Ethers and Lactones

New alkaloids based on the aspidoalbidine skeleton include the 17-methoxy-Aa-formyl (CCXIXa)and 17-methoxy-Aa-acetyl (CCXIXb) derivatives (12), aspidofendlerine (CCXX 33) and 21-oxoaspidoalbine (CCXXIa 36). Kromantine (Volume VIII, p. 505) turns out to be the A-acetyl analog (CCXXIb) of aspidoalbine described in Volume VIII, p. 445 (84a). The structures of these alkaloids were readily deduced from NMR- and mass-spectral data as described in the previous volume and also by correlation with known compounds. For example, CCXX was methylated to aspidolimidine (XIV) and CCXXIa to 21-oxo-O-methyl- 

The structures of this group of bases were briefly reported in Volume VIII. The interest of their chemistry and establishment of their absolute configuration warrants a fuller account here. 

J = 9 and 5 cps) acetate groups. The molecules must therefore contain an aspidospermine framework and the partial structure CCXXVIII. The protons on C-20 can in fact be clearly recognized as an AB pattern (2.02 and 2.57 ppm, J = 18 cps in CCXXIIIb) in the NMR-spectra of the original alkaloids. 

The ethylidine side chain was located in the first two cases by hydrogenation to the 14,19-dihydroderivatives (CCLXI and CCLXII) in which a diagnostic peak appears at M — 41. This peak is insignificant when the side chain is located at position 20 (Volume VIII). Further evidence was adduced from the NMR-spectra in which the isolated C-3 proton is found as a singlet superimposed on the C-2 proton quartet (4.38 ppm) (12, 34, 38). Rotatory dispersion measurements have shown that CCLVIII and CCLIX have the absolute configuration illustrated (Section II,A) (34, 

The positive rotation of CCLX points to the same configuration for this alkaloid (23). 

The diastereoisomers of dihydropinol (127) (575, 541), which also have a cineole-like odor, as well as their probable precursors (-h)-dihydrocarveol and (— )-isodihydrocarveol [diastereoisomers (51)] 541, 542) are components of caraway oil. The diastereoisomeric linalool oxides (128) (furanoid) and (129) (pyranoid) have been found during the last few years in a large number of essential oils as important aroma-forming substances. In most cases these hydroxy ethers are accompanied by linalool (6) from which they may be formed in a suc- 

The dye-sensitized photooxygenation reaction has to be considered as a biomimetic process 451) involved in the formation of deoxylinalool oxide (132) 459), rose oxide (134) 456) and nerol oxide (135) 459) from linalool (6), citronellol (9) and nerol (8), respectively. 

Verbena oil contains, besides (134) and (135), the two furan derivatives (140) and (141) as trace components 280). 

Hop ether (136) and karahana ether (139) are monoterpenoid compounds which occur in Japanese hop (Shinshu-wase) 426), while the occurrence of (-h)-matatabi ether (138) and of its isomer (137) is limited to the essential oil of Actinidia polygama Franch. et Sav. (Ternstroemiaceae) 261, 716). 

Monoterpenoid furan derivatives occur in a limited number of flavor-yielding plant species. Menthofuran (140), as the oldest example 195), is present in all the oils obtained from Mentha piperita L. in which its pronounced odoriferous character contributes to the pleasant flavor 

---

Scheme 13 Cyclic ethers and lactones by allyloxylation-cyclization of unsaturated alcohols and carboxylic acids.

Intramolecular Addition Formation of Cyclic Enol Ethers and Lactones from Pent-4-yn-1-ols and But-3-yn-1-ols... 

Scheme 10.14 Mechanistic proposal for cyclic enol ether and lactone formation based on a common ruthenium vinylidene intermediate.

Hydroxy steroids give complex mixtures from which ll/ ,18-Iactones (5-13%) and 11,19-ethers and lactones (8-35%) can be isolated.72... 

An X-ray study of vertaline hydrobromide established the structure and absolute stereochemistry of vertaline as shown in 51 (32, 43). The relative stereochemistry at C-l and C-3 in all alkaloids in the group is the same as in the biphenyl alkaloids for example, the biphenyl ether and lactone group are linked to the quinolizidine ring in axial and equatorial configurations, respectively. 

The resulting lactam radicals formed add to the olefins by similar processes already discussed for amides, ethers and lactones. 

Application to the Synthesis of Cyclic Enol Ethers and Lactones... 

As a unique reaction, treatment of thionoesters (41) or thionolactones with Ph3SnH in the presence of Et3B at room temperature provides the reduction products (42) of thiocarbonyl groups to methylene groups (eq. 7.19) [44, 45]. Thus, this is the indirect reduction of esters to ethers, and lactones to cyclic ethers, since thionoesters and thionolactones are prepared from the corresponding esters or lactones with Lawesson s reagent. 

Cationic Polymerization. Cationic polymerization is initiated by the transfer of a cation from the catalyst to the monomer. It allows a wider choice of monomers with double bonds, including carbonyls, cyclic ethers, and lactones. The ion may be within a carbonium or an oxonium ion. Friedel-Crafts halides, like AlCls or A CoHsJCL, are strong Lewis acids and initiate the polymerization directly. Weak Lewis acids need a... 

Danishefsky. S., Kitahara, T., McKee, R and Schuda, P. F Reaction of silyl enol ethers and lactone enolatcs with di-methyl(meihylenc)ammonium iodide. The bis-a-methylenation of pre-veruolcpin and pre-vemomenin,7. Am. Chem. Soc.. 98,6715, 1976 see also J. Am. Chem. Soc.. 99, 6066, 1977. 

Alkenation of esters by this method yields enol ethers, and lactones give cyclic enol ethers. 

A further series of ketone catalysts containing spiro ethers and lactones have been examined in the asymmetric epoxidation of phenylcyclohexene (cf Table 5, entry 2 94% yield, 98% ee) (Figure 11). The substituents on the spiro ring appeared to effect enantioselectivity both sterically and electronically <2005T6409>. 

Several other 1,3,2-oxazaborolidines have been successfully used as chiral catalysts or reagents in borane-promoted reduction of ketones, imines and oxime ethers, and lactones as well as in aldol condensations, Diels-Aldercycloadditions, and ally Imetal additions to aldehydes. ... 

Stereospeeific synthesis of IJ-dieues. Corey el al. have described a new synthesis of 1,3-dienes based on the highly stereospeeific cis addition of alkylcopper reagents to a,p-acctylenic carbonyl compounds (3, 108). Thus the reaction of methyl 4-trimethyl-siloxy-2-nonynoate (I ) in THF with divinylcopperlithium (1.25 cq.) at - 90° and then at — 78° affords the pure madduct (2) in > 90% yield. Treatment of (2) with melhanolic hydrochloric acid effects cleavage of the trimethylsilyl ether and lactonization to give (3). 

Activated carbon, in keeping with the enhanced complexity of carbon-based chemistry, possesses an extensive array of surface moieties, including hydroxyl groups, carboxylic acid groups, aldehyde groups, keto groups, cyclic ethers, and lactone groups. 

Ring-opening polymerization of cyclic ethers and lactones has been a major area of research in Lewis acid-promoted reactions. In particular, aluminum compounds have been investigated in depth not only because of their high oxophilicity and ability to initiate polymerization but also because of their commercial availability and low cost. 

Fractionation of liquids or solids is possible if the constituents of the mixture exhibit large differences in vapor pressure, mass, and polarity. Low molecular weight hydrocarbons and lipophilic organic compounds, such as esters, ethers, and lactones, are easily extractable. 

Sila-l,3-dithiacyclopentane readily inserts strained ethers and lactones, as well as chlorofluoroketones, to give 1 2 polymers. With (CF3)2CO, however, the cylic monomer 13 has been reported, though slight changes in reaction conditions give only polymer. In contrast, the six-membered dithiasilacyclohexane 14 only yields the monomer (equation 55)13. 

Cleavage of esters, ethers, and lactones. The reagent resembles CsHaSLi (3, 188 5, 415) and CaHsSNa (4, 465) in reactivity for cleavage of hindered esters and methyl aryl ethers. In addition it cleaves lactones to methylthio carboxylic acids an example is the conversion of butyrolactone to CHGSCH2CH2CH2COOH in 69% yield. A direct comparison indicates that this reagent is superior to lithium thiophenoxide for cleavage of the lactone 1 to 2. 

Stepwise two-electron-transfer reduction of cyclic ethers and lactones with alkalide K, K (15-crown-5)2 07COC1126. 

In the examination of plant waxes various analytical methods have been used, including ultraviolet and infrared spectroscopy, and thin-layer, column, and gas-liquid chromatographies (Eglinton and Hamilton, 1967). The infrared spectrum has been used to indicate hydroxy compounds, ketones, ethers, and lactones, as well as the more common esters and hydrocarbons. In the use of thin-layer or column chromatography, infrared spectra can be used to make sure that there is no carryover of one class of components into another. 

Gimstone, F.D., and B.S. Perera, The Halogenation of Some Long-Chain Hydroxy Alkenes with Special Reference to the Possibility of Neighbouring Group Participation Leading to Cyclic Ethers and Lactones, Chem. Phys. Lipids 11 43-65 (1973). 

Among a host of other phosphine-catalysed reactions in which the initial step is the formation of a reactive phosphoniobetaine intermediate by addition to a carbon-carbon double or triple bond are intramolecular cyclisations leading to benzobicyclo[4,3,0]-compounds, " cyclic ethers " and lactones,and a great many intermolecular reactions, e.g., a [3 -b 3]-annulation of modified t-butyl allylic carbonates and alkylidenemalonitriles to give cyclohexenes,phosphine- (and fluoride)- catalysed routes to 1,4-benzothiazepines from cyclic sulfenamides and alkynes, a [4- -3]-annu-lation of allylic carbonates with methyl coumalate to give functionalised bicyclo[3.2.2]nonadienes, the a-carbon addition of cyanide ion, generated in situ from cyanohydrins, to activated alkynes, and a stereoselective... 

Selenium.—Oxyselenation and halogenoselenation of alkenes using, for example, PhSeCN-ROH or PhSeBr, provide approaches for functionalization of double bonds.Subsequent treatment can remove selenium, or alternatively HBr can be removed to give vinyl selenides. Perhaps the most significant application is the synthesis of cyclic (or bicyclic) ethers and lactones by intramolecular oxyselenation.For example, (78) can be converted into (79) using PhSeBr. 

The cyclization of ort/zo-allyl phenols was reported by Murahashi in the late 1970s. The reaction of the 2-(2-cyclohexenyl)phenol (Equation 16.110) was one of the early examples of Wacker-type reactions with alcohol nucleophiles and has been re-investigated in more recent years with chiral catalysts. Intramolecular reactions of alkene-ols and alkenoic acids form cyclic ethers and lactones. These reactions were reported by Larock and by Annby, Andersson, and co-workers, and examples are shown in Equations 16.111 and 16.112. °° ° The use of DMSO as solvent was important to form the lactone products. More recently, reactions with alcohols were reported by Stoltz to form cyclic ethers by the use of pyridine and related ligands in toluene solvent. - The type of ligand, whether an additive or the solvent, is crucial to the development of these oxidative processes. However, the features of these ligands that lead to catalysis are not well understood at this time. 

---