Epoxynitrile cyclization

Stork, G. Cohen, J. F. Ring size in epoxynitrile cyclization. A general synthesis of functionally substituted cyclobutanes. Application to ( )-grandisol. /. Am. Chem. Soc. 1974, 96, 5270-5272. 

Lallemand, J. Y. Onanga, M. Ring size in (3-epoxynitrile cyclization. Tetrahedron Lett. 1975, 585-588. 

The synthesis of grandisol by Stork and Cohen illustrates the application of epoxynitrile cyclization, a facile general ring forming reaction developed at Columbia. ... 

Cyclobutanes are formed in preference to cyclopentanes during the epoxynitrile cyclization since the transition state for formation of a four-membered ring (i) seems to allow easy attainment of collinearity as opposed to the transition state for five-membered ring formation (ii). Geometric constraints imposed by the oxirane ring also explain the easier formation of cyclohexanes (iii) compared to cyclopentanes during this cyclization. 

Somewhat surprisingly, cyclobutanes are formed in preference to cyclopentanes from the cyclization of an epoxynitrile as shown below. 

Table 15. Functionalized Cyclobutanols by Intramolecular Nucleophilic Cyclization of (3-Epoxy Sulfones and (3-Epoxynitriles...

The reductive radical cyclization of 8- and e-epoxynitrile has been reported to be achieved using titanocene monochloride affording fused bi- and tricyclic (3-lactams (II and III, respectively, Fig. 23), [301]. 

Experimental evidence in support of this was provided by Stork, Cama, and Coulson (8) who studied the cyclization under basic conditions (KHH2> NHj-DME) of epoxynitriles 24 and 26. They observed that the formation of the cyclohexane ring 124- 25) was indeed easier than that of the cyclopentane ring (26- 27). 

Control of the size of the ring formed in this way is also applicable to the cyclization of yS-epoxynitriles. Thus the nitriles (35a and b) have been converted into either the cyclopropyl alcohols (36), or into the cyclobutanols (37) by application of either lithium di-isopropylamide or methylmagnesium bromide. 

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