Cycloadditions with alkenes

SCHEME 12.20 [2+2] Cycloadditions with ketene silyl acetals. 

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A newer method for the preparation of nitronic esters, namely utilizing the (9-trimethyl-silyl ester, has been reported and these are prepared by the reaction of alkylnitro compounds and (V,(V-bis(trimethylsilyl)acetamide. These nitronic esters also undergo cycloaddition with alkenes to produce isoxazolidines (equation 54) (74MIP41601, 74DOK109, 78ACS(B)ll8). 

Benzene rings can undergo photochemical cycloaddition with alkenes. The major product is usually the 1,3 addition product, 116 (in which a three-membered ring has also been formed), though some of the 1,2 product (117)... 

The highly strained nature of methylene- and alkylidenecyclopropanes has been evidenced by spectroscopic measurements and X-ray analysis. The presence of the exocyclic double bond imposes a lengthening of the C(2)-C(3) bond as a result of an increase of the C(2)-C(l)-C(3) angle (compared to cyclopropane). This structural feature is reflected in a typical reactivity of these compounds which is a thermal or transition metal catalysed [3 + 2] cycloaddition with alkenes. This chemistry, usually referred to as TMM chemistry , has been the object of many studies and thoroughly reviewed by Binger and Buch [2] and Trost [8]. 

Very recently, [2 + 2] cycloadditions with alkenes activated by electron-with drawing groups have teen performed on the double bond of methylenecyc-lopropanes exo-substituted with two electron-donating groups, e.g., dimethyleneketene acetals 546 (Scheme 75, Table 44) [145]. 

Similar to the cycloaddition of allyl cations30, allenyl cations have been found to undergo cycloadditions with alkenes to afford bicyclic compounds31. The allenyl cations were generated from propargyl chlorides by treatment with Lewis acids. This reaction sequence proceeds via the cyclization 34 -------> 3532, in spite of the fact that... 

Cycloadditions tetrahydrothiophenes.1 The reaction of 1 with CsF in CH,CN generates a 1,3-dipole (a), which undergoes [3 + 2]cycloadditions with alkenes to give tetrahydrothiophenes in 65-85% yield. 

Cyclobutanones (11, 560-561). Ketenimium salts are more reactive than ke-tenes in [2 + 2] cycloadditions with alkenes to prepare cyclobutanones. The salts are readily available by in situ reaction of tertiary amides with triflic anhydride and a base, generally 2,4,6-collidine. The cycloaddition proceeds satisfactorily with alkyl-substituted alkenes and alkynes, but not with enol ethers or enamines.1... 

Af-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4+2] cycloaddition with alkenes and alkynes.15 The reaction has been utilized as a useftil method for the construction of heterocycles and acyclic amino alcohols. The reaction can be explained in terms of an inverse electron demand Diels-Alder type process that involves an electron-deficient hetero-diene with an electron-rich dienophile. Af-Acyliminium ions generated by the cation pool method were also found to undergo [4+2] cycloaddition reaction to give adduct 7 as shown in Scheme 7.16 The reaction with an aliphatic olefin seems to proceed by a concerted mechanism, whereas the reaction with styrene derivatives seems to proceed by a stepwise mechanism. In the latter case, significant amounts of polymeric products were obtained as byproducts. The formation of polymeric byproducts can be suppressed by micromixing. 

Table 4 Rate constants for cycloadditions with alkene radical cations a ...

Nitrones also undergo 1,3-dipolar cycloadditions with alkenes to furnish the corresponding isoxazolidines in a diastereo- and enantioselective manner when the... 

A -Protonated 2-azabuta-l,3-diene undergoes 4+- -2-cycloaddition with alkenes activated by electron-donating and electron-withdrawing substituents.The 2+ - - 4-cycloadditions of l,3-dithian-2-ylium ions with buta-1,3-dienes follow second-order kinetics which do not exclude a mechanism involving a concerted pathway. The... 

Oximes undergo similar cycloaddition with alkenes. This reaction provides more flexibility because oximes are easily available and are stable compounds. The reaction is, however, slower than cycloaddition of nitrones and generally requires high temperatures... 

Aside from the relatively trivial conversions of nitronates to the corresponding oxime and carbonyl compounds (10,11), the chemistry of nitronates remained relatively unexplored for much of the early 1900s. However, in 1964, Tartakovskii et al. (12) demonstrated that alkyl nitronate esters were competent partners in the newly discovered class of dipolar cycloadditions with alkenes (Scheme 2.1). Both cyclic and acyclic nitronates participated, thus providing a new functional group were the nitrogen atom existed at the center of an acetal (13). These compounds were subsequently referred to as nitroso acetals (14) or nitrosals (15). 

Several years later, Ioffe et al. (16) demonstrated that silyl nitronates also could be engaged in the dipolar cycloaddition with alkenes. These silylated isoxazolidine cycloadducts were then converted to the corresponding isoxazolines by treatment with sodium methoxide (Scheme 2.2). 

Among the most commonly applied chiral moiety for nitrones (2) is the N-a-methylbenzyl substituent (Scheme 12.6) (18-25). The nitrones 8 with this substituent are available from 1 -phenethylamine, and the substituent has the advantage that it can be removed from the resulting isoxazolidine products 9 by hydrogeno-lysis. This type of 1,3-dipole has been applied in numerous 1,3-dipolar cycloadditions with alkenes such as styrenes (21,23), allyl alcohol (24), vinyl acetate (20), crotonates (22,25), and in a recent report with ketene acetals (26) for the synthesis of natural products. Reviewing these reactions shows that the a-methylbenzyl group... 

Azomethine ylides such as 64 can be generated from tertiary amine A-oxides (63) by reaction with lithium diisopropylamide (EDA) (Scheme 12.22) (97). Several different chiral A -substituted azomethine ylides were prepared in this manner. The best results were obtained when using 64 in 1,3-dipolar cycloaddition with alkenes, but the de values obtained of the product 65 were <60%. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

Nitrones can be activated mainly in two different ways for the 1,3-dipolar cycloaddition with alkenes. In the reaction between a nitrone and an electron-dehcient alkene, such as an a,p-unsaturated carbonyl compound (a normal electron-demand reaction), it is primarily controlled by the interaction between HOMOnitrone-LUMOaikene (Scheme 12.64). By coordination of a Lewis acid (LA) catalyst to the a,p-unsaturated carbonyl compound, the LUMOaikene energy decreases and a better interaction with the nitrone can take place (16,17). 

Carbenes are only rarely detected, let alone isolated and characterized. Kinetically favorable exothermic reactions (among them cycloaddition with alkenes and insertion into CH bonds) generally preclude this. l,3-Diadamantylimidazol-2-ylidene, 8Ad, is an exception, in that it forms a stable solid, the crystal structure of which has been determined. ... 

Strained n/d/ -Bredt alkenes as well as -cycloalkenes will undergo [2 + 2] cycloadditions with alkenes. The bridgehead bicyclo[3.3.1]nonenones 16, produced as a transient species by the dehydrobromination of the corresponding bridgehead bromoketone, undergo cycloaddition with 1,1-dimethoxyethenc (15) to give the tricyclic ketones 17 in quantitative yields.7... 

Trifluoral was also converted to a C-(trifluoromethyl)nitrone [163] which underwent regio- and stereo-selective cycloaddition with alkenes, affording potentially useful aminoalcohols after N-0 bond cleavage (Eq. 52)... 

Phenoxysulfonyl azide. This novel azidosulfate is prepared in two steps from phenol (equation 1), preferably under homogeneous conditions. Sulfonyl azides arc reduced lo sullamaics, Ar0S03NH2, which undergo cycloaddition with alkenes to formn/.iridiiies.- ... 

Photogenerated nitrenes can undergo cycloaddition with alkenes intermolecular reaction leads to aziridine products (5.38), and intramolecular reaction in vinyl azides gives azirines (5.39). The bicyclic azirine from phenyl azide has not been isolated, but it is the intermediate that best accounts for the formation of a substituted azepine when this azide is irradiated in the presence of a secondary amine (5.401. 

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