High pressure cycloaddition 1.3- dipolar

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]. 

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>. 

Improvements in 1,3-dipolar cycloaddition were achieved at high pressures (15kbar) (74), and by solvent-free microwave activation (739). 

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). 

Brillante and co-workers (33) conducted an intermolecular 1,3-dipolar cycloaddition of the aryl azide 162 with (trimethylsilyl)acetylene under high-pressure conditions (Scheme 9.33). The rate of cycloaddition increased logarithmically with pressure, and the yield of cycloadduct 163 was almost quantitative. 

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. 

Azetidines (215) have been synthesized by high-pressure-promoted [2 + 2] cycloadditions between imines such as 213 and / ,/i-disubstituted enamines such as 50116 in a weak polar solvent so that the dipolar intermediate 214 is neither stabilized nor intercepted (equation 46). The azetidines formed were unstable at a normal pressure and slowly decomposed into starting materials on standing. 

Buckminsterfullerene C6o generally reacts as electron-deficient dienophile or dipolarophile in numerous Diels-Alder or i,3-dipolar cycloadditions . 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 l2). 

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. 

In contrast to the complete regioselectivity observed in the 1,3-dipolar cycloaddition of nitronate 16b and methyl crotonate 42 or methyl cinnamate 44 shown in Scheme 9.14, the [3 -t 2] cycloaddition of yS-nitrostyrene (15a) and nitronate intermediate 16a was not completely regioselective. Regio-isomers 46 and 47 were formed in 83 % yield, as mixtures of diastereomers, in a 7 3 ratio after the high pressure-promoted domino cycloaddition of enol ether 14 with 2 equiv. fi-nitrostyrene (15a) (15 kbar, RT, 18 h, Scheme 9.15). The formation of regio-isomer 46 as major product was rather unexpected, since comparable 1,3-dipolar cycloadditions of nitrones and nitroalkenes [25] showed the opposite regio-isomer to be formed predominantly. This nitroso acetal (46) was converted to )S-lactam (48) via a base-catalyzed rearrangement (Scheme 9.16). This conversion appeared applicable to different hi- and tricyclic nitroso acetals and led to the formation of a novel class of bi- and tricyclic yS-lactams [26]. 

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 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... 

Stable tetrazoles 215 are formed by high-pressure 1,3-dipolar cycloaddition of azides and nitriles (Scheme 52) [80]. In this case, heating up to 140 °C could be combined with high pressure. 

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