Diastereo- and Enantioselective Synthesis of 2,2-Disubstituted Benzofuran-3-one Bearing Adjacent Quaternary and Tertiary Stereocenters

Abstract

The first highly diastereo- and enantioselective synthesis of armeniaspirol analogues was achieved using L-proline derived bifunctional squaramide which outperformed commonly used organocatalysts. Excellent yield (up to 99%) with diastereoselectivity (up to 99:1) and enantioselectivity (up to 99%) were obtained for a wide range of substrates.

Total synthesis and mechanism of action of the antibiotic armeniaspirol A

“…While attempts with oxone, sodium chlorite/t-BuOOH, pyridinium chlorochromate, potassium persulfate or mCPBA either led to decomposition or to unreacted starting material, the use of DDQ (1.2 eq) at room temperature in an acetonitrile/water mixture gave (±) armeniaspirol A in a yield of 45% (Table 2). The structural identity was proven by 13 C-and 1 H-NMR data and by mixing experiments with natural 1. In summary, we report a short, elegant synthesis of racemic armeniaspirol A, that is six steps overall from commercial starting materials and an overall yield of 20.3% in the longest linear sequence.…”

“…The synthesis was short (7 steps, 13.8% overall yield), but the oxidative chlorination conditions led to chloroarmeniaspirol 4 rather than the natural product itself, as the chlorination at the pyrrole ring was inevitably associated with an undesired chlorination at the electron-rich C2 position. Recent studies of Sivamuthuraman et al as well as Huang et al showed elegant routes to armeniaspirol-like or -inspired scaffolds, that were however functionalized differently; 13,14 antibiotic activity of those compounds was not reported.…”

Asymmetric Michael Addition of Unactivated Ketones with β‐Nitrostyrenes Mediated by Bifunctional L‐Prolinamide Organocatalysts

“…Michael addition named after Arthur Michael has been known for carbon‐carbon bond formation through conjugate addition of carbanion to α, β‐unsaturated compound in organic synthesis . Resulting Michael adducts serve as key intermediates in total synthesis of various biologically active natural products such as neuropharmacology active (−)‐α‐kainic acid, pregnane steroid hormone Cortisone, antimicrobial compound Claenone, Culmorin, Valeriananoids A, B, and C, (−)‐Epibatidine, Chromenone, Nhatrangin, Armeniaspirol etc . Apart from these, Michael adducts also signify a convenient route for the synthesis of γ‐nitro carbonyl, the nitro group of these carbonyl compounds can further be transformed into an amine, ketone, nitrile oxide, oxime etc…”

Squaramide‐Linked Chloramphenicol Base Hybrid Catalysts for the Asymmetric Michael Addition of 2,3‐Dihydrobenzofuran‐2‐carboxylates to Nitroolefins

“…Herein, we report a novel array of hybrid organocatalysts by assembling chloramphenicol base with a chiral amine scaffold through a squaramide linker . Assessment of the catalytic behavior of these hybrids in the asymmetric Michael addition of 2,3‐dihydrobenzofuran‐2‐carboxylates to nitroolefins with the formation of a quaternary stereocenter at the C‐2 position is also described . Notably, the hybrid catalysts gave higher stereoselectivity and efficiency than single‐chiral‐scaffold‐derived bifunctional catalysts through control experiments.…”