Ruthenium(II)-Catalyzed Site-Selective Hydroxymethylation of Indolines with Paraformaldehyde

Abstract

The facile synthesis of hydroxymethylated indole derivatives is crucial for their further development as pharmaceutical compounds and other synthetic purposes. Herein, we describe the ruthenium­(II)-catalyzed hydroxymethylation of indolines and other N-heterocycles using paraformaldehyde as an abundant C1 feedstock. A wide substrate scope range and high levels of site selectivity as well as functional group tolerance were observed.

Ru(II)-Catalyzed C–H Hydroxyalkylation and Mitsunobu Cyclization of N-Aryl Phthalazinones

“…Moreover, electron-deficient aryl aldehydes 2b – 2f were compatible for this transformation to generate the corresponding products 3o – 3s . Paraformaldehyde 2g as an abundant one-carbon feedstock was also exploited in the Ru­(II)-catalyzed hydroxymethylation reaction to provide 3t in 42% yield under the current reaction conditions. It is noted that electron-rich (hetero)­aryl aldehydes (2-thiophenecarboxaldehyde, p -anisaldehyde), enal ( trans -cinnamaldehyde), aliphatic aldehydes ( n -hexanal, cyclohexanecarboxaldehyde), and benzylic aldehyde (2-phenylacetaldehyde) provided unsatisfactory results (<10% yield) under the current reaction conditions (data not shown).…”

Nickel-Catalyzed Tandem Cyclization of 1,6-Diynes with Indolines/Indoles through Dual C–H Bond Activation

“…Abbreviations for signal coupling are as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Starting materials 1-(pyridin-2-yl)­indolines 1 , 1-(pyridin-2-yl)-1 H -indole 4, and diynes 2a – e − 2f were prepared according to literature procedures. Commercially available chemicals were purchased from Sigma-Aldrich and Spectrochem.…”

Experimental and density functional theory studies on hydroxymethylation of phenylboronic acids with paraformaldehyde over a RhPPh3 catalyst

“…Benzyl alcohol (BA) derivatives are kinds of valuable building blocks in organic synthesis and fine‐chemical industries such as cosmetics, dyes, coatings, inks, and polymers. [ 1–4 ] BA is also an important structural motif in many bioactive natural products and pharmaceuticals. [ 5,6 ] For example, benzyl benzoate, salix, and beneate hydrochloride contain the BA motif, which are widely used in anti‐infective for dermatology, [ 7 ] antipyretic analgesia, [ 8 ] and treatment of ulcer disease, [ 9 ] respectively (Figure 1).…”