Regioselectivity of cycloadditions

The 3-oxo-2-pyrazolidinium ylides 315, easily available by reaction of the corresponding pyrazolidin-3-one with aromatic aldehydes, function as 1,3-dipoles in cycloaddition reactions with suitable alkenes and alkynes to provide the corresponding products. When unsymmetrical alkynes are used, mixtures of both possible products 316 and 317 are usually obtained (Equation 45). The regioselectivity of cycloadditions of the reaction with methyl propiolate is influenced by the substituents on the aryl residue using several 2,6-di- and 2,4,6-trisubstituted phenyl derivatives only compound 316 is formed <2001HCA146>. Analogous reactions of 3-thioxo-l,2-pyrazolidinium ylides have also been described <1994H(38)2171>. 

Fluoride ion catalyzed 1,3-dipolar cycloaddition of bromo nitrile oxide, obtained in situ from dibromoformaldehyde oxime 184, to nonactivated alkynes provides a new approach to the synthesis of neuroactive isoxazoles. However, the regioselectivity of cycloaddition in this case is not high—products 185 and 186 are obtained in a 1 1 to 1 1.4 ratio (equation 80). Cycloaddition reaction of hydroximoyl chlorides and acetylene was snc-cessfully carried out also in the presence of NaHCOs as a base. For instance, a-keto oximes 187 were reacted with acetylene and NaHCOs to give isoxazoles 188 in good yields (equation 81). 

The regioselectivity of cycloaddition of -t with conjugated dienes is the opposite of that observed in numerous nonphoto-chemical reactions of these dienes and provides further evidence for the importance of frontier orbital interactions in determining exciplex geometry and product stereochemistry. 

One more example of high stereo- and regioselectivity of cycloaddition has been provided by the reaction of enantioenriched azido ketone 551 that bears a tethered nitrile group which undergoes cyclization to the bicyclic tetrazole 552 (Equation 107) <2005JA1313>. 

A list of classical dipolarophiles has been tested successfully and from the whole of the results it is concluded that the regioselectivity of cycloadditions involving non-symmetrical dipolarophiles is temperature dependent and that all cycloadditions are highly stereoselective and favor formation of the isomer resulting from an exo transition state. 

The regioselectivity of cycloaddition of singlet 2-methylenecyclopenta-l,3-diyl (23), generated by photoelimination of nitrogen from 7-methylene-2,3-diazabicyclo[2.2.1]hept-2-ene (24), to alkenes has been explained in terms of... 

Cycloaddition with enone reactants has been studied using cyclopentenone or cyclohexenone derivatives in order to avoid side reactions resulting from cis-trans isomerization of the alkene. In the case of cyclopentenone or cyclohexenone, regioselectivity of cycloaddition is influenced by the substituents at the C-3 position as well as whether or not the 4-position is a heteratom. 

C.ii. Regioselectivity of Cycloaddition Reactions. It is apparent from several of the preceding examples that with certain substituent patterns on the diene and/or alkene, more than one regioisomerie cyclo-adduet is possible. When the 2-substituted diene 55 reaets with alkene 56, two orientations for the X group are possible relative to R the meta orientation in 57 and the para orientation in 58. Dienes with substituents at Cl,... 

It has been claimed that the regioselectivity of cycloaddition of N-methylazomethine ylide to C70 is slightly affected by using microwave irradiation as the source. By choosing an appropriate solvent (o-dichlorobenzene, ODCB) and emitted microwave power, the ratio l lb is modified from 50 50 to 45 55 [48, 94] (Eq. (97), Table 4.31). 

The two layers of donor-acceptor interactions in this reaction play distinctly different roles - the formation of new o-bonds in the cycle and the observed regioselectivity of cycloaddition are controlled by the aikene" diene interactions whoteas the stereoselectivity is controlled by the interaction. The... 

Danishefsky and coworkers have used the racemic P-phenylsulfinyl-a,P-unsaturated ketone (160) as an a,P-ethynyl carbonyl synthetic equivalent and found that the phenylsulflnyl group did not compete with the carbonyl group in determining the regioselectivity of cycloaddition with the l-methoxy-3-trimethylsilyloxy-1,3-butadiene (161), now known as Danishefsky s diene [140] (Scheme 5.54). Loss of methanol and phenyl sulfenic acid from the initial cycloadduct (162) gave the aromatic product (163). 

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