Synthesis Golf V: Denopamine
OK, new route. Retrosynthesis:



Denopamine 1 can be made by a reductive amination between amine 2 and aldehyde 3 (either of the two reductive amination disconnections are fairly obvious choices).

The requisite amine 2 contains 10 carbons and so it becomes necessary to make it using some other means - in this case, reduction of a nitroolefin 4, which can itself be made via a nitroaldol reaction from 3,4-dimethoxybenzaldehyde 5 and nitromethane 6.

The chiral α-hydroxyketone 3 can probably be made in numerous ways. Earlier I proposed organoocatalytic oxygenation with PhNO, but another possibility is to have an addition of "formaldehyde anion" to 4-hydroxybenzaldehyde 7. Nitromethane 6 was chosen as the acyl anion equivalent, as the asymmetric Henry reaction is well-established methodology, e.g. by the Evans group (J. Am. Chem. Soc. 2003, 125 (42), 12692–12693).

The forward synthesis is fairly straightforward:







5 steps from cheap starting materials, with longest linear sequence being 3 steps.