anti ‐Configured 1,3‐dimethyl deoxypropionate motifs are important sub structures in natural products. Herein, we describe a bidirectional approach for the rapid construction of natural products featuring such motifs by using C 2 ‐symmetrical 1,3‐bis(boronic esters). As for its application in convergent syntheses it was important to establish a selective mono‐Zweifel olefination we describe the scope and limitations by using different 1,3‐bis(boronic esters) and nucleophiles. This protocol takes advantage of the combination of the Hoppe–Matteson–Zweifel chemistry, which was elegantly put into practice by Aggarwal et al. In order to show its applicability the total syntheses of two natural products, serricornin and (+)‐invictolide, were performed.

The first total synthesis of chondrochloren A is accomplished using a 1,2-metallate rearrangement addition as an alternative for the Nozaki-Hiyama-Kishi reaction. This transformation also avoids the inherent challenges of this polyketide segment and provides a new, unprecedented strategy to assemble polyketidal frameworks. The formation of the Zenamide is accomplished using a Z-selective cross coupling of the corresponding amide to a Z-vinyl bromide.

Stereotriads bearing allylic alcohols are privileged structures in natural products, and new methods accessing these in a stereoselective fashion are highly sought after. Toward this goal, we found that the use of chiral polyketide fragments allows for performing the Hoppe−Matteson−Aggarwal rearrangement in the absence of sparteine with high yields and diastereoselectivities, rendering this protocol a highly valuable alternative to the Nozaki−Hiyama−Takai− Kishi reaction. The switch of directing groups in most cases resulted in the reversed stereochemical outcome, which could be explained by conformational analysis on density functional theory level and a Felkin-like model.

Anti-configured 1,3-dimethyl deoxypropionate motifs are important sub-structures in natural products. We describe a bidirectional approach for the rapid construction of highly reduced polyketide fragments for the synthesis of georatusin employing our mono-Zweifel protocol.

The first total synthesis of pericoannosin A (1) containing 15 steps in the longest linear sequence with an overall yield of 5.5% is reported. The hybrid peptide-polyketide was isolated from the endophytic fungus Periconia sp. F-31 and bears a unique tricyclic core structure. The key steps are a glycolate aldol reaction and a Diels-Alder reaction utilizing an Evans auxiliary for controlling the stereochemistry. Furthermore, a late-stage equilibration was employed.