Allylic oxetane formation

The above synthetic methods for oxetane all involve formation of a new C—O bond. Cyclization by formation of a new C—C bond has been applied with compounds having benzylic or alkylic CH groups. Recent examples of this type of ring closure are the rearrangement of trans- 2,3-epoxycyclohexyl allyl ether by means of s-butyllithium and the dehydrochlorination of a-cyanobenzyl 2-chloroethyl ether with aqueous base and phase transfer catalyst (equation 86). Both reactions probably involve carbanion intermediates (76TL2115, 75MIP51300). 

DFT studies on the facial selectivities of six Johnson-Claisen rearrangements (Scheme 5) analogous to those used in the synthesis of gelsemine have reproduced experimental results in five out of the six cases, but have predicted formation of the same product (21) in all six reactions. The selectivity in these cases has been attributed to a combination of steric repulsions between vinylic proton H(l) and allylic proton H(7) or H(14), and electrostatic attractions between C(l) and the oxetane hydrogens C(5)-H and C(16)-H. Both of these factors, however, apparently predicted the non-observed product in the conversion of (22) into (23)22... 

Scheme 7.9 Regioselective formation of oxetanes derived from silyl enol ethers and allylic silanes.

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 reaction of oxetane with carbenes follows two major pathways carbonhydrogen insertion or the formation of an oxygen ylide by reaction of the carbene and the oxetane oxygen. The oxygen ylide can produce a tetrahydrofuran by a Wittig rearrangement or generate an allyl ether by an intermolecular -elimination process (Scheme 61). 

Abel and Rowley (4) have done extensive work on the interaction of HFA and silanes with allylic substituents. At 100°C the reaction occurs according to Eq. (13). Decreasing the temperature leads to the formation of oxetane 13. 

Three modes of reaction of aldehydes with allylsilane bearing sterically demanding silyl substituents are mediated by the proper choice of Lewis acid (Eq. 39) [66a]. Thus, influenced by SnC, allyl-t-butyldimethylsilane reacts with aldehyde in 2 1 stoichiometry to afford a ketone derivative. In contrast, use of BF3 OEt2 leads to the formation of a 1,3-dioxane derivative, which is a 1 2 adduct. Furthermore, ZrCU-pro-moted [2 -r 2] cycloaddition of allylsilane and aldehyde fnmishes oxetanes in good yields [66b]. 

A similar rearrangement and geometric isomerization occur in the case of 2,4-hexadienemonooxirane. Irradiation of the spirooxirane 135 leads to cumulene, 135a, allyl alcohol 135b, and oxetane derivatives 135c. ° Cumulene formation is interpreted as occurring via a cyclopropylcarbene. 

The [2-1-2] cycloaddition of allylsilanes is applicable to the synthesis of substituted oxetanes from aldehydes and ketoesters [482, 498]. With aldehydes a ZrCU-mediated system using toluene as solvent is effective in the formation of oxetanes, whereas ketoesters are efficiently converted into oxetanes in a TiCh-mediated system (Scheme 10.183). N-Acylaldimines also undergo a similar [2-1-2] cycloaddition to afford azetidines [414]. The reactivity of N-acylaldimines to allyl-triisopropylsilane is completely different from that of N-tosylaldirniries, which are transformed into [3+2] cycloadducts by the ISI j- OEt2-promoted reaction [484]. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

Formation of Allyl and Aryl Primary AUyUc and HomoallyUc Alcohols from Vinyl Epoxides and Oxetanes. Vinylic epoxides can be coupled with aryl (eq 30) or vinyl (eq 31) iodides or tri-flates to form allylic alcohols in 40-90% yield. When employing palladium acetate as the catalyst, a reducing agent such as sodium formate is required in addition to the salts normally present under phase transfer conditions. 

In the presence electron-rich alkenes such as 2,3-dimethylbut-2-ene, irradiation of CA gives the allylethers 59 and 60, whereas with BQ, a substantial amount of the spiro-oxetane is also formed.The product distribution of the allyl ethers is rationalized by steric effects on the H+ abstraction and on the recombination of radicals as well as spin densities. The crucial role of solvent polarity in CA photochemistry is well illustrated by the results of a study into the reaction between the quinone and cyclohexanone enol trimethylsilyl ether 61 using time-resolved (ps) spectroscopy. The influence of the solvent occurs following the formation of the radical ion pair (CA - 61+-). The CA- species is short lived in nonpolar solvents and cyclohex-2-en-l-one and 62 are the reaction products, whereas in acetonitrile, the lifetime is much longer, which allows diffuse separation of the radical ion pair and transference of the TMS to the solvent. The resulting ketyl radical couples to CA - yielding 63. 

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