Endocyclic enol ether

Reacdons of 2-f2-nitrovinyl -l,4-ben2Qquinone with furans, indoles, and endocyclic enol ethers form angular, fused heterocyclic quinoidring systems fsee Eq. 8.13. "... 

PREPARATION OF ENDOCYCLIC ENOL ETHERS VIA ALKYNOL CYGLOISOMERIZATION... 

Entry Alkynyl alcohol Endocyclic enol ether Isolated yield Reference... 

Enol ethers and enol acetates of cyclic 1,3-dicarbonyl compounds also afford mixtures of regioisomers on irradiation in the presence of allene, the preferential orientation of addition for enol ethers being mainly head-to-tail.9-11 Endocyclic enol ethers on the other hand, e.g. 2.3-dihydro-4//-pyran-4-ones 4, add regioselectively to allene with exclusive formation of head-to-head adducts.11... 

Several cyclofunctionalization reactions of alkynic alcohols are synthetically useful. Metal ion-promoted cyclofunctionalization of ris-2-propargylcyclopentanol systems proceeds by the 5-exo mode (equation 77 and Table 23).197 Protiodemetallation or reductive demetallation provides the cyclic enol ether in high yields. This method has been used by Noyori in the synthesis of prostacyclin (PGh).197b,197c Reactions with catalytic amounts of mercury(II) or palladium(II) salts gave the endocyclic enol ether as the major product.197 -198 A related cyclization with Ag2C03 has been reported by Chuche.191 Schwartz... 

Cyclization of tran.s-isomcr (4) proceeds more slowly and results in an endocyclic enol ether 5. 

Subsequent hydroboration of endocyclic enol ether 5 proceeded stereoselectively to give alcohol 6, which was further oxidized with tetra- -propylammorrirrm perrutherrate (TRAP) and A-me% lmorpho-line 7V-oxide (NMO) (Ley et al. 1994) to afford ketone 7. Oxidative removal of the /r-methoxyberrzyl (PMB) group followed by treatment with ethanethiol and zinc triflate effected cyclization of the D-ring... 

Epoxidation of endocyclic enol ether 37 with dimethyl dioxirane (DMDO) followed by one-pot reduction with DIBALH produced a 10 1 mixtrrre of alcohols, in which the major isomer possessed... 

Glycals serve as activated sugars because of the inherent reactivity of the endocyclic enol ether. Consequently, they have been extremely useful substrates in their complementarity to native activated sugars. Additionally, they have been used to demonstrate versatility not directly available from other sugar derivatives. In a good example of the utility of allylsilanes and silylacetylenes in C-glycoside chemistry, Ichikawa et al. [91] demonstrated a preference for the a anomer in all cases. The results, shown in Scheme 7.17, included a demonstration that a characteristic nOe can be used to confirm the stereochemical outcome of the reaction with hw-trimethylsilylacetylene. 

Cl 1-25 of the milbemycins. The intramolecular spiroketalization theme was slightly altered to feature an endocyclic enol ether [86] by condensation of a lithio-2-benzenesulfonyl-tetrahydropyran with a suitable epoxide. An alternative but not enantiospecific approach from lactone B 3 comes from a double Baeyer-Villiger oxidation of bicyclo[2.2.1]heptane-2,5-dione to control [107] the relative stereochemistry in the B ring. The acetylenic partner was in turn derived from two different routes, the more selective being an anti hydroxyl group directed alkylation of a homopropargylic alcohol. 

An efficient strategy for the eonstruction of endocyclic enol ethers (35) based on the Suzuki-Miyaura eoupling of the enol phosphate (33) and the alkylborane (34) followed by the ring-closing metathesis (RCM), has been described by Fuwa and Sasaki (Scheme 8). This methodology has been successfully applied in the synthesis of a variety of spiroacetals, including the cytotoxic marine metabolites attenols A and B. 

Danishefsky has described the synthesis of 173 which represents the fully functionalized core of staurosporine, a potent protein kinase C inhibitor. Central to his strategy is incorporation and then unmasking of a double glycosyl donor by activation of (i) an endocyclic enol ether and (ii) an exocyclic enol ether, as outlined in Scheme 36. 

Synthesis of the C9-C28 spiroacetal fragment of didemnaketal B was achieved using a similar strategy. Suzuki-Miyaura coupling of an alkyl borate (derived from iodide 102 and B-methoxy-BBN) to the phosphate 103 afforded endocyclic enol ether 104. Spirocyclization took place after cleavage of the silyl ethers with subsequent treatment with mild acid (PFTS), affording the doubly anomerically stabilized spiroacetal 105 in high yield. 

Alternatively, an intramolecular oxymercuration/reduction sequence can be used to effect spirocyclization with endocyclic enol ethers [77]. This method was recently used by Tan and coworkers [78] in their synthesis of acortatarin A (Scheme 33). 

Classically, treatment of an endocyclic enol ether with an electrophilic halide reagent such as iV-bromo- or A[-iodosuccinimide [72,113-117], or organoselenium reagents (PhSeX) [118-122], affords electrophUe-substituted spiroacetals (Scheme 53). The halide is then removed using reductive methods or used for further elaboration of the spiroacetal toward the target molecule. 

Shair et al. [123] have used an electrophilic spirocychzation in their synthesis of cephalostatin 1 (Scheme 54). The spiroacetal of the western half, 228, was obtained by treatment of the endocyclic enol ether 226 with PhSeBr, giving the mono-anomeric spiroacetal 227 in excellent yield. Transformation to the desired doubly anomeric spiroacetal 228 was achieved by reductive removal of the bromide, followed by epimerization with CSA. 

McDonald EE, Connolly CB, Gleason MM, Towne TB, Treiber KD (1993) A new synthesis of 2,3-dihydrofurans cycloisomerizati[Pg.48]

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