Asymmetric Syntheses of the Homalium Alkaloids (−)‑(<i>S</i>,<i>S</i>)‑Homaline and (−)‑(<i>R</i>,<i>R</i>)‑Hopromine

The highly diastereoselective conjugate additions of the novel lithium amide reagents lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)­amide and lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)­amide to α,β-unsaturated esters were used as the key steps in syntheses of the homalium alkaloids (−)-(S,S)-homaline and (−)-(R,R)-hopromine. The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps and 18% overall yield, and the asymmetric synthesis of (−)-(R,R)-hopromine was achieved in 9 steps and 23% overall yield, from commercially available starting materials in each case. These syntheses therefore represent by far the most efficient total asymmetric syntheses of these alkaloids reported to date. A sample of the (4′R,4′′S)-epimer of hopromine was also produced using this approach, which provided the first unambiguous confirmation of its absolute configuration and therefore that of natural (−)-(R,R)-hopromine.