Lithium chromane

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

Hydrogenation of the carbon-carbon double bond occurs without alteration of the ester function when citronellyl acetate is treated with 2.5 equivalents of trifluoroacetic acid and two equivalents of triethylsilane in 2-nitropropane.205 The reduced product is obtained in 90% yield after 22 hours at room temperature in the presence of one equivalent of added lithium perchlorate (Eq. 82). The yields are lower in the absence of this added salt. Similar reduction of an unsaturated phenolic chroman derivative occurs to give an 85% yield of product with only the carbon-carbon double bond reduced (Eq. 83).205... 

Dihydrobenzopyran (chromane) and its methyl homologs were reduced by lithium in ethylamine and dimethylamine to 3,4,5,6,7,8-hexahydrobenzo-pyrans in 84.5% yields [424. ... 

Several chromans have been synthesized using the Parham cycloalkylation technique (76JOC1184). l-Bromo-3-(2-bromophenoxy)propane, prepared from phenol and 1,3-dibromopropane, is treated with n-butyllithium at — 100 °C. Halogen-lithium exchange yields the aryllithium (278) which cyclizes either at — 100°C or in some instances only at an acceptable rate at higher temperatures. This method offers the advantage of regio-specificity since cyclization is controlled by the location of the o-bromine atom (Scheme 72). 

Methyl ester 431 is tethered by an alkyl chain to an acrylate Michael-acceptor and activated toward decarboxylation by a C-2-ethoxycarbonyl group. As a result of this, chemoselective Sn2-dealkylation of the methyl ester, decarboxylation and cyclization of the enolate by Michael addition occurs upon exposure to lithium chloride in DMEU, affording chroman 432 in excellent yield and diastereoselectivity (Equation 178) <1998JOC144>. 

Tietze and coworkers developed a new total synthesis of vitamin E (1) using a novel enantioselective domino Wacker Heck process as the key step. This allows the formation of the chroman framework 22 with the required i -configuration at the stereogenic center C-2 in 97 % ee with concomitant introduction of part of the vitamin E side chain in 84 % yield. Condensation with (3i )-3,7-dimethyloctanal (21), synthesized from 7 -citronellol (20), followed by reaction with methyl lithium and hydrogenation completed the synthesis. 

Cleavage of Ike tetrahydrochromane (2). Reduction of chromane (1) with a sixfold excess of lithium in ethylamine affords tetrahydrochromane (2) in moderate yield. This substance ii cleaved by m-chloroperbenzoic acid, if in low yield, to the middle-size cyclic ketobtetone (3), of interest because of its relationship to macrolide antibiotic lactones. 

Lithium salts of o-(alk-2-ynyl)phenols and o-(alk-3-ynyl)phenols (preformed through the reaction of phenols with n-butyllithium at 0 °C) react with iodobenzene, 2-iodothiophene, benzyl bromide, and methyl iodide in the presence of a palladium catalyst to give 2-(alkyli-dene)-3-hydrobenzo[ ]furans (Scheme 12) and 2-(alkylidene)chromanes (Scheme 13), respectively. Both palladium diacetate and palladium dichloride have proved effective catalysts, whereas Pd(dba)2 and PdCl2(PPh3)2/DIBAL-H have given very low yields of the desired products. Minor amounts of isomerized products have been obtained by using palladium diacetate or palladium dichloride and triphenylphosphine whereas the employment of Pd(PPh3)4 has been found to afford only the isomerized benzofuran derivative in low yield. 

---