Amplification of anti-Diastereoselectivity via Curtin-Hammett Effects in Ruthenium Catalyzed Hydrohydroxyalkylation of 11-Disubstituted Allenes: Diastereoselective Formation of All-Carbon Quaternary Centers

摘要

Under the conditions of ruthenium catalyzed transfer hydrogenation, 1,1-disubstituted allenes >1a–>1c and alcohols >2a–>2g engage in redox-triggered generation of allylruthenium-aldehyde pairs to form products of hydrohydroxyalkylation >3a–>3g, >4a–>4g and >5a–>5g with complete branched regioselectivity. By exploiting Curtin-Hammett effects, good to excellent levels of anti-diastereoselectivity (4:1 – >20:1) are obtained. Thus, all carbon quaternary centers are formed in a diastereoselective fashion upon carbonyl addition from the alcohol oxidation level in the absence of pre-metallated nucleophiles or stoichiometric byproducts. Exposure of allene >1b to equimolar quantities of alcohol >2a and aldehyde >6b under standard reaction conditions delivers adducts >4a and >4b in a 1:1 ratio. Similarly, exposure of allene >1b to equimolar quantities of aldehyde >6a and alcohol >2b provides adducts >4a and >4b in an identical equimolar ratio. Exposure of allene >1b to d2-para-nitrobenzyl alcohol, deuterio->2a, under standard reaction conditions delivers the product of hydrohydroxymethylation deuterio->4a, which incorporates deuterium at the carbinol position (>95% ²H) and the interior vinylic position (34% ²H). Competition experiments involving exposure of allene >1b to equimolar quantities of benzylic alcohols >2a and deuterio->2a reveal no significant kinetic effect. The collective data corroborate rapid, reversible alcohol dehydrogenation, allene hydrometallation and (E)-, (Z)-isomerization of the transient allylruthenium in advance of turn-over limiting carbonyl addition. Notably, analogous allene-aldehyde reductive C-C couplings employing isopropanol as the terminal reductant display poor levels of anti-diastereoselectivity, suggesting carbonyl addition is not turn-over limiting in reactions conducted from the aldehyde oxidation level.