Ruthenium-catalyzed reductive couplings of paraformaldehyde with dienes, alkynes, and allenes provide access to products of hydrohydroxymethylation that cannot be formed selectively under the conditions of hydroformylation. In certain cases, the regioselectivity of the CC coupling can be inverted by using nickel catalysts. With iridium catalysts, methanol engages in redox-neutral regioselective hydrohydroxymethylations.

The regioselective reductive coupling of paraformaldehyde to 2-substituted dienes at positions C1, C2 and C3 was achieved using metal catalysts based on nickel, cationic ruthenium and neutral ruthenium, respectively. Whilst C1 adducts predominate using dienes, silicon-or tin-substituted dienes exhibit C4 regioselectivity -the first time that this regioselectivity has been observed for the coupling of 2-substituted butadienes to aldehydes. Both nickel-and ruthenium-catalyzed processes avoid pyrophoric or mass intensive reducing agents, using paraformaldehyde or isopropanol, respectively. These couplings may be viewed as alternatives to diene hydroformylation, for which regioselective formation of constitutionally isomeric products has not yet been achieved.

Ruthenium(II)-catalyzed hydrogen transfer from 2-propanol mediates reductive coupling of 1,1-disubstituted allenes with formaldimines with complete branch-regioselectivity, thus representing a new method for hydroaminomethylation beyond classical hydroformylation/reductive amination.

Trifluoromethyl substituted allenes engage in ruthenium catalyzed reductive couplings with paraformaldehyde to form products of hydrohydroxymethylation as single regioisomers. This method enables generation of CF3-bearing all-carbon quaternary stereocenters.

Alcohol is the Answer! Ruthenium(II) complexes catalyze the C-C coupling of 1,1-disubstituted allenes and fluorinated alcohols to form homoallylic alcohols bearing all-carbon quaternary centers with good to complete levels of diastereoselectivity. Whereas fluorinated alcohols are relatively abundant and tractable, the corresponding aldehydes are often not commercially available due to their instability.