Enantioselective Total Synthesis of (+)-Salimabromide Reveals Almost Racemic Nature of Natural Salimabromide

Abstract

The enantioselective total synthesis of (+)-salimabromide was accomplished by a concise two-step conversion of the fully functionalized dibromo-tetraline core, involving a one-pot Baeyer–Villiger/allylic oxidation by an innovative radical reagent combination. This route unequivocally resolves the stereochemistry and reveals the highly unusual, almost racemic nature of natural salimabromide.

Dihydroxylation Studies of Isoquinolinones: Synthesis of the EF-Ring of Lysolipin I

“…[9,29] In agreement with this observation, a broad range of wellestablished protocols for dihydroxylations and epoxidations, including Sharpless asymmetric dihydroxylations [25] (entry 1, Table 1), variations of the Upjohn protocol [26] (entries 2-4) or the Woodward dihydroxylation (Sudalai modification: entry 5) [27,28] proved unsuccessful resulting mainly in no or very low degrees of conversion. Similarly, hydroxylations of electron rich 7,8-dihydroxylated isoquinolinones (11)(12)(13) proved not promising. Also, various epoxidation reagents did not result in any conversions, including mCPBA [30] , H 2 O 2 [31] , oxone [32] or the Jacobsen procedure (not shown).…”

“…While various strategies for synthesis of the parent isoquinolinones are available, [6,7,8] selective hydoxylation reactions for specific introduction of an oxygenation pattern have hardly been advanced. [9] As part of our studies to develop new approaches for highly unsaturated polyketide antibiotics, [10][11][12][13][14][15][16] we report herein a general study on asymmetric benzylic dihydroxylations of various isoquinolinones (3), which differ in the substitution and protective group pattern at C6 and C7 of the appending aromatic ring. Finally, we apply this strategy for preparation of the authentic EF-ring system of lysolipin I.…”

Oxetane Intermediate during a Direct Aldol Reaction: Stereoselective [5 + 1] Annulation Affording Tetralines

“…The scope of the tetraline formation was explored with respect to the combination of aldehydes and the substrates 3 (Scheme ). , Electron-withdrawing and electron-donating substituents at the para position of benzaldehyde were performed for the [5 + 1] annulation with 3a to yield 4ab – 4ah . Meta- and ortho-substituted benzaldehydes yielded 4ai – 4an .…”