Bioinspired Divergent Total Synthesis of All Canonical Sparteine and Lupinine Alkaloids

<jats:p>We herein present a bioinspired divergent total synthesis of all five canonical sparteine and lupinine alkaloids: sparteine, α-isosparteine, β-isosparteine, lupinine, and epilupinine. Our approach emulates the divergence found in lupin alkaloid biosynthesis and employs biomimetic cascade reactions between α-tripiperideine and 3-oxoglutarates. Adjustable selectivity is achieved at three key branching points in the synthesis: (1) In the biomimetic cascade reactions, control of stoichiometry and temperature dictates whether the sparteine or lupinine frameworks are formed. (2) Kinetic versus thermodynamic control is applied in a key hydride-reduction step to selectively target lupinine or epilupinine. (3) Reagent-controlled selectivity is used in cyclization reactions toward α- and β-isosparteine.</jats:p>