Substrates oxetanes

Initially, it was thought more likely that the electron poor metal atom would be involved in the electrophilic attack at the alkene and also the metal-carbon bond would bring the alkene closer to the chiral metal-ligand environment. This mechanism is analogous to alkene metathesis in which a metallacyclobutane is formed. Later work, though, has shown that for osmium the actual mechanism is the 3+2 addition. Molecular modelling lends support to the 3+2 mechanism, but also kinetic isotope effects support this (KIEs for 13C in substrate at high conversion). Oxetane formation should lead to a different KIE for the two alkene carbon atoms involved. Both experimentally and theoretically an equal KIE was found for both carbon atoms and thus it was concluded that an effectively symmetric addition, such as the 3+2 addition, is the actual mechanism [22] for osmium. 

The Evans method gives spiro-oxetane 30 when 2-propenylcyclohexanol (29) is employed as the substrate. 

However, attempts by Kiefer and Carlson59 to prohibit undesired bi-molecular reactions by irradiating 2,3,3-trimethyl-l-penten-4-one adsorbed onto silica gel were unsuccessful (due probably to steric inhibition of adsorption) the product composition was the same as that previously obtained in solution. Werbin and Strom80 attempted to restrain the freedom of movement of the radicals formed from the photolysis of vitamin K3 (2-methyl-1,4-naphthoquinone) by adsorption onto silica gel, but obtained the same mixture of dimers as that obtained from the irradiation in acetone solution, viz., syn and anticyclobutanes, an oxetane dimer, and a binaphthoquinone dimer. Photolysis of the solid substrate, however, produced only the syn isomer of cyclobutane, in this case no migration of radicals is possible, hence only one product. 

The overall course of reaction depends on the relative rate constants for the various secondary radical processes. Aliphatic ketones are often photoreduced to secondary alcohols (4.121, but although there are interesting features in the stereochemistry of the reduction, the method is not a worthwhile alternative to thermal reduction using hydride reagents, except in cases where the substrate is sensitive to basic conditions. Photoaddition of methanol is promoted in the presence of titaniurnfiv) chloride, both for acyclic and cyclic (4.33) ketones the titanium involvement probably starts in the early steps of the reaction, but the detailed mechanism is not known. Addition may also be a major pathway when cyclohexene is used as hydrogen source (4.341 unlike many other simple alkenes, cydohexene does not readily give oxetanes by photocycloaddition (see p. 126). 

Interesting results are obtained when 2-acetylthiophene is the substrate (74JOC2242). When irradiated in the presence of alkenes, the major products seem to be obtained by a [4 + 2] cycloaddition route the minor products are [2 + 2] adducts and oxetanes (Scheme 84). It has been suggested that the lowest - -> it triplet excited state may be an intermediate in these cycloadditions. In contrast to this, irradiation of 2-benzoylthiophene in the presence of 2,3-dimethyl-2-butene gave only the oxetane (298) in 76% yield no ring-addition products were found. An excited singlet state may be involved in this reaction. 

Ring-opening silylformylation has been observed by Murai and coworkers in reactions of cyclic ethers. When the cobalt complex Co2(CO)8 is used as the catalyst in reactions of epoxides, an excess of substrate is required to prevent further reaction of the product siloxy aldehyde.1192 Further investigation led to the discovery of [RhCl(CO)2]2/l-methyl-pyrazole as an effective catalyst combination for the reaction of oxi-ranes119b and oxetanes.J19c For example, oxetane undergoes silylformylation to give 4-(dimethylphenylsiloxy)butanal in 81% yield [Eq. (45)]. 

One example of oxetane formation proceeding by an intramolecular syn addition of a sulfenate ester intermediate has been reported (equation 5).16 This mode of cyclofunctionalization appears to fail unless the substrate enforces the correct alignment of the sulfenate ester.16b However, related 7-oxanorbomen-2-ols give oxetane products with an exo phenylsulfenyl group.17... 

The reaction of 3-phenyloxetane (10) with nitric acid in dichloromethane and trichloromethane under anhydrous conditions has been investigated.35 Quantitative conversion into 2-(nitrophenyl)propane-l,3-diol dinitrates occurs. The substrate reacts through its majority hydrogen-bonded complexed form initially by a mixture of aromatic nitration and oxetane ring opening. The nitration, perhaps surprisingly, proceeds at a rate comparable to that of / -dichlorobenzene. 

Methylene oxetanes have been used as substrates for the synthesis of l,5-dioxaspiro[3.2]hexanes. Epoxidation of the methylene group was achieved using dimethyldioxirane (DMDO), often in quantitative yield (Equation 25) <1998JOC6098>. 

Therefore, from epoxide 83 (Scheme 5.38), a 1,2-phenyl shift in intermediate MM would provide oxonium derivative NN, which would furnish, after rearrangement of the oxetane intermediate OO, the desired ketone 84. It is interesting to note that on the same substrates cationic gold derivatives (activated with silver salts) did not lead to the same final compounds, showing the unique reactivity of silver salts. 

Isatine derivatives gave the corresponding cycloadducts with high stereoselectivity when irradiated in the presence of furan and benzofuran [72]. The reaction of furan with acyl cyanides yields the corresponding oxetanes, but both diastereoisomeric endo- and exo-oxetanes are formed (Scheme 3.36). When chiral acyl cyanides are used, low asymmetric induction is observed [73]. Furan also reacts with chiral ketones. In this case, an ot-cleavage reaction before the 2+2 cycloaddition modifies the expected products (Scheme 3.37). When (—)-menthone was used as a substrate, a chiral product was obtained as a 2 1 diastereoisomeric mixture the most abundant product has the (1/ , 3R) configuration [74]. When the reaction was performed on carbohydrate 36, a complex reaction mixture was obtained (Scheme 3.38) [74, 75]. 

Pyrrole, like thiophene, does not react with benzophenone to give the corresponding oxetane. However, pyrrole reacts with aliphatic aldehydes and ketones to the corresponding 3-pyrryl carbinols. The alcohols derive from the cleavage of the corresponding oxetanes (Scheme 3.48) [94]. The yields increase when A -methylpyrrole is used as substrate, while the reactivity is depressed in the presence of substituents on the pyrrole ring. 

Since the introduction of the titanocene chloride dimer 67a to radical chemistry, much attention has been paid to render these reactions catalytic. This field was reviewed especially thoroughly for epoxides as substrates [123, 124, 142-145] so only catalyzed reactions using non-epoxide precursors and a few very recent examples of titanium-catalyzed epoxide-based cyclization reactions, which illustrate the principle, will be discussed here. A very useful feature of these reactions is that their rate constants were determined very recently [146], The reductive catalytic radical generation using 67a is not limited to epoxides. Oxetanes can also act as suitable precursors as demonstrated by pinacol couplings and reductive dimerizations [147]. Moreover, 5 mol% of 67a can serve as a catalyst for the 1,4-reduction of a, p-un saturated carbonyl compounds to ketones using zinc in the presence of triethylamine hydrochloride to regenerate the catalyst [148]. 

Recently, the photocycloaddition of L-ascorbic acid derivatives 73 with 4-chlorobenzaldehyde and benzylmethyl ketone was described which led to preferential attack on the less hindered a-face of the enone to give the oxetanes 74 and 75 (Sch. 20), respectively, with approximately 2 1 regioselectivity (33% de both) [65]. When the substrate is changed to... 

The nonstereospecific (using Zimmerman s definition) [108] nature of this reaction has been demonstrate by the use of stereoisomeric substrates which lead to oxetanes 114 in identical diastereomeric ratios. Another possibility for obtaining stereoisomerically pure oxetanes is the use of alkenes which simultaneously serve as quenchers for the carbonyl triplets, e.g., dienes. The photocycloaddition of acetone and 2-methyl-2,4-hexadiene (115) represents such a process leading to two regioisomeric oxetanes 116 and 117 where the substrate configuration is retained in 117 [75]. 

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). 

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