2-Substituted oxepanes

These reductions of lactols with Et3SiH 84b in combination of BE3 -OEt2, TfOH, or TMSOTf 20 have become standard reactions for synthesis of cyclic ethers [62-69]. Thus even co-hydroxyketones such as 1837 cyclize readily with excess EtsSiH 84b in the presence of TMSOTf 20, in high yields, via the lactols 1838, to give cyclic ethers such as the substituted oxepane 1839 in 90% yield [65] (Scheme 12.18). 

Summary of synthetic routes to benzo-, mono- and di-substituted Oxepanes 580... 

Table 7 Synthetic Routes to Benzo-, Mono- and Di-substituted Oxepanes...

A Pd-catalyzed Michael-type cyclization (Equation 21) is described as a method for construction of a substituted oxepan system <1999TL1747>. 

Stereoselective preparation and Cope rearrangement of 2-CF3-substituted r-2,3-bis(alkenyl)oxiranes opens a facile approach to diverse 2-trifluoromethyl-4,5-dihydrooxepines. Subsequent reduction or oxidation of the latter provide 2-CF3-substituted oxepanes or oxepines, respectively <2004CL438>. 

Boron trifluoride etherate promotes the fWt/a-selcctivc oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The oxacyclization transformations may mimic ringforming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products <2002JOC2515>. 

A transformation of dihydropyranones to substituted oxepanes is described <2001H(55)855, 2001TL1095>. The key steps are ring-enlargement followed by the action of a silyl enolate (Scheme 48). 

Several synthetic routes to oxepanes involving the formation of two C—C bonds from bifunctional components (equation 42) have been reported <72HC(26)1>. Thus oxepanes (156 X = CH2Br, Y = CH(C02Et)2) and (157 X = CH(C02Et)2, Y = CH2Br) have been synthesized by a double nucleophilic displacement of bromide ion using appropriately substituted... 

Oxepane (159) was obtained in high yield as an unexpected product of rearrangement from the peroxyacid oxidation of the substituted furan shown in equation (45) (81JOC2589). The isomerization of a bis-epoxide intermediate to the ring expansion product (159) occurs in the final step of the latter reaction. ... 

Intramolecular cycloaddition of fV-benzyl-substituted 3-O-allylhexose nitrones furnishes chiral oxepane derivatives. The regioselectivity of the cycloaddition depends on several factors such as (1) the structural nature of the nitrone, (2) substitution and stereochemistry at 3-C of the carbohydrate backbone, and (3) substitution at the terminus of the O-allyl moiety. A mixture of an oxepane and a pyran is formed in the intramolecular oxime olefin cycloaddition of a 3-O-allyl carbohydrate-derived oxime <2003T4623>. The highly stereoselective synthesis of oxepanes proceeds by intramolecular nitrone cycloaddition reactions on sugar-derived methallyl ethers <2003TA3899>. 

Pyran derivatives, mainly isochromans, undergo homologation to corresponding oxepane derivatives (Scheme 49) by a sequential reductive opening-lithiation-electrophilic substitution-cyclization <1995T3365, 2004S1115, 2006AHC135>. 

We have systematically examined the facility with which DTPP promotes the cyclodehydration of simple diols to cyclic ethers 1,3-propanediol (1) - oxetane (2) (2-5%) 1,4-butanediol (3) te-trahydrofuran (4) (85%) 1,5-pentanediol (5) - tetrahydropyran (6) (72%) 1,6-hexanediol (7) - oxepane (8) (55-68%). Increased alkyl substitution at the carbinol carbon s gnificantly diminishes the facility for cyclic ether formation. For example, a mixture of meso- and d, 1 —2, 6-heptanediol gave only 6-10% of the cis- and trans-2,6-dimethyltetrahydropyrans when treated with DTPP. While diol 1 resists cyclodehydration with DTPP to oxetane, some 2,2-di-substituted 1,3-propanediols are readily converted to the appropriate oxetanes [e.g., 2-ethyl-2-phenyl-l,3-propanediol -> 3-ethyl-3-phenyloxetane (78%)]. 

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