Solution‐Phase Mixture Synthesis with Fluorous Tagging En Route: Total Synthesis of an Eight‐Member Stereoisomer Library of Passifloricins

Abstract

Double your pleasure: A new double‐tagging approach is validated by making eight individual stereoisomers of passifloricin through the intermediacy of a pair of four‐compound quasi‐isomeric mixtures.

Making Mixtures to Solve Structures: Structural Elucidation via Combinatorial Synthesis

“…An initial attempt at the synthesis of 21 began with the conjugate addition of the cuprate derived from 2-hexylmagnesium bromide (17) with methyl methacrylate (Scheme 4). Preparation of the Grignard was complicated by formation of the homocoupled product 18 unless highly activated magnesium was used at 0°C or lower.…”

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…The synthesis contrasted with all prior mixture work, in which building blocks with coded stereocenters were premade and pretagged. 290 The allylation−oxidation protocol was also used by Cossy and BouzBouz in the stereoselective synthesis of (+)-strictifolione, a natural product isolated from Cryptocarya strictifolia, which has been shown to display antifungal activity. 291 In this case, they performed three allyltitanations with both enantiomers of 22a in high yields and stereoselectivities to establish the stereochemistry at C5, C9, and C11.…”

Synthesis of the debrominated analog of dihydroflustramine C utilizing a sulfur ylide-initiated thio-Claisen rearrangement

“…We envisioned that the incorporation of an olefin into the vinyldiazoester coupling precursor would give the desired product after ring-closing metathesis (RCM). 12 With this as a goal, the Rh 2 (OAc) 4 catalyzed coupling of 12 with vinyl diazoacetates 21 and 22 gave indolines 24 and 25, respectively. Unfortunately, all attempts at RCM using the 2 nd generation Grubbs catalyst 26 were completely unsuccessful here.…”

“…Of note was that a similar sequence had been employed by Crich during his syntheses of debromoflustramine B and pseudophyryaminol. 12 With the Crich precedent in mind, we became interested in carrying out the oxidative fragmentation chemistry on pyrrolo-indoline 27 whose synthesis in a single step from the reaction of 17 with LiAlH 4 is illustrated in Scheme 6. This highly efficient reaction involved the reduction of the ester and formamide, along with a subsequent cyclization and reduction of the resulting amidine.…”