C−H Insertion Approach to the Synthesis of endo,exo-Furofuranones:  Synthesis of (±)-Asarinin, (±)-Epimagnolin A, and (±)-Fargesin

Abstract

A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24, and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified procedure for the Ghosez keteniminium-olefin cyclization was developed, which was required to minimize the decomposition of acid-sensitive functional groups such as electron-rich benzylic ethers that were present in the target compounds 2-4.

Unusual Transformation of Cyclobutenediones into Butenolides

“…Further mechanistic study will be required to elucidate the mechanism. And this process can be used for the synthesis of butenolides, which are found abundantly in nature, [7][8][9] even Scheme 3. Unusual transformation from cyclobutenedione.…”

“…The crude product was heated at reflux in acetonitrile (30 mL) for 2 hrs. After cooling the reaction, the solution was concentrated in vacuo at 50 o C. The resulting residue was purified by flash column chromatography (3/1 hexanes/ethyl acetate) and gave 70 mg (40%) of the desired benzoquinone 23a as a pale yellow liquid: IR (CHCl 3 ) 2955, 2874, 1654, 1608, 1460, 1323, 1249, 1059 cm 8,184.8,156.7,149.9,130.7,125.9,94.9,65.1,61.5,57.6,30.0,28.7,22.4,18.1,13.8,MS (EI), m/z (rel. intensity) 281(4), 208(16), 207(16), 165(14), 137(50), 101(6), 73(100), 58(6); HRMS, m/z calculated for C 18 H 30 SiO 5 , 354.1862;found, 354.1837. 3-Methoxy-6-n-propyl-2-[(trimethylsilylethoxymethoxy)methy]benzoquinone (23b).…”

Functionalization of Carbon–Hydrogen Bonds Through Transition Metal Carbenoid Insertion

“…In systems that already contain stereogenic centers near the site of C-H insertion, that is often enough to control the stereoselectivity of the key carbenoid transformation without the use of a chiral catalyst. That was certainly the case in the synthesis of a variety of endo, exo-furofuranone lignans 186 by Brown and coworkers (Scheme 46, left) [128,129]. Following the synthesis of substrates such as 185 (either racemic or enantioenriched), Rh 2 (OAc) 4 -mediated cyclization furnished a single diastereomer of the bicyclic products 186 in moderate to good yields.…”

Recent Progress in the Chemistry of Keteniminium Salts

“…在此, 我们选取该类反应较为重 要的发展节点, 简明扼要的阐述其发展历程, 总结此类 反应的规律和特点. [35] 、赤霉酸中间体 75 [36] 、前列 腺素内酯(76) [37] 及 3-酰基取代的环丁酮螺环化合物 77 [38] (图 2). Figure 19 Unexpected discovery of cyclization/Claisen rearrangement 随后的研究发现, 除烯丙基以外, 其他能够稳定碳 正离子的取代基如炔丙基、苄基、2-四氢呋喃基、2-四 氢吡喃基等都能参与上述亲电重排反应, 制备一系列 α-烷基取代的内酯化合物 [45,46] (Scheme 20).…”