Total Synthesis of Cryptocaryol A by Enantioselective Iridium‐Catalyzed Alcohol C−H Allylation

Abstract

The polyketide natural product cryptocaryol A is prepared in 8 steps via iridium catalyzed enantioselective diol double C−H allylation, which directly generates an acetate‐based triketide stereodiad. In 4 previously reported total syntheses, 17–28 steps were required.

Total Synthesis of Sanctolide A and Formal Synthesis of (2S)-Sanctolide A

“…The addition of the vinyl Grignard to diepoxide ( R , R )- 16 , in the presence of catalytic CuCN, delivered the homoallylic diene-diol ( S , S )- 8 in 70% yield . In addition, ( S , S )- 8 was generated in a more direct atom- and step-economical fashion from commercially available 1,3-propanediol by utilizing the Krische Ir-catalyzed transfer hydrogenation allylation method …”

“…The first step of the telescoped one-pot protocol involves an RCM reaction to generate a P -stereogenic bicyclo[5.3.1]­phosphate bearing a trisubstituted olefin, which undergoes CM and then a substrate-controlled diastereoselective per hydrogenation to set the C2 stereocenter before P -tether removal . The respective pseudo C 2 -symmetric triene can be readily prepared in two steps from ( S , S )- 8 , which is derived from 1,3-propanediol in one step utilizing the Krische allylation method . Taken collectively, this step-economical protocol would introduce a modular synthetic route to the existing synthesis with improved atom economy in which a complete conversion of the triene was expected after the RCM/CM/H 2 sequence utilizing cis -3-hexene as the CM partner.…”

Feedstock Reagents in Metal‐Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target‐Oriented Synthesis

“…The same C 2 ‐symmetric diol previously required a seven‐step synthesis involving three protecting group manipulations, two separate alcohol oxidations, and two separate carbonyl asymmetric allylborations . As illustrated in concise total syntheses of (+)‐roxaticin, bryostatin 7, cryptocaryol, mandelalide (not shown), and neopeltolide (not shown), this C 2 ‐symmetric diol serves as a powerful building block for polyketide construction. Neopentyl glycol (6.8×10 5 tons yr −1 ) is used extensively in the paints and coatings industry.…”

Insights into the Palladium(II)-Catalyzed Wacker-Type Oxidation of Styrene with Hydrogen Peroxide and tert-Butyl Hydroperoxide

“…Significant strides were made when Sigman and co-workers developed synthetic methods using TBHP as an oxidant. Their approach consisted of reacting a quinoline-2-oxazoline (Quinox) ligand with PdCl 2 to generate, in situ, a dicationic complex in the presence of Ag­[SbF 6 ], allowing the oxidation of a range of alkenes to their desired ketones in excellent yields. − Furthermore, this TBHP catalyst system often outperforms aerobic methods and has been applied in target-orientated synthesis studies. − …”