Double cyclization relative reactivity

When this stereoelectronic requirement is combined with a calculation of the steric and angle strain imposed on the transition state, as determined by MM-type calculations, preferences for the exo versus endo modes of cyclization are predicted to be as summarized in Table 12.3. The observed results show the expected qualitative trend. The observed preferences for ring formation are 5 > 6, 6 > 7, and 8 > 7, in agreement with the calculated preferences. The relationship only holds for terminal double bonds. An additional alkyl substituent at either end of the double bond reduces the relative reactivity as a result of a steric effect. 

The relative reactivities of the two double bonds in / -di-isopropenylbenzene in THF have also been assessed.The cross-linking rate constant of pendant double bonds is - 3 orders of magnitude lower than the propagation constant for the first double bond, and the rate of cyclization is also extremely low. 

The observed results agree with the calculated trend. Relative rates of cyclization are in the order 5-exo > 6-endo 6-exo > 1-endo. The relationship holds only for terminal double bonds. An additional alkyl substituent at either end of the double bond reduces the relative reactivity by a steric effect. The underlying conformational and stereoelectronic effects can be modified by both steric and electronic effects of substituents. For example, a 5-methoxycarbonyl substituent promotes the 6-endo mode of cylization by an electronic effect. The reactivity of the (3-carbon is enhanced by the substituent. 

Pyrrolo[l,2- ][l,2]oxazines are a class of compounds with very few references regarding synthesis and reactivity. An interesting preparation has been described by intramolecular cyclization of IV-hydroxy pyrrolidines carrying a methoxyallene substituent at C-2 (242, Scheme 32). These compounds were obtained by addition of a lithiated allene to chiral cyclic nitrones 241. Cyclization occurred spontaneously after some days at relatively high dilution (0.05 M). Compounds 243 (obtained with excellent diastereoselectivity) can be submitted to further elaboration of the double bond or to hydrogenolysis of the N-O bond to form chiral pyrrolidine derivatives (Section 11.11.6.1) <2003EJ01153>. 

As mentioned above, the reactivity of alkoxyallenes is governed by the influence of the ether function, which leads to the expected attack of electrophiles at the central carbon C-2 of the cumulene. However, the alkoxy group also activates the terminal double bond by its hyperconjugative electron-withdrawing effect and makes C-3 accessible for reactions with nucleophiles (Scheme 8.3). This feature is of particular importance for cyclizations leading to a variety of heterocyclic products. The relatively high CH-acidity at C-l of alkoxyallenes allows smooth lithiation and subsequent reaction with a variety of electrophiles. In certain cases, deprotonation at C-3 can also be achieved. 

The tendency toward cyclization decreases considerably (lower kjkp value) for unsym-metric 1,6-dienes, such as allyl methacrylate, where the two double bonds have significantly different reactivities. The polymer contains linear repeat units, rings, and pendant double bonds in relative amounts determined by kc/kp. The pendant double bonds eventually react to yield a crosslinked structure. Reactants with more than two double bonds per molecule,... 

The cyclization in ether is effected by using Li Mg does not react. The high reactivity of the CH2Br group adjacent to a double bond towards Li is also observed in the formation of the four-membered ring 88. The structure of 86 is determined by nmr and mass spectra. In the nmr spectrum, 5 peaks (-20.5 Hz 4.0 Hz 6.0Hz 10.0 Hz and 451 Hz) are observed with the relative intensities... 

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