Diastereoselectivity oxetane formation

A highly diastereoselective oxetane formation was identified in the PB reaction of dihydropyridone with a m-hydroxybenzaldehyde derivative (Scheme 7.33). The chiral auxiliary, when bound to the aldehyde, offered a binding site to which the reaction partner could attach by two hydrogen bonds. In the hydrogen-bonded complex that was produced, the two enantiotopic faces of the alkene could be differentiated [52]... 

Figure 7.34. A simplifled kinetic scheme for the diastereoselective oxetane formation in the Paterno-Bdchi reaction (Aj and 2 as A, and include intersystem crossing steps) (by permission from Buschmann et al., 1989).

Figure 7.35. Preferred conformations for intersystem crossing during the diastereoselective oxetane formation (adapted from Griesbeck and StadtmQller, 1991).

Figure 6.9. Temperature dependence of the diastereoselectivity of oxetane formation (22 , 23 A, 24 ) by cycloaddition of menthyl phenylglyoxalate (19) to tetra-methylethylene (20) and ketene acetal (21) (by permission from Biischmann et al., 1991).

Adam, W., Stegmann, V. R. Unusual Temperature Dependence in the cis/trans-Oxetane Formation Discloses Competitive Syn versus Anti Attack for the Patemo-Buchi Reaction of Triplet-Excited Ketones with cis- and trans-Cyclooctenes. Conformational Control of Diastereoselectivity in the Cyclization and Cleavage of Preoxetane Diradicals. J. Am. Chem. Soc. 2002,124, 3600-3607. 

Adam and coworkers reported the regioselective and diastereoselective formation of oxetanes during the PB reaction of allylic alcohols (Scheme 7.27) [43, 44]. This group proposed that hydrogen-bond interactions in the exciplex played an important role in controlling the selectivity. D Auria and coworkers also observed a site-selective and diastereoselective formation of oxetanes in the PB reaction of 2-furylmethanol derivatives (Scheme 7.27) [45]. 

Scheme 7.27 Regioselective and diastereoselective formation of oxetanes in the PB reaction of allylic alcohols.

The simple diastereoselectivity of the photocycloaddition of electronically excited carbonyl compounds with electron rich olefins was studied as a function of the substituent size—at identical starting conditions ignoring the electronic state involved in the reaction mechanism [123], The [2+2] photocycloaddition of 2,3-dihydrofuran with different aldehydes in the nonpolar solvent benzene resulted in oxetanes 118 with high regioselectivity and suprising simple diastereoselectivites the addition to acetaldehyde resulted in 45 55 mixture of endo and exo diastereoisomer, with increasing the size of the ot-carbonyl substituent (Me, Et, i-Bu, t-Bu), the simple diastereoselectivity increased with preferential formation of the endo stereoisomer (Sch. 37). 

Bach and coworkers investigated the photocycloaddition of 7V-acyl, 7V-alkyl enamines 125 with benzaldehyde [125]. The 3-amido oxetanes 126 were formed with excellent regioselectivity (analogous to reactions with enolethers—vide supra) and good diastereoselectivity (Sch. 41). Enamines, not deactivated by acylation at the nitrogen atom are poor substrates for Paterno-Buchi reactions due to preferred electron transfer reactivity (formation of the corresponding enamine radical cation and subsequent reactions). 

Both oxetanes were formed with exclusively the exo-phenyl configuration. The regio- and diastereoselectivity observed are in accord with the assumption of a PET process involving the oxidation of the ascorbic acid derivatives and the formation of the carbonyl radical anions. In these special instances 1,4-biradical and 1,4-zwitterion stabilization result in similar product regiochemistry. The relative configuration of the products favors the assumption of a PET-process. 

The formation of oxetanes from the irradiation of benzaldehyde and furan is reported to occur with a diastereoselectivity of 212 1 for the exo-6 and endo-l isomers respectively (Griesbeck et al) and similar reaction of this aldehyde with the enamine 8 favours the oxetane 9 over 10 in what the authors describe as an unprecedented facial diastereoselectivity (Bach and Brummerhop). 

Further work has been carried out to study the facial diastereoselectivity of the addition of benzaldehyde to alkenes. ° In this study the three enamines (49)-(51) were used as the substrates to which benzaldehyde was added photochemically. The results show that addition does occur to all three enamines but with varying degrees of success as far as diastereoselectivity is concerned. Thus addition to (49) gives the two oxetanes (52) and (53) but with only 32% de. Poorer selectivity is observed with (50) when (54) and (55) are obtained. The best de of 62% is achieved from (51) where the products are (56) and (57). The photochemical addition of the aldehydoester (58) to the enamine (59) results in the formation of the oxetane (60). This product is obtained in around 30% yield and it can be transformed into racemic oxetin (61). Bach has reviewed the stereocontrol that can be exercised on the formation of oxetanes. The regioselectivity of the addition of triplet carbonyl compounds to alkenes has been interpreted for the first time in terms of hard and soft acid-base systems. The authors of this report suggest that there is overall good agreement between HSAB prediction and experimental fact. 

For a smooth transition from the previous section, we will continue by discussing the work of Sun and coworkers, who reported their efforts on the application of a new directing group in an organocatalyzed MCR in 2013 [25]. The rarely used oxetane proved to be the ideal hydrogen-bond acceptor that supports the formation of the desired transition state. The previously used ethers already exhibited some desired directing effects and delivered perfect diastereoselectivity (>95 5 dr), but proved ineffective for enantioselectivity (<5% ee). By employing the oxetane, however, the envisioned aza-Diels-Alder reaction proceeded as intended with excellent diastereo (>99 1 dr) and enantioselectivity (99% ee). The proposed transition state of this desymmetrization clarifies the selectivity of the reaction the chiral phosphoric acid allows the amine to approach only from the front face (Scheme 14.10). 

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