Studies toward the Synthesis of Azadirachtin, Part 2: Construction of Fully Functionalized ABCD Ring Frameworks and Unusual Intramolecular Reactions Induced by Close‐Proximity Effects

Abstract

In the preceding Communication in this issue [1] we described the total synthesis of a potential decalin precursor to azadirachtin (1), [2] its coupling to a suitable norbornene fragment 4 (Scheme 1), and the elaboration of the product to an advanced intermediate along the path to this synthetic target. Herein we report the total synthesis and semisynthesis from azadirachtin of a more advanced decalin system 3, its coupling to the same norbornene fragment 4, and the elaboration of the resulting product to an advanced intermediate for the total synthesis of azadirachtin (Scheme 1). This report also includes a number of unusual reactions induced by proximity effects and special steric factors highlighting the unique characteristics of the azadirachtin scaffold.Having successfully synthesized tricyclic decalin system 5, (Scheme 1) and explored its chemistry toward azadirachtin (1) as described in the preceding Communication, [1] we turned our attention to the more advanced tetracyclic decalin precursor 3, which bears the tetrahydrofuran ring system of 1 within its structure. Our plan to synthesize the targeted intermediate 3 required key building block 6 (Scheme 2) as

Tris(trimethylsilyl)silyl versus tris(trimethylsilyl)germyl: Radical reactivity and oxidation ability

“…The solvent used is di-tert-butylperoxide/ benzene (50%/50%) and acetonitrile for the experiments with tBu-O Å and P Å , respectively (see text below). The interaction of (TMS) 3 GeH and (TMS) 3 SiH with a ketone triplet state (benzophenone BP) was studied in benzene; the ketyl radical quantum yield U K . In the case of benzophenone was determined by a classical procedure [8].…”

“…The unique reactivity of tris(trimethylsilyl)silane has also been exploited in cascade reactions leading in a single step to complex molecular scaffolds. Recent elegant examples for nature products synthesis have been also reported [3]. In sharp contrast, tris(trimethylsilyl)germane has been much less exploited in organic synthesis even though its reactivity is slightly superior to n-tributyltin hydride [4].…”

“…The aim of the present paper corresponds to an investigation of the relative reactivity of tris(trimethylsilyl)silane (TMS) 3 Si-H and tris(trimethylsilyl)germane (TMS) 3 Ge-H (Scheme 1); the tris(trimethylsilyl)methane (TMS) 3 C-H is partly introduced for comparison. The formation of the silyl and germyl radicals will be investigated by laser flash photolysis and ESR spin trapping experiments ESR-ST.…”

“…Since its introduction as an efficient radical-based reducing agent more than twenty years ago, tris(trimethylsilyl)silane has found multiple applications in organic synthesis as well as in polymers and materials science [1][2][3][4][5][6][7]. Due to its low toxicity (compared to n-tributyltin hydride) and the very mild reaction conditions, tris(trimethylsilyl)silane has been a reagent of choice for the reduction reaction of organic halides, selenides, activated hydroxy-and carboxy groups even in aqueous media [1e].…”

Transition metals in organic synthesis: Highlights for the year 2005

“…Palladium complexes, together with a hydride source, such as tributyltin hydride, triethylsilane, and triethylamine-formic acid catalyzed the reduction organic bromides, iodides, and triflates. Synthetic applications include, 1,8-naphthyrine C-nucleosides [592], cylindramine [324], azadirachtin [593], dihydroxerulic and xerulinic acid [38], bergapten [594], 3-methoxyelipticine and elipticine [595], (−)-scabronine G [44], (−)-galanthamine and (−)-morphine [447], toward (+)-sorangicin [268], 2-fluoro-11-hydroxy-N-propylnoraporphine [596], hetsine alkaloids [597], pancracine [430] and the DEF-rings of FR182877 [598].…”