Ru-Catalyzed Enantioselective Dipolar Cycloadditions of Ethyl Diazopyruvate

Abstract

The decomposition of ethyl diazopyruvate (1) with [RuCl 2 (pybox)] catalysts in the presence of enol ethers affords dihydrofurans derived from formal 1,3-cycloaddition. Enantioselectivities of up to 74% have been achieved.The transition metal-catalyzed decomposition of diazoketones or diazoesters in the presence of olefins affords cyclopropanes. A large variety of catalytic systems, based mainly on copper 1 and rhodium, 2 are available for enantioselective cyclopropanations. Furthermore, diazo compounds carrying electron-accepting substituents such as ethyl diazoacetoacetate, 3 ethyl diazopyruvate, 4 or 2-diazocyclohexane-1,3-dione, 5 or the corresponding phenyliodonium ylides 6 may react with olefins by formal 1,3-cycloaddition to afford dihydrofuran derivatives. The cycloaddition occurs typically with enol ethers, enol acetates, furans and other polarizable olefins, but may also be observed with acetylenes 7 and even with styrene. 8 Pirrung, and subsequently Ishitani and Achiwa, reported enantioselective cycloadditions of 2-diazocyclohexane-1,3-dione or 2-diazodimedone to furan and dihydrofuran, respectively. 9Recently, we have re-examined cycloadditions of 2-diazocyclohexane-1,3-dione to dihydrofuran with a large selection of structurally different chiral rhodium(II) catalysts. 8a,10 However, to our disappointment the reactions proceeded with no, or at best, with very modest enantioselectivity, and we were unable to reproduce the results reported by Pirrung and Ishitani under the conditions used by these authors. This failure was tentatively attributed to the highly electrophilic nature of the intermediate metallocarbene, which is a consequence of the additional electron-withdrawing carbonyl substituent. In contrast, carbenes carrying electron-donating substituents proceed through later transition states as evidenced by their higher r-value in Rh(II)-catalyzed cyclopropanations of styrene, and these latter carbenes are also more enantioselective. 11 Unfortunately, they are in general inappropriate for the preparation of dihydrofurans, although there are exceptions. 12 In view of this, we turned our attention to Ru catalysts. Complexes of ruthenium have been found to catalyze the cyclopropanation of certain olefins effectively, and high levels of asymmetric induction can be realized. Ruthenium has emerged as the third important metal for the carbenoid decomposition of diazo compounds besides copper and rhodium. 13 We were struck by the high r-value of -2.5 for the cyclopropanation of styrene with [RuCl(pnnp)] + reported by Mezzetti. 14 This high negative reaction constant suggested that the Ru complexed carbenes might be more selective than the Rh analogues.Preliminary experiments using 2-diazodimedone as substrate and [RuCl 2 (p-cymene)] 2 in conjunction with Mezzetti's pnnp ligand (7) 14 or with the pybox ligand of Nishiyama 15 were not satisfactory, however. 16 The catalysts were not sufficiently reactive to decompose the diazo precursors efficiently, although encouraging enantioselectivities were obtaine...

Ruthenium-Catalyzed Cycloadditions to Form Five-, Six-, and Seven-Membered Rings

“…145,146 Under optimal conditions, the (3+2) cycloaddition of 2,3-dihydrofuran occurred in good yield, albeit with moderate levels of enantiocontrol. 145 Absolute stereochemistry of the cycloadducts was not determined. In subsequent work, the authors developed ruthenium-catalyzed cycloadditions using phenyliodonium ylides as carbene precursors; however, low yields and negligible levels of enantioselectivity were observed (not shown).…”

“…In 2004, Chappellet and Müller reported enantioselective (3+2) cycloadditions of ethyl diazopyruvate with enol ethers using a PyBOX-modified ruthenium catalyst (Scheme ). , Under optimal conditions, the (3+2) cycloaddition of 2,3-dihydrofuran occurred in good yield, albeit with moderate levels of enantiocontrol . Absolute stereochemistry of the cycloadducts was not determined.…”

SENSITIVE SIMULTANEOUS DETERMINATION OF PARACETAMOL AND DICLOFENAC BASED ON Au NANOPARTICLES - FUNCTIONALIZED GRAPHENE/POLY (L-ARGININE) GLASSY CARBON ELECTRODE

“…5 In addition to that these are having many applications in dyes preparation, chemically controllable switches, efficient electroluminescent materials, dehydroannulenes, and inorganic semiconductors. [6][7][8][9][10][11] Quinoxaline ring moiety comprise part of the chemical structures of various antibiotics such as Echinomycin, Levomycin and Actinoleutin 12,13 , that are known to inhibit growth of gram positive bacteria and are also active against various transplantable tumors.…”