1,3-Dipolar reaction, high pressure

Compound 432, which can be easily prepared from trinitrochlorobenzene (76), treated with triethylamine in dipolar aprotic solvents provided good yield of the denitrocyclization product 433 (80JCS(P1)2205). Reaction of 2,3,5,6-tetra-chloronitrobenzene (434) with various 1,2-diamines under high pressure provided mixtures of the corresponding open products of the nitro group displacement, e.g. 435, and cyclized products, e.g. 436 (Scheme 69). Compound 436 was formed by denitrocyclization reaction, since compound 435 did not cyclize under the used conditions (94BCJ196, 95BCJ3227). 

Bistrifluoromethyl-l,3,4-thiadiazole 71 undergoes a Diels-Alder reaction with norbornadiene under high pressure to give the unstable cycloadduct 72 which rapidly loses dinitrogen forming the 1,3-dipolar intermediate 73. The [4+2] cycloaddition of the intermediate 73 with a second alkene affords product 74 in 29% yield (Scheme 5) <1997SL196>. 

Buckminsterfullerene Cgo generally reacts as electron-deficient dienophile or dipolarophile in numerous Diels-Alder or 1,3-dipolar cycloadditions103. The rates of reaction are again enhanced by an increase of pressure so that the yields are usually better at high pressure than at atmospheric pressure (Scheme 12). 

Because the dipolar cycloaddition is a bimolecular process, there exists the opportunity to accelerate the reaction under high pressure (232,233). The reaction... 

Weinreb and co-workers (16) reported a high-pressure-induced 1,3-dipolar cycloaddition of alkyl and phenyl azides with electron-deficient alkenes at ambient temperature. As a representative example, phenyl azide underwent cycloaddition with methyl crotonate (69) at 12 kbar to give the triazoline 70 (43%) and the p-amino diazoester 71 (53%). The high-pressure conditions resulted in high yield and a shorter reaction time (Scheme 9.16). 

Finally, Isaacs has investigated the effect of high pressure on the 1,3-dipolar cycloaddition of thiones to diazoalkanes, finding that the reaction is strongly accelerated by pressure which is extremely important in the case of sterically hindered substrates470. 

High pressure is generally effective in accelerating those reactions that involve either an ionization process or a dipolar transition state [9]. 

The first chapter, High Pressure Synthesis of Heterocycles Related to Bioactive Molecules by Kiyoshi Matsumoto, presents a unique high-pressure synthetic methodology in heterocyclic chemistry. Basic principles and fruitful examples for pericyclic reactions, such as Diels-Alder reactions, 1,3-dipolar reactions, and also for ionic reactions, such as Sn and addition reactions, are discussed. The review will be of considerable interest to heterocyclic chemists and synthetic chemists. 

Under high pressure, aromatic and heterocyclic nitriles can be trimerized to the 2,4,6-triaryl-1,3,5-triazines 141 176,177 the formation of dipolar intermediates as active species is assumed. The trimerization of benzonitrile in the presence of an alcohol under 2000-10000 atm at 100-120 °C involves the formation of benzimido esters as intermediates. In general, the formation of the trimer is favored with increasing pressure. On the other hand, long-chain or branched alcohols suppress the trimerization. Polar solvents increase the yield of trimer, and while acids can suppress the reaction, bases have little effect. 

Over the last 10 years, a burst of publications and reviews has been focused on the translation of different types of organic reactions towards the solid phase. The difficulty of transferring certain key reactions to the solid phase has stimulated solution phase library synthesis approaches which may be more effective. Cycloaddition reactions allow straightforward and often stereoselective construction of cyclic systems, which can serve as templates for further derivatization. Therefore, cycloaddition reactions play a key role in combinational chemistry sequences. The translation of cycloaddition reactions, especially 1,3-dipolar- [2] and Diels-Alder reactions [3] to the solid phase has been extensively studied. Although the benefits of high pressure for all type of cycloaddition reactions (e.g. [4 + 2] 1,3-dipolar, [2 + 2]) have been very well illustrated in past decades, the application of high pressure to solid phase cycloaddition reactions is still in its infancy. 

The action of 1,3,4-oxadiazoles on bicyclic alkenes under high pressure leads to multiply bridged products, e.g., 172 from norbornene 169 and 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole. It is suggested that the reaction involves a Diels-Alder addition to give 170, followed by loss of nitrogen to give 171 and, finally, a 1,3-dipolar cycloaddition (Scheme 10) <97SL196>. 

High-pressure organic synthesis (including hetero Diels-Alder and 1,3-dipolar [3 + 2] cycloaddition reactions and epoxide ring opening) 05Y770. 

The inseparable isomeric nitrones formed by reaction of deoxynojirimycin (DNJ) derivative 63 with dimethyldioxirane, gave the 1,3-dipolar cycloadducts 64 and 65 on reaction with trichloroacetonitrile (Scheme 12). The P-l-C-substituted-DNJ derivative 66 was obtained from the reaction of a related nitrone with methyl 3-butenoate under high pressure (15 kbar), but overall the access to this... 

The use of diphenylmethylenecyclopropanes, as opposed to methylenecyclo-propanes, greatly enhances the Pd°-induced [3 + 2] cycloaddition with alkenes to produce five-membered rings. A one-carbon ring-contraction route to cyclopentanes involves a high-pressure version of the known 1,3-dipolar addition of azides to O-silylated enolates, which removes some of the previously observed steric limitations of the reaction, so that the adduct (47) fragments, as shown, to produce the ring-contracted product (48). The intramolecular nitrile oxide... 

On the other hand, triazolines prepared by the high-pressure dipolar cycloadditions of azides to norbornene derivatives were thermally more stable. For instance, cycloaddition reaction of azides to 2-azabicyclo[2.2.1]hept-5-en-3-one was accelerated by high pressure, leading to a mixture of regioisomeric triazolines in good yields [77]. Furthermore, triazolines formed by high-pressure cycloadditions (14 kbar) of azides to norbornene cyclobutene diesters could be handled without decomposition [78]. 

---