One-step catalytic asymmetric synthesis of all-syn deoxypropionate motif from propylene: Total synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid

Significance Synthetic strategies for deoxypropionate motif reported to date mainly use iterative elongations, thus requiring many reaction steps to obtain the desired natural product. Additionally, such methods also require the preparation of complex building blocks. Here, we have developed a one-step construction of deoxypropionate motif by stereo-controlled propylene oligomerization. Our method using propylene as a very simple building block provides the shortest, three-step access to a natural product whose preparation conventionally required at least 10 steps. Furthermore, multiple oligomers with different number of deoxypropionate units can be isolated from the same oligomerization product, enabling the construction of library. Because deoxypropionate motif is found in a variety of biologically active compounds, our method would impact the field of synthetic organic chemistry. In nature, many complex structures are assembled from simple molecules by a series of tailored enzyme-catalyzed reactions. One representative example is the deoxypropionate motif, an alternately methylated alkyl chain containing multiple stereogenic centers, which is biosynthesized by a series of enzymatic reactions from simple building blocks. In organic synthesis, however, the majority of the reported routes require the syntheses of complex building blocks. Furthermore, multistep reactions with individual purifications are required at each elongation. Here we show the construction of the deoxypropionate structure from propylene in a single step to achieve a three-step synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid, a major acid component of a preen-gland wax of the graylag goose. To realize this strategy, we focused on the coordinative chain transfer polymerization and optimized the reaction condition to afford a stereo-controlled oligomer, which is contrastive to the other synthetic strategies developed to date that require 3–6 steps per unit, with unavoidable byproduct generation. Furthermore, multiple oligomers with different number of deoxypropionate units were isolated from one batch, showing application to the construction of library. Our strategy opens the door for facile synthetic routes toward other natural products that share the deoxypropionate motif.