Stereoselective Epoxide Generation with Cyclic Rhodium Carbenoids: A New Access to Spiro-indolooxiranes

Abstract

The reaction of cyclic diazoamides with aryl aldehydes catalyzed by rhodium(II) acetate leads to intermolecular stereoselective epoxide ring formation. A series of spiro-indolooxiranes has been synthesized following the described method in a facile manner. The use of aryl dialdehydes in the course of reaction of cyclic diazoamide resulted the formation of bis-spiro-indolooxiranes Diazo moiety has become a key component in a number of synthetic transformations since from the first recorded synthesis of a-diazo carbonyl compound by Curtius 1 in 1883. The emergence of diazo carbonyl compounds as useful precursors in organic synthesis can be traced to their ready participation in cyclopropanation, insertion reactions and ylide formation upon exposure to transition metal catalysts. 2 The metal-carbenoid generated transient ylides can undergo 1,3-dipolar cycloaddition reaction with a range of dipolarophiles, rearrangement reactions or cyclization to three-membered ring (aziridine or epoxide formation). The cyclization of transition metal generated carbonyl ylides, in principle, can deliver the oxirane ring systems. However, the literature reports 2,3 on carbonyl ylides are dominated by 1,3-dipolar cycloaddition reactions rather than the formation of the oxirane ring system. Originally, Huisgen reported 4 that the formation of 7% oxirane in the reaction between dimethyl diazomalonate and benzaldehyde catalyzed by Cu(acac) 2 . But the formation of oxirane was not observed when the reaction was catalyzed by Rh 2 (OAc) 4 . The rhodium(II)-catalyzed decomposition of ethyl diazoacetate in the presence of aldehydes furnished dioxolanes (by means of 1,3-dipolar cycloaddition of the carbonyl ylide intermediate with a second equivalent of aldehyde) and did not produce oxiranes. 5Despite the commonality and selectivity (vide infra) of rhodium(II) acetate catalyzed reactions of diazo carbonyl compounds, they were not found to produce the oxirane ring systems until the recent report by Doyle 6 and followed by Davies. 7 In an alternative route, Aggarwal delineated a useful method 8 for the formation of oxirane by intercepting the metal carbene with alkyl sulfide. Recently, we have been extensively involved in developing new synthetic strategies 9 using diazo carbonyl compounds. The reactivity of cyclic diazo ketones and amides was studied with olefins and heteroaromatic dipolarophiles to furnish cyclopropanation, 10 C-H insertion 11 or cycloadducts 12 via 1,3-dipolar cycloaddition reactions. To the best of our knowledge, only simple acyclic diazo carbonyl compounds have been used in the epoxide generation, which mainly led to the benzylidene or methylidene transfer. Continuing our interest in the reactions of cyclic diazoamides 10,11 and motivated by the recent reports, 6,7 we herein delineate the rhodium(II) acetate catalyzed reaction of cyclic diazoamides with aryl aldehydes that leads to the stereoselective construction of spirocyclic oxiranes. Figure 1Initially, we planned to study the reactions of cyclic diazoamides 1 (Figure ...

The Epoxidation of Carbonyl Compounds with a Benzyne-Triggered Sulfur Ylide

“…Other sulfoxides 3a – d , 3m , and 3n led to both diastereoisomeric epoxides in roughly equal yields. The stereochemistry of these epoxides was readily determined by examination of the NMR spectra (HMQC and two-dimensional (2D) 1 H– 1 H NOESY) for the corresponding cis and trans isomers, consistent with literature examples. ,− The epoxidation of N -methyl isatin 2 with benzyne-triggered sulfur ylides proceeded efficiently in sulfoxides containing a benzylic group with both electron-withdrawing (Table , 3b – g , 3i , and 3j ) and electron-donating (Table , 3k – n ) substituents. Functional groups such as fluoro, chloro, bromo, nitro, cyano, methoxy, and naphthyl groups were tolerated under the reaction conditions.…”

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