Aldehydes are widely utilized as reactive electrophiles to form carbon-carbon bonds. However, it is still difficult to accomplish the perfect chemoselectivity between aromatic and aliphatic aldehydes. We have developed an aromatic aldehyde-selective nucleophilic functionalization via the corresponding pyridinium salt intermediate generated from an aromatic aldehyde with silyl triflate and a pyridine derivative. The pyridinium salt intermediate (A), generated from an aromatic aldehyde (1) in the presence of 2,2’-bipyridyl and TMSOTf, effectively reacted with arenes (Ar1-H) or allylsilanes to produce the corresponding benzyl silyl ethers (3). Meanwhile, an aliphatic aldehyde (2) could also be transformed to the corresponding pyridinium salt intermediates, which were inert toward the nucleophilic attack of arene or allylsilane derivatives resulting to the complete recovery of 2. When using a TMS enol ether (4) derived from an acetaldehyde as a nucleophile, A was smoothly converted to the less reactive pyridinium salt intermediate (B) derived from the aliphatic aldehyde, which was transformed to the β-siloxy aldehyde (5) by aqueous work up. B could be converted to highly-functionalized compounds (6) in a one-pot manner by the continuous addition of a variety of nucleophile such as TMSCN, TMSN3 and allyl-Bpin. The present chemoselective functionalizations are unprecedented and useful to develop a novel strategy for the synthesis of target organic molecules.

Chemoselective functionalization of aromatic aldehyde via pyridinum-type salt intermediate

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.