Cycloaddition competing with

Because the fluorine substituents both inductively and hyperconjugatively withdraw electron density from the C(2)-C(3) tt bond, the LUMO is located there, and Diels-Alder reactions take place exclusively with this bond [25] 1,1 -Difluoro allene and fluoroallene reaet readily with a large selection of cyclic and acyclic dienes, and acyclic dienes, [2+2] cycloadditions compete with the Diels-Alder processes As shown in the example in equation 79, a significantly different regiochemistry is observed for the [2+4] cycloaddition compared with the [2+2]... 

Cycloaddition competes with [ 4 + 2] cycloaddition on irradiation of phenanthroquinone (427) with alkenes to give the corresponding ketooxetans (428) and dihydrodioxins (429), as well as products arising by... 

The photochemistry of carboxylic acid derivatives has been summarized by Coyle [20]. For arene carboxylic acid esters it has been shown that [2+2] cycloaddition competes with hydrogen abstraction by the excited ester from an allylic position of the alkene. The addition of methyl benzoate 17 to... 

In the case of benzophenone, the cycloaddition competes with the isomerization of 103 to cycloheptatriene. Exclusive isomerization was observed with acetophenone and acetone. Carbonyl compounds with triplet energies lower than 69kcal/mol prefer the cycloaddition path. Cyclopent-2-en-l-one is an exception to this rule in spite of its triplet energy of 74 kcal/mol, 2 + 2 cycloadducts were formed rather efficiently. 

Thermal intramolecular [2 - - 2] cycloadditions of 3-allylcyclopropenes, e.g. 127, are not only known but are also remarkably efficient (equations 46 and 53). Tricyclic products, e.g. 129, are formed and the cycloaddition competes with stereospecific Cope... 

The pressure dependence of the orbital symmetry-allowed [6 - - 4] cycloaddition of tropone with 1,3-dienes was first studied by le Noble and Ojosipe , who reported extremely small absolute values of and AV. A reinvestigation by Takeshita and his coworkers showed, however, that the activation and reaction volumes of these cycloadditions are of the same order of magnitude as those of Diels-Alder reactions (Scheme l7 entry 1). Dogan confirmed this finding with a study of the reaction between 1,3-butadiene and tropone in which a [6 + 4] cycloaddition competes with a [4 + 2] Diels-Alder reaction. The activation volume of the overall reaction was again found to be highly negative. However, the ratio between the [6+4] and [4+2] cycloadduct turned out to be almost pressure-independent, which means that the ifference between the activation volumes (SAT ) is almost zero and hence the activation volumes of both reactions are of the same value. 

In the case of unsubstituted oxepin, the [2 - - 4] cycloaddition competes with [4 -I- 6] process giving, for example a phthalazine derivative (13) besides (7) in the ratio (7) (13) = 2 1.2,7-Dimethyloxepin probably cannot undergo the [4 -I- 6] cycloaddition reaction owing to steric hindrances in its first step, i.e. the formation of an intermediate like (14) (Scheme 4). 

Coyle has summarized the photochemistry of carboxylic acid derivatives. For arene carboxylic acid esters it has been shown that [2-1-2]-cycloaddition competes with hydrogen abstraction by the excited ester from an allylic position of the alkene. The addition of methyl benzoate 17 to 2-methyl-2-butene gave a 1 1 mixture of the Paterno-Bilchi adduct 18 and the coupling product 19. Less electron-rich alkenes (e.g., cyclopentene) did add preferentially toward the benzene ring of 17 in an ortho- and metacycloaddition manner. Furans could also be added photochemically to methyl benzoate and other aren-ecarboxylic acid esters. The resulting bicyclic oxetanes could be transformed into a series of synthetically valuable products. [2-1-2]-Cycloadducts and/or their cleavage or rearrangement products have also been described for photoreactions of alkenes with diethyl oxalate,benzoic acid, " and carbamates. ... 

Again, it is noteworthy that 4-substituted 5-hydrdxythiazoles (24) react like 5-hydroxy-THISs with alkynes to give pyrroles and sometimes with alkenes to give exo-cycloadducts (Scheme 22). In the latter case other processes compete with the cycloaddition, becoming dominant when 24 is treated with azo-compounds, enamines, or heterocumulenes (31). 

Diene moieties, reactive in [2 + 4] additions, can be formed from benzazetines by ring opening to azaxylylenes (Section 5.09.4.2.3). 3,4-Bis(trifluoromethyl)-l,2-dithietene is in equilibrium with hexafluorobutane-2,3-dithione, which adds alkenes to form 2,3-bis-(trifluoromethyl)-l,4-dithiins (Scheme 17 Section 5.15.2.4.6). Systems with more than two conjugated double bonds can react by [6ir + 2ir] processes, which in azepines can compete with the [47t + 27t] reaction (Scheme 18 Section 5.16.3.8.1). Oxepins prefer to react as 47t components, through their oxanorcaradiene isomer, in which the 47r-system is nearly planar (Section 5.17.2.2.5). Thiepins behave similarly (Section 5.17.2.4.4). Nonaromatic heteronins also react in orbital symmetry-controlled [4 + 2] and [8 + 2] cycloadditions (Scheme 19 Section 5.20.3.2.2). 

In contrast LP-DE gives disappointing results for intramolecular imino Diels-Alder reactions, even in the presence of CSA. This is due to the fact that weak acids become strong acids in highly polar media such as 5.0m LP-DE and the protonation of diene, with concomitant diene isomerization, competes with cycloaddition [42]. This observation was supported by using trifluoroacetic acid (TEA). The imine 33 (Scheme 6.21) in LP-DE at room temperature in the presence of TEA gave a 1 1 mixture of cycloadduct 34 and the isomerized diene 35 within the unreacted imine 33. No Diels-Alder cycloadduct 36 was detected. 

Diels-Alder reactions also take place on the Si(100)-2 x 1 [62] and Ge(100)-2 x 1 [63,64] surface. The experiments by Hammers and his colleagues [65] indicate that the [4-1-2] cycloaddition reactions of 1,3-cyclohexadiene and 1,3-dimethylbutadiene on the Si(OOl) surface compete with the [2-1-2] cycloaddition reactions. 

The intermolecular dimerization of nitrile oxides has been described as a procedure to prepare Fx with identical substituent both in the 3 and 4 position (Fig. 3). This procedure is a [3 -F 2] cycloaddition where one molecule of nitrile oxide acts as 1,3-dipole and the other as dipolarophile [24-26]. Yu et al. has studied this procedure in terms of theoretical calculus [27,28]. Rearrangement of isocyanates competes with the bimolecular dimerization, with the former becoming dominant at elevated temperatures. 

The low yields, which are observed among styrenyl adducts, reflect a combination of the poor reactivity of the styrene at the low temperature of the reaction. For example, the combination of t-butyl Grignard with the 2,4-bis-OBoc-benzyl alcohol 15 affords the corresponding benzopyran 50 in only 50% yield even when carried out in the presence of 5-10 equivalents of the styrene (method H, Fig. 4.27).27 Yields for substituted benzopyran styrene adducts are still lower (method G, Fig. 4.27). For example, addition of methyl lithium to 2,4-bis-OBoc-benzylaldehyde 5 followed by the addition of the dienophile and magnesium bromide affords benzopyran 51 in a paltry 27% yield. Method F is entirely ineffective in these cases, because the methyl Grignard reagent competes with the enol ether and with styrene 1,4-addition of methyl supercedes cycloaddition. 

The same reaction sequence performed in methanol affords a mixture of diastereo-mers of the phosphorylated phosphinic ester 48b, of which one pure isomer can be isolated32 . In the presence of piperidine, reductive elimination of nitrogen 28,29) from 45 to give bis(diphenylphosphoryI)methane competes with the prevailing formation of the phosphinic piperidide 48c32). Expected trapping of 47 by [2 + 2]-cycloaddition with benzaldehyde fails to occur in place of 1,2k5-oxaphosphetanes, products are obtained which arise mainly by way of the benzoyl radical32,33). 

Simple criss-cross cycloadditions described so far are in fact limited to aromatic aldazines and cyclic or fluorinated ketazines. Other examples are rather rare, including the products of intramolecular criss-cross cycloaddition. The criss-cross cycloadditions of hexafluoroacetone azine are probably the best studied reaction of this type. It has been observed that with azomethine imides 291 derived from hexafluoroacetone azine 290 and C(5)-C(7) cycloalkenes < 1975J(P 1)1902, 1979T389>, a rearrangement to 177-3-pyrazolines 292 competes with the criss-cross adduct 293 formation (Scheme 39). 

A-Methylphthalimide (288) undergoes photoaddition in acetonitrile to ds-but-2-ene (289) to give d.s-l,6,7-trimethyl-3,4-benzo-6,7-dihydroazepine-2,5-dione (290).238 Evidence supports a concerted [ 2 + J2] pathway to the intermediate 291. Similar additions to other alkenes have been reported.239 Electron transfer quenching has been shown to compete with cycloaddition... 

The critical role of the ion-radical pair in the cycloaddition reactions in equation (75) is demonstrated by a careful measurement of the quantum yields as a function of the dienophile concentration and by a study of the effect of solvent and salt on the dynamics of the ion pair ANT+ , MA-. 212 However, in the reported cases, back electron transfer effectively competes with the coupling within the ion-radical pair and thus limits the quantum yields for the formation of the Diels-Alder adduct.212... 

Exocyclic double bonds at cyclic systems, which contain cross-conjugated double bonds, cannot be considered as a subgroup of radialenes and shall therefore be treated separately, although many of the structural features are comparable. However, in these systems the exocyclic and endocyclic double bonds are competing with each other as sites for Diels-Alder reactions, cycloadditions and electrophilic attacks. The double bond character of both, as measured by its distance, can provide some evidence for the selec-tivities. If no strain and conjugation are expected, the double bonds should be comparable... 

Another complication that can arise in these reactions is that a cycloaddition reaction of the radical intermediate formed in the tin hydride reduction, to an adjacent carbon-carbon double bond, can compete with the simple reduction reaction. This occurs when a five- or six-membered ring can be formed in an intramolecular cycloaddition reaction. For example, Beckwith and Lawrence96 found both five- and six-membered rings in the product when l-bromo-2,2,5-trimethylhex-l-ene was treated with tributyltin hydride (Scheme 15). 

For the enallene 352, it has been observed that the intramolecular [2 + 2] cycloaddition route competes with an also intramolecular ene reaction leading to cis-l-ethy-nyl-2-methylcyclopentane (354) via transition state 353 (Scheme 5.52) [149]. 

Some cases are known in which Diels-Alder reactions of electron-deficient allenes and dienes compete with [2 + 2]-cycloadditions (see also Section 7.3.7) [12, 151, 335, 336]. Recently, a phosphane-catalyzed [4 + 2]-annulation starting from allenic ester 337 and N-tosylaldimines 338 was published [337]. However, the formation of the tetrahydropyridines 339 isolated in excellent yields is explained by a multi-step mechanism and only resembles a Diels-Alder reaction. 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

In 2006, Akiyama and coworkers established an asymmetric Brpnsted acid-catalyzed aza-Diels-Alder reaction (Scheme 36) [59]. Chiral BINOL phosphate (R)-3o (5 mol%, R = 2,4,6- Pr3-CgH2) bearing 2,4,6-triisopropylphenyl groups mediated the cycloaddition of aldimines 94 derived from 2-amino-4-methylphenol with Danishefsky s diene 95 in the presence of 1.2 equivalents of acetic acid. Piperidinones 96 were obtained in good yields (72 to >99%) and enantioselectivi-ties (76-91% ee). While the addition of acetic acid (pK= 4.8) improved both the reactivity and the selectivity, the use of benzenesulfonic acid (pK= -6.5) as an additive increased the yield, but decreased the enantioselectivity. A strong achiral Brpnsted acid apparently competes with chiral phosphoric acid 3o for the activation of imine 94 and catalyzes a nonasymmetric hetero-Diels-Alder reaction. The role of acetic acid remains unclear. 

Dipolar cycloadditions of nitrile oxides 216 onto 1 gave much poorer yields of cycloadducts 217 than those of nitrones 205. The cycloadditions of 216 to 1 require higher temperatures and unfavorably compete with their dimerization to furoxanes. However, stable nitrile oxides 216 with bulky substituents R that hamper dimerization, can be used. The thermal rearrangements of 5-spirocyclopropane-annelated isoxazolines 217 always required higher temperatures than the isoxazolidine counterparts. Under these conditions the second cyclopropane ring was also cleaved to give furopyridines 218 (Scheme 48) [136, 137]. 

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