Oxetanes endo-selective formation

Scheme 7.16 Endo-selective formation of oxetanes in the PB reaction of dihydrofuran with benzaldehyde (the Criesbeck Model).

The stereoselective formation of bicydic oxetanes was also reported in the PB reactions of diketones (Scheme 7.22). Here, Mattay and Griesbeck reported the endo-selective formation of oxetanes in the PB reaction of 1,3-dioxol derivatives with some methyl pyruvates [40]. The PB reaction ofarylglyoxylates with furan was also found to produce stereoselectively the bicydic oxetanes (Scheme 7.23) [41]. Neckers and coworker demonstrated the highly efficient formation of oxetanes in the intramolecular PB reaction (Scheme 7.24) [42]. 

It should be noted that the stereoselectivity is also completely different from that associated with triplet 1,4-biradicals. Thus, a highly exo-selective formation ofbicyclic oxetanes was observed during PET-promoted PB reactions, whereas a highly endo-selective formation ofbicyclic oxetanes was reported for PB reactions that proceeded via triplet 1,4-biradicals (see Scheme 7.25). The competitive reaction pathway for electron-rich alkenes explained a notable solvent effect on the regioselectivity and stereoselectivity of the PB reaction of dihydrofuran (Scheme 7.15). Thus, an endo-selective formation of 3-alkoxyoxetane was observed when using benzene, whereas the exo-isomer of 2-alkoxyoxetane was detected as a product of the PB reaction in acetonitrile (Scheme 7.15). 

However, even endo-selective formation of oxetanes from aromatic aldehydes and 2,3-di-hydrofuran 32 34 can be rationalized using this kinetic model (see p 3135). Here the dominant endo-lA diradical 10 collapses rapidly after intersystem crossing to the kinetically preferred oxetane 11, only if the singlet diradical is relatively long-lived does the reaction take the thermodynamically controlled course (e.g., with furan to 9). 

The malic acid derivative 12 reacted with benzaldehyde to yield the oxetanes 13a,b with a diastereomeric excess of 80% (Scheme 4) [10]. It should also be mentioned that the regioselectivity and the exo/endo selectivity are complete. The favored formation of 13a is explained by the dominant conformation depicted in A, B. The syn approach of benzaldehyde excited in the 3n,7r state with respect to the alkoxy substituent (transition state A) is hindered by electrostatic repulsion between the substituent and the carbonyl group having a reversed polarity in the excited state. The addition of benzophenone to the furan derivative 14 was stereospecific [11]. In this case, however, the attack of the 3n,TT excited ketone occurred in a syn manner with respect to the hydroxy function to yield 15. The conformation indicated in the transition state C was supported by calculations. 

When unsymmetrical carbonyls (R Rj) are used for the photochemical cycloaddition with furans, the inherent stereoselectivity should be considered, i.e., exo-oxetanes vs. endo-oxetanes (Scheme 9). Shima initially investigated the photocycloaddition reaction in 1965 and an NMR study by Whipple and Evanega later provided evidence for the preference of the exo-selective cycloaddition. The exo-selective formation of the bicyclic oxetanes and their chemical transformations are now accepted as powerful tools for preparing the synthetically and biologically important materials. " ... 

The mechanistic rationalization of the highly exo-selective formation of oxetanes has been exempHfied by Griesbeck et al. The idea was originally used for rationalization of the endo-selectivity in the reaction with 2,three-dimensionalihydrofuran derivatives (Scheme 10). " Namely, the stereochemical outcome is proposed to come from the relative stabihty of the intermediary triplet 1,4 diradicals (T-1,4-DR), whose conformations are suitable for the spin-orbit coupling (SOC) induced intersystem crossing (ISC) process. The Conformational Memory Effects (Griesbeck Model) in the stereoselectivity can be appH-cable to the stereochemical outcome for the reaction with furan (Scheme 11). 

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