High pressure technique 4+2 cycloaddition

Inferences drawn from literature data prompted us to apply the high-pressure technique to the [2+2]cycloaddition of isocyanates to glycals. The lack of reactivity at room temperature and atmospheric pressure, the exceptional sensitivity of cycloadducts to temperature, and the large negative activation volume of [2+2]cycloadditions,in contrast to the usually low sensitivity of intramolecular rearrangements to this parameter, strongly supported the use of high pressure for this reaction. 

Some other aspects of nitrile oxide chemistry that will grow in importance in the future involve the use of high pressure (> 10 kbar) to enforce hitherto slow or not feasible cycloadditions. Of particular relevance for nitrile oxides will be to find substantial improvements for practical, cost-efficient, large-scale reactions (351). Solid-phase techniques, adaptation for combinatorial chemistry, or improved versions for dehydrating nitroalkanes will all play an increasingly important role. 

Another application of this high pressure cyclization technique to ste-reochemically more complex aldehydes has recently been described (Scheme 4-VII).34b For example, aldehyde 15 reacts with ( )-l-methoxy-butadiene to give exclusively adduct 16, which can be epimerized to 17. A Felkin model for cycloaddition can again be used to rationalize these results (cf. 18). It is the greater rigidity and steric bulk of this system that imparts the high facial selectivity relative to the glyceraldehyde derivative in Scheme 4-VI. 

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