Chlorobenzene cycloaddition

As in the case of the solution-phase protocol, Diels-Alder reactions of the polymer-bound pyrazinones la,b were carried out in refluxing chlorobenzene (132 °C) and it required 1-2 days to drive these reactions to the completion (Scheme 44). Intramolecular cycloaddition of pyrazinone Ic was carried out in refluxing bromobenzene (bp 156 °C). Microwave-assisted cycloadditions of these substrates were performed in 1,2-dichlorobenzene at 220 °C and in significantly shorter reaction times (10-40 min). The product distribu-... 

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

A general hetero-Diels-Alder cycloaddition of fulvenes with azadienes to furnish tetrahydro-[l]pyrindines has been described by Hong and coworkers (Scheme 6.241 see also Scheme 6.92) [424]. A solution of the azadiene and fulvene (1.2 equivalents) precursors in chlorobenzene was heated under open-vessel microwave irradiation for 30 min at 125 °C to provide the target compounds in excellent yields and with exclusive regio- and diastereoselectivity. Performing the reactions under conventional conditions or under microwave irradiation in different solvents provided significantly reduced yields. 

Ring opening of the benzocyclobutenes or the extrusion of CO2 and SO2 requires high temperatures. Therefore, the cycloadditions are carried out in solvents such as toluene, chlorobenzene, o-dichlorobenzene or 1,2,4-trichlorobenzene at elevated temperatures. Some representative examples are shovm in Table 4.2. 

Kobayashi and co-workers (42) reported a general synthetic pathway for the incorporation of oligosaccharides into [60]fullerene via cycloadditions between glycosyl azides and the fullerene (Scheme 9.42). The cycloaddition of 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl azide 197 with [60]fullerene in refluxing chlorobenzene... 

A -Sulfonyl-2,2 -biindoles undergo a formal [4-I-2] cycloaddition with various dienophiles to produce indolocarba-zoles <2004TL4009>. Thus, reaction of 171 with A -benzylmaleimide in chlorobenzene in a sealed tube produces the cycloadduct in moderate yield (Equation 105) as the only observable product (Table 11). It is proposed that the reaction proceeds by an initial Michael addition, followed by a rapid cyclization and loss of the phenylsulfonyl group during the aromatization process. Similar cyclization reactions are observed with A -methylmaleimide, dimethylace-tylene dicarboxylate, and 1,4-naphthoquinone. 

Cycloadditions to mesomeric pyrimidine betaines (234 and 235) with DMAD in refluxing chlorobenzene gave high yields of the pyridones 237 and 238 via the intermediate cycloadducts 236, which were not... 

Pseudomonas putida mediated cis-dihydroxylation of bromo or chlorobenzene supplied the requisite chiral starting material 44 for a second synthesis of (+)-7-deoxynarciclasine reported by Hudlicky [18,19]. Subsequent to protection of the diol as the acetonide45 (Scheme 8), its cycloaddition reaction with the N-acylnitroso compound derived from benzyl-N-hydroxycarbamate 46 by in situ oxidation, occurred with complete regio and stereospecificity togive the bromo adduct 47. In a similar fashion, the chloro compound 48 was obtained. 

Breton and Martin <2002JOC6699, 20010L3185> reported the cycloaddition of 3-methyl-l,3,5-triazabicy-clo[3.2.0]hept-6-ene-2,4-dione 63 with a number of different dienes leading to the formation of [4+2] cycloaddition products. Most of the Diels-Alder cycloadditions of 63 were carried out in either benzene or chlorobenzene at a temperature of 100-150 °C. 

Similarly, treatment of C60 in refluxing dry chlorobenzene with dendrimer 57 possessing an azide focal point, prepared from the corresponding bromide (52) with sodium azide in DMSO, gave rise (69%) to a controlled, one-step cycloaddition affording the amine substituted fullerene 58, 1531... 

Cycloaddition reaction of 2,3-diphenylcyclopropenone with l,3-diphenyl-2//-cyclopenta[/]-phenanthren-2-one in chlorobenzene at 150°C for 80 hours under argon in a sealed tube produced 9,10,12,13-tetraphenyl-ll//-cyclohepta[/]phenanthren-ll-one in 29% yield. 

Surprisingly, dialkylamino oxazinones 35 and the 2-phenyl analogue 32 underwent cycloadditions with acetylene diester and ethyl propiolate, albeit under harsh conditions (reflux in xylene or chlorobenzene) (Scheme 50, refs. 23, 46). 

Intramolecular cycloaddition of 1,2,4,5-tetrazines to a nitrile group has also been reported. Heating 3-[(2-cyanophenyl)oxy(sulfanyl)]-l,2,4,5-tetrazines in chlorobenzene affords condensed 1,2,4-triazines 14.203... 

Dieh-Alder reactions with benzyne. Shepard has recently demonstrated that benzyne generated from chlorobenzene and LiTMP undergoes expected Diels-Alder cycloadditions with reactive dienes. The reaction with furane itself fails because of a base-promoted side reaction. 

Styrenes may give Diels-Alder adducts with arynes, the exo-cyclic double bond being part of the diene moiety Yields are generally rather low. The competition between [4+2] cycloaddition and Michael addition of benzyne (generated from chlorobenzene and... 

The Bose research group has developed a large variety of [2+2] cycloaddition reactions of ketenes with imines to form yS-lactams [16, 112, 113]. In 1991, Bose et al. described the synthesis of a-vinyl yS-lactams by [2-p2] cydoaddition of a,p-unsaturated acyl chlorides with a SchifF base in chlorobenzene. Reaction times were reduced from several hours with conventional methods to 5 min under the action of microwaves [112], and yields of the desired adducts were improved from very low to approximately 70% when compared with classical methods. 

In 1993, it was found that alkyl azides react with C o in a 1,3-dipolar cycloaddition manner [35]. The course of the reaction is closely analogous to the 1,3-di-polar addition of alkyl diazo compounds. Preliminary results on the reaction of Cso with organic azides were complicated. Treatment of Qo with SEM azide in refluxing chlorobenzene afforded two major products 3 and 4 (Fig. 2). While isN-i C spin-spin coupling experiments supported the structure for 4, the NMR spectrum of 3 contained a resonance at 160 ppm coupled to which was... 

In 1953, Robert s experiments on the conversion of C-labeled chlorobenzene with KNH2 into aniline gave strong support to the intermediacy of ortho-benzyne in this and related reactions. Additional direct evidence for the existence of ortho-benzyne was provided by the observation of its IR spectrum, sohd-state dipolar NMR spectrum, and NMR in a molecular container, and by UV photoelectron spectroscopy. Even at low temperatures, arynes are extraordinary reactive. The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. The pericyclic reactions can be divided into several categories such as Diels-Alder reactions, [2-f2] cycloadditions, 1,3- and l,4-dipolar cycloadditions, and the ene reactions. Arynes react with practically aU kinds of nucleophiles. More recently, the transition-metal catalyzed reactions of arynes have been studied, in particular those involving palladium. 

While preparing benzonorbornadienes by the Diels-Alder cycloaddition of substituted benzyne intermediates with furan. Caster and coworkers discovered significantly differentregiochemistries be tween bromobenzene 121 and chlorobenzene 124 in the n-BuIi induced metallation step (Schemes 12.40 and 12.41) [72]. In the case of bromobenzene 121, benzyne intermediate 122 was generated via bromine-Uthium exchange, followed by elimination of UF trapping by furan then afforded 6-fluoro-9-oxabenzonorbornadiene (123). In contrast, aryne 125 was produced... 

FIGURE 23 Cycloaddition of diphenylketene to butyl vinyl ether. Common logarithm of the relative rate constant versus Kirkwood s dielectric function. Data from Reichardt and Weldon (2011, p. 181). Solvents were 1, cyclohexane 2, chlorobenzene 3, acetone ... 

Lewis acids, such as EtAlCL, GaCb and AlBrs, catalyze the cycloaddition of allenes to alkenes to give methylenecyclobutanes 151. 1-Alkenes and sterically hindered olefins, such as 4,4-dimethyl-2-pentene, do not react, and from butadiene only polymeric products are obtained. Substituted olefins react more readily, i.e. 1,1,2,2-tetraalkylethylene > 1,1,2-trialkylethylene > 1,2-dialkylethylene. The acid catalyzed [2+2] cycloaddition reaction most likely proceeds via a vinyl cation. The slightly exothermic reaction proceeds at room temperature in chlorobenzene and EtAlCb was used as a catalyst in the examples listed in Table 6.7... 

Remarkably, this complete regiocontrol was due to the sterical hindrance imposed by the chlorine substituent on the diyne 88 building block—and therefore the use of alkynyl chloride 88 turned out to be ideal for the regioselective assembly of the chlorobenzene moiety of sporolide B (94). The [2 + 2 + 2] cycloaddition product 91 was then transformed into the o-quinone 92 to prepare the second key step of this total synthesis, the thermally induced intramolecular Diels-Alder macrocyclization reaction (Scheme 7.20). 

---