating the difference in reactivity is the ozonolysis reactions of acetylene and ethylene. Ozonolysis of ethylene is a classical 1,3-dipolar cycloaddition reaction with an activation energy of 5 kcal/mol [106], whereas a larger activation energy of 11 kcal/mol was measured for the reaction of ozone with acetylene [107]. The 1,3-dipolar cycloaddition adduct, 1,2,3-trioxolene, has not been definitively observed as an intermediate involved in the acetylene ozonolysis. Nevertheless, according to the combined microwave and ab-initio calculation studies, the formation of similar van der Waals complexes in the course of ozonolysis has been established for both acetylene and ethylene [108]. 

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