Reaction of Acetals with Various Carbon Nucleophiles under Non‐Acidic Conditions: CC Bond Formation via a Pyridinium‐Type Salt

Abstract

Mild substitution reactions of acetals with carbon nucleophiles via the pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6-collidine or 2,2'-bipyridyl have been developed. Various carbon nucleophiles, such as organocuprates, silyl enol ethers, enamines, etc., reacted with the pyridinium-type salts to give the corresponding substituted products in good yields. The reactions proceeded under very mild conditions (non-acidic conditions) and thus acid-sensitive functional groups can be tolerated during the reaction. In addition, only an acetal can form the pyridinium-type salt and react with nucleophiles in the presence of a ketal. This unusual selectivity is in contrast to general methods conducted under acidic conditions.

Palladium on Carbon‐Catalyzed Benzylic Methoxylation for Synthesis of Mixed Acetals and Orthoesters

“…Chemical modifications of the mixed acetals and orthoesters were also investigated (Scheme ). The methoxy group of 2 e and 2 h could be chemoselectively activated using a combination of triethylsilyl trifluoromethanesulfonate (TESOTf) and 2,4,6‐collidine, and the subsequent nucleophilic substitution using 1‐phenyl‐1‐trimethylsiloxyethylene gave 5 e and 5 h in good yields. It is noteworthy that the orthoester ( 2′a ) was also transformed into the corresponding ketal ( 5′a ) in 69 % yield under similar conditions.…”

“…The methoxy group of 2e and 2h could be chemoselectively activated using ac ombination of triethylsilyl trifluoromethanesulfonate( TESOTf) and 2,4,6-collidine, [20] and the subsequent nucleophilic substitution using 1-phenyl-1-trimethylsiloxyethylene gave 5e and 5h in good yields. The methoxy group of 2e and 2h could be chemoselectively activated using ac ombination of triethylsilyl trifluoromethanesulfonate( TESOTf) and 2,4,6-collidine, [20] and the subsequent nucleophilic substitution using 1-phenyl-1-trimethylsiloxyethylene gave 5e and 5h in good yields.…”

Oxidation of Secondary Methyl Ethers to Ketones

“…2-Methoxyundecane (8). 15 Sodium hydride (865 mg, 21.6 mmol, 1.5 equiv, 60% dispersion in mineral oil) was added at 0 °C to a solution of undecan-2-ol 42 (2.48 g, 14.4 mmol, 1.0 equiv) in THF (20 mL). The mixture was stirred for 30 min; then methyl iodide (1.35 mL, 21.6 mmol, 1.5 equiv) was added.…”

Chemoselective Nucleophilic Functionalizations of Aromatic Aldehydes and Acetals via Pyridinium Salt Intermediates

“…Acetals are generally and frequently utilized as protecting groups of aldehydes, and the direct functionalizations without the deprotection steps were sometimes powerful tools to effectively synthesize the target molecules. , Although the reactivities of the pyridinium salt intermediates derived from acetals, SiOTf, and adequate pyridine derivatives have already been reported, the reaction with arenes, allylsilanes, or silyl enol ethers derived from acetaldehyde as nucleophiles has never been reported in the literature. The reaction with the pyridinium salt ( D ) derived from benzaldehyde ethylene glycol acetal derivatives ( 6a and 6b ), TESOTf, and 2,2′-bipyridyl could react with 1,3,5-trimethoxybenzene to produce the desired ethylene glycol asymmetric ether products ( 7a and 7b ) (Table , entries 1 and 2).…”