Oxetanes stereoselective formation

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. 

Scheme 7.18 Stereoselective formation of oxetane in the PB reaction of O.S-ketene acetal.

In the PB reaction of furan derivatives with benzaldehyde (as shown in Scheme 7.13), a site-random - but highly stereoselective - formation of exo-oxetanes was reported (Scheme 7.13) [15q,30]. The highly exo-selective formation of oxetanes was explained by the conformational stability of the intermediary triplet biradicals. The anomeric effect was proposed to play an important role in stabilization of the exo-isomer precursor (Scheme 7.20). Thus, the inside conformer which should... 

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]. 

Scheme 7.22 Stereoselective formation of bicyclic oxetanes in the PB reaction of 1,3-dioxol derivatives.

Scheme 7.25 Regioselective and stereoselective formation of oxetanes via radical ion pairs.

Abe, M., Fujimoto, K., Nojima, M. Notable Sulfur Atom Effects on the Regio- and Stereoselective Formation of Oxetanes in Paterno-Biichi Photocycloaddition of Aromatic Aldehydes with Silyl 0,S-Ketene Acetals. J. Am. Chem. Soc. 2000, 122, 4005-4010. 

Examples of C(sp )-0 reductive elimination of olefin oxides from Pt center have been reported recently (Fig. 12) [33]. In the case of Pt oxetanes derived from strained cycloolefins, norbomene and cyclooctene, the elimination reactions can proceed readily at 40 60°C in a number of solvents and even in the solid state. The reaction is highly stereoselective formation of a single isomer of an olefin oxide is observed for norbomene. Importantly, as for complexes 9 and 14 (Fig. 8), the reactivity of the Pt oxetane 19 with an alkyl ligand trans- to the sulfonate is much higher than that of an isomeric compound 18 where the pyridine ligand, a poorer leaving group is trans- to the alkyl. 

The photocycloaddition of carbonyl compounds with 2-siloxyfurans 95 has been investigated in detail by Abe and co-workers. The stereoselective formations of exo-oxetanes 96 and 97 were observed in high yields. The regioselectivity was found to be largely dependent upon the nature of the carbonyl component,... 

Abe, M., Fujimoto, K., and Nojima, M., Notable sulfur atom effects on the regio- and stereoselective formation of oxetanes in Paterno-Biichi photocycloaddition of aromatic aldehydes with silyl O, S-... 

Resin-based chemistry has been used to construct 480 from 481 by use of boron trifluoride to mediate both the cyclization and cleavage steps <1999AGE1121 >. When the monosaccharide was bound to the polystyrene resin (Merrifield and MPP type) by an alkylsulfonyl linker 482 and cyclization was mediated by 2- r/-butylimino-2-diethylamino-l,3-dimethylperhydro-l,3,2-diazaphosphorine, the reaction had low stereoselectivity and the products included tricyclic oxetanes and oxiranes <2004EJ04177>. The Mitsunobu reaction was used to obtain intramolecular N-alkylation of 483 and formation of 484 <2005AGE3732>. 

In the PB reaction using O.S-ketene silyl ether, oxetane formation was highly stereoselective (Scheme 7.18) [36]. Such stereoselectivity could be explained by the preferred conformation of the intermediary triplet 1,4-biradical for the ISC process. 

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. 

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

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