Acetals intermolecular additions

Although the enantioselective intermolecular addition of aliphatic alcohols to meso-epoxides with (salen)metal systems has not been reported, intramolecular asymmetric ring-opening of meso-epoxy alcohols has been demonstrated. By use of monomeric cobalt acetate catalyst 8, several complex cyclic and bicydic products can be accessed in highly enantioenriched form from the readily available meso-epoxy alcohols (Scheme 7.17) [32]. 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

All the examples presented under Sect. 4.1 used an iodine atom transfer to generate the desired radicals. Another approach involving abstraction of hydrogen atom is also reported. For instance, ethers and acetals undergo direct intermolecular addition to aldehydes under treatment with Et3B/air... 

Intermolecular addition and addition-cyclization reactions of aminium cation radicals with electron-rich alkenes such as ethyl vinyl ether (EVE) allow an entry into products containing the N—C—C—O moiety of 13-amino ethers 70 or the equivalent of /3-amino aldehydes 71. The mild conditions under which aminium cation radicals are generated from PTOC carbamates makes the reactions described in Scheme 22 possible. In the absence of hydrogen atom donors, the /3-amino ethoxy(2-pyridylthio) acetal 71 was the major product. The mixed acetal can easily be converted... 

The benzyl anion generated from benzyl chloride gave a low yield of phenyl-acetic acid 305). The radical anion dimer of benzalacetone 75 reacts simultaneously by intramolecular addition to the carbonyl group and intermolecular addition to C02 to the cyclopentane derivative 76 306 (Eq. (135) ). 

Intermolecular addition of carbon nucleophiles to the ri2-pyrrolium complexes has shown limited success because of the decreased reactivity of the iminium moiety coupled with the acidity (pKa 18-20) of the ammine ligands on the osmium, the latter of which prohibits the use of robust nucleophiles. Addition of cyanide ion to the l-methyl-2//-pyr-rolium complex 32 occurs to give the 2-cyano-substituted 3-pyrroline complex 75 as one diastereomer (Figure 15). In contrast, the 1-methyl-3//-pyrrolium species 28, which possesses an acidic C-3-proton in an anti orientation, results in a significant (-30%) amount of deprotonation in addition to the 2-pyrroline complex 78 under the same reaction conditions. Uncharacteristically, 78 is isolated as a 3 2 ratio of isomers, presumably via epimerization at C-2.17 Other potential nucleophiles such as the conjugate base of malononitrile, potassium acetoacetate, and the silyl ketene acetal 2-methoxy-l-methyl-2-(trimethylsiloxy)-l-propene either do not react or result in deprotonation under ambient conditions. 

Unlike many other type of radical addition reactions, the product is most often an alkyl-cobalt(III) species capable of further manipulation. These product Co—C bonds have been converted in good yields to carbon-oxygen (alcohol, acetate), carbon-nitrogen (oxime, amine), carbon-halogen, carbon-sulfur (sulfide, sulfinic acid) and carbon-selenium bonds (equations 179 and 180)354. Exceptions to this rule are the intermolecular additions to electron-deficient olefins, in which the putative organocobalt(III) species eliminates to form an a,/ -unsaturated carbonyl compound or styrene353 or is reduced (under electrochemical conditions) to the alkane (equation 181)355. 

Stereochemistry of addition reactions involving allylsilanes 23.4.12 Intermolecular additions to aldehydes, ketones and acetals... 

The reaction could be extended to )3-hydroxy esters (Scheme 10-115) [144], In this case, TBAF proved the most effective reagent for providing an almost quantitative conversion to the corresponding alkoxysiladioxanes. Activation of the acetal functionality was best achieved with the superacid [TfOH2B(OTf)4], and trapping with allyltrime-thylsilane provided the anti diol products in excellent yield and stereoselectivity. The outcome is in accord with chelation-controlled intermolecular addition with axial attack of the nucleophile onto the cationic oxonium intermediate. 

Oxidative radical cyclization sequences have also been used to generate 1,2-fused indoles. Treatment of amides 152 and 154 with dimethyl methylmalonate in the presence of manganese(III) acetate and sodium acetate in acetic acid, gave the expected cyclized product in 63% and 40%, respectively [97]. The proposed mechanistic sequence involves the intermolecular addition of the dimethyl methylmalonate radical to the tethered exocyclic alkene followed by cyclization and finally rearomatization. Byers and coworkers also achieved a similar cyclization on the C-2 position of the indole when a 3-acylindole was subjected to these oxidative cyclization conditions. 

Intermolecular Additions of Alcohois and Carboxylates The intermolecular oxidations of olefins with alcohols as nucleophile typically generate ketals, whereas the palladium-catalyzed oxidations of olefins with carboxylic acids as nucleophile generates vinylic or allylic carboxylates. As a result, many of the oxidations with alcohols have been conducted with diols to generate stable cyclic acetal products. Both types of oxidations have been conducted on large industrial scale, and vinyl acetate is produced from the oxidative reaction of ethylene with acetic acid in the gas phase over a supported palladium catalyst. ... 

Acetal skeletons are also obtained as products through a highly regio- and diastereoselective intermolecular addition of water and alcohols to alkynyl epoxides catalyzed by gold(I) (Scheme 16) [134, 135]. 

In Fig. 4.6, the titration of p-hydroxybenzoic acid in pyridine shows that the COOH and OH groups can be clearly determined. However, in acetonitrile there is half-way the titration of the COOH group an additional potential jump this can be explained by a phenomenon which was already known for acetic acid23, viz., in the inert solvent acetonitrile intermolecular hydrogen-bridge... 

In continuation of the aforementioned reaction, Hiroya and coworkers used cop-per(II) acetate for the synthesis of indoles 2-943 in reasonable yields from the corresponding ethynylanilines 2-941 by a domino intermolecular Michael addition/cop-per-assisted nucleophilic tosylate displacement reaction via 2-942 (Scheme 2.211) [482],... 

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