Asymmetric Total Synthesis and Absolute Configuration Determination of (−)-Verrupyrroloindoline

The first asymmetric total synthesis of (−)-verrupyrroloindoline (20% overall yield in 6 steps) is described. The short approach was enabled by Buchwald’s Cu­(II)-catalyzed asymmetric conjugate reduction, DMDO-triggered one-pot four-step tandem reaction, and the first amide-selective Ir-catalyzed direct reduction of β-carboethoxy tertiary lactam. Along with the total synthesis, the absolute configuration of natural verrupyrroloindoline was determined as 7<i>R</i>,10<i>R</i>,11<i>R</i>

Radical Migration–Addition of <i>N</i>-<i>tert-</i>Butanesulfinyl Imines with Organozinc Reagents

A novel migration–addition sequence was discovered for the reaction of enantioenriched <i>N</i>-<i>tert</i>-butanesulfinyl iminoacetate <b>1a</b> with functionalized benzylzinc bromide reagents, producing <i>tert</i>-leucine derivatives in excellent diastereoselectivity (dr 98:2). The absolute configurations of two new chiral centers were unambiguously assigned by chemical transformations and X-ray crystallography. In addition, the regio- and diastereoselectivities of this novel reaction were both explained through the key <i>N</i>-sulfinamine intermediate <b>M6</b> generated by the <i>tert</i>-butyl radical attack on the imine. Computational analysis of this reaction process, which was performed at the B3LYP/6-311++G­(3df,2p)//B3LYP/6-31G*-LANL2DZ level, also supported our proposed two-stage mechanism

Radical Migration–Addition of <i>N</i>-<i>tert-</i>Butanesulfinyl Imines with Organozinc Reagents

A novel migration–addition sequence was discovered for the reaction of enantioenriched <i>N</i>-<i>tert</i>-butanesulfinyl iminoacetate <b>1a</b> with functionalized benzylzinc bromide reagents, producing <i>tert</i>-leucine derivatives in excellent diastereoselectivity (dr 98:2). The absolute configurations of two new chiral centers were unambiguously assigned by chemical transformations and X-ray crystallography. In addition, the regio- and diastereoselectivities of this novel reaction were both explained through the key <i>N</i>-sulfinamine intermediate <b>M6</b> generated by the <i>tert</i>-butyl radical attack on the imine. Computational analysis of this reaction process, which was performed at the B3LYP/6-311++G­(3df,2p)//B3LYP/6-31G*-LANL2DZ level, also supported our proposed two-stage mechanism

Total Synthesis of (−)-Sessilifoliamide J

An efficient synthesis of the <i>Stemona</i> alkaloid (−)-sessilifoliamide J (<b>1</b>) in 12 steps and 7.7% overall yield from the known building block <b>8</b> is presented. The synthesis features the Corey lactonization reaction and a highly diastereoselective α-methylation reaction to build the spiro-lactone moiety