Question

What was the first demonstration of organic total synthesis?

Answer 1

The first total synthesis was the Finnish chemist Gustav Komppa's total synthesis of camphor.

Explanation:

In 1903, Komppa succeeded in synthesizing camphoric acid from diethyl oxalate and diethyl β,β-dimethylglutarate.

A few years earlier, Haller and Blanc had converted camphoric acid to camphor, so this constituted a total synthesis of camphor.

At the time, camphor was a scarce natural product with a worldwide demand.

Komppa realized this and began industrial production of camphor in 1907.

For the terminally curious, here's a summary of the steps.

`underbrace(("COOCH"_2"CH"_3)_2)_color(red)("diethyl oxalate") + underbrace(("CH"_3)_2"C"("CH"_2"COOCH"_2"CH"_3)_2)_color(red)("diethyl β,β-dimethylglutarate") stackrelcolor(blue)("NaOEt"color(white)(X))(→)`

diethyl diketocamphorate (I)

`"CH"_3"I/Na" →`

`"Zn/HCl →"`

`"HI/red P" →`

`"HBr" →`

`"Zn/HCl" →`

`"Acetic anhydride, Δ" →`

`"Na(Hg)" →`

`"KCN"`

`"OH"^("-")("aq"), Δ →`

`"Ca salt", Δ →`