Oxetanes regioselective formation

Scheme 7.8 Regioselective formation of oxetanes derived from furans or vinyl ethers the nucleophilicity rule.

When the nucleophilicities of the two carbons in alkenes differ significantly, the regioselective formation of 1,4-biradicals results. In fact, the regioselective oxetane formation was reported for the PB reaction of both furans [22] and vinyl ethers [23] (Scheme 7.8). Thus, 2-alkoxyoxetanes are formed exclusively during the PB reaction of furan derivatives. In contrast, 3-alkoxyoxetanes were selectively prepared in the PB reaction of vinyl ethers. This dramatic change in regioselectivity can be explained by the difference in the HOMO coefficient. Thus, in a furan ring, the C-2 carbon is known to be more nucleophilic, whereas the (3-carbon is the nucleophilic site in vinyl ethers. 

Scheme 7.11 Regioselective formation of oxetanes via radical ion pairs.

Dimerization - As reported in Part II, Chapter I the control of photochemical reactions in the constrained environment of a hydrotalcite clay as the supporting medium has been examined. This particular study examined the irradiation (X > 280 nm) of a mixture of 4-benzoylbenzoic acid and 2-phenylethe-nylbenzoic acid in this environment. While the regioselective formation of oxetanes was observed, dimerization of the phenylethenylbenzoic acid also takes... 

Photo-catalysed p-hydroxyalkylation of pyrroles on irradiation in the presence of aldehydes or ketones may proceed via regioselective formation of non-isolable oxetanes. ... 

Abe, M., Shirodai, Y., and Nojima, M., Regioselective formation of 2-alkoxy oxetanes in the photoreaction of aromatic carbonyl compounds with P,P-dimethyl ketene silyl acetals notable solvent and silyl group effects,/. Chem. Soc., Perkin Trans. 1, 3253, 1998. 

FMO calculations using PM3-C1 were used to investigate the regioselectivities obtained by the photochemical reactions between 2-pyridone and pcnta-2,4-dienoate.46 The hard and soft acid-base principle has been successfully used to predict product formation in Patemo-Buchi reactions.47 The 2 + 2-photo-cycloaddition of homobenz-valene with methyl phenylglyoxylate, benzyl, benzophenone, and 1,4-benzoquinone produced the corresponding Patemo-Buchi products.48 The photo-cycloaddition of acrylonitrile to 5-substituted adamantan-2-ones produces anti- and svn-oxetanes in similar ratios irrespective of the nature of the 5-substituent49... 

The photochemical reaction of carbonyl compounds and alkenes, which is referred to as the Paterno-Buchi (PB) reaction, was developed in 1909 [13], and is currently one of the most widely used methods for oxetane synthesis (Scheme 7.4). As exemplified in the PB reaction of benzophenone with 2-methylpropene [14], a selective formation of the oxetane is possible even when the photochemical reaction involves highly unstable molecules that is, the excited state of carbonyls. Due to its synthetic importance and mechanistic interest, the PB reaction is the most extensively studied synthetic method for oxetanes. Thus, several extensive reviews describing the PB reaction have been published since 1968, and the reader is directed towards these for further information [15]. In this chapter, methods that allow for the control of the regioselective and stereoselective formation of synthetically important oxetanes will be described. 

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). 

Bach and coworkers observed both regioselective and stereoselective oxetane formation during the PB reaction of acyclic vinyl ethers (Scheme 7.26) [15n], The stereoselectivity observed for such photochemical reactions cannot be explained using the Griesbeck Model, even though triplet, 14-biradicals were proposed as intermediates. Thus, the stereoselectivity was proposed to be largely dependent on product stability. 

Scheme 7.26 Regioselective and stereoselective formation of oxetanes in the PB reactions of silyl enol ethers.

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]. 

Branched-erythrono-1,4-lactones are accessible from the oxetane 66 which was derived thermally from diethyl mesoxalate 64 and 2,2-di-isopropyl-1,3-dioxole 65 [58]. An impressive improvement in the regioselectivity of oxetane formation was discovered with 2,3-dihydrofuran 67 as... 

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). 

It has been thought for some time that the interactions of triplet ketones with olefins involve a competition between hydrogen abstraction from, energy transfer to, and cycloaddition to the double bond 126>. Cycloaddition has generally been considered to proceed via a diradical intermediate. At first, the only evidence for a diradical was that the regioselectivity of oxetane formation often — but not always — is such as would be expected from the relative stabilities of the possible diradical intermediates 126>. Moreover, n,n ketone triplets are known to act like alkoxy radicals, which add to olefins, albeit less efficiently than do most other... 

The regioselectivity in oxetane formation is probably determined primarily by the orientation of the CT complexes. Additions of a-fluoroketones, which have such low reduction potentials as to be particularly hot 132> and therefore potentially unselective acceptors, do proceed with negligible regioselectivity 126>. The actual product ratio is quite complex kinetically because of all the various competing reactions of four separate intermediates. 

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. 

Fluorine-containing aldehydes, ketones and acid fluorides undergo photoinitiated cycloaddition reactions with fluorinated alkenes to give oxetanes.90 91 The addition of hexafluoroacetone (11) to fluoroalkenes can also be performed in the presence of the Lewis acid, aluminum chloride fluoride.92-1 22-1 23 Unlike the photochemical cycloaddition of hexafluoroacetone with trifluoroethene, the Lewis acid catalyzed addition is regioselective.92 Fluorooxetanes (c. g., 14) have also been synthesized by the addition of formaldehyde to fluoroalkenes in hydrogen fluoride.94 Examples of the formation of fluorooxetanes by [2 + 2]-cycloaddition reactions arc-given in Table 8. 

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