Rhodium(I)-Catalyzed Nucleophilic Ring-Opening Reactions of Oxabicyclo Adducts Derived from the [4 + 2]-Cycloaddition of 2-Imido-Substituted Furans

Abstract

A series of 2-imido substituted furans containing tethered unsaturation were prepared by the addition of the lithium carbamate of furan-2-yl carbamic acid tert-butyl ester to a solution of the mixed anhydride of an appropriately substituted 3-butenoic acid. The initially formed imido furans undergo a rapid intramolecular [4+2]-cycloaddition at room temperature to deliver the Diels-Alder cycloadducts in good to excellent yield. Isolation of the highly labile oxabicyclic adduct is believed to be a consequence of the lower reaction temperatures employed as well as the presence of the extra carbonyl group, which diminishes the basicity of the nitrogen atom thereby retarding the ring cleavage/rearrangement reaction generally encountered with related systems. By using a Rh(I)-catalyzed ring opening of the oxabicyclic adduct with various nucleophilic reagents, it was possible to prepare highly functionalized hexahydro-1 H-indol-2(3H)-one derivatives in good yield. The major stereoisomer obtained possesses a cis-relationship between the nucleophile and hydroxyl group in the ring-opened product. The stereochemistry was unequivocally established by X-ray crystallographic analysis. Coordination of Rh(I) to the alkenyl π-bond followed by a nitrogen-assisted cleavage of the carbon-oxygen bond occurs to furnish a π-allyl rhodium(III) species. Addition of the nucleophile then occurs from the least hindered terminus of the resulting π-allyl rhodium(III) complex. Proton exchange followed by rhodium(I) decomplexation ultimately leads to the cisdiastereomer.

Synthesis of the Tetracyclic Framework of the Erythrina Alkaloids Using a [4 + 2]-Cycloaddition/Rh(I)-Catalyzed Cascade of 2-Imidofurans

“…29 The isolation of the somewhat labile (acid, heat) oxabicyclo adduct 5a was attributed to the low reaction temperature employed as well as the presence of the carbonyl group, which diminished the basicity of the nitrogen atom thereby retarding the ring cleavage/rearrangement reaction generally encountered with related furanyl carbamates. 30 The facility of the cycloaddition was also shown to be due to the placement of the carbonyl center within the dienophile tether 31 as well as the presence of the carbomethoxy group which lowers the LUMO energy of the π-bond, thereby facilitating the cycloaddition.…”

Synthesis of the Tetracyclic ABCD Ring Domain of Calyciphylline A-Type Alkaloids via Reductive Radical Cyclizations

“…Treatment of ketone 5 with benzylamine under Dean–Stark conditions afforded imine 6 , which was trapped with trichloroacetyl chloride to give enamide 7 . The trichloroacetamide was treated with Bu 3 SnH/AIBN (syringe pump addition) in refluxing benzene to give the 5- endo - trig cyclization product, hydroindole 4 , containing the all-carbon quaternary center, in 77% yield (10 g scale). , The success of this cyclization from a trichloroacetamide is due to the electrophilicity of the carbamoyldichloromethyl radical and a relatively low energy barrier for the rotation around both the NCO amide and N -alkenyl bonds. Enamide 4 was allylated using LHMDS and allyl bromide at −78 °C to diastereoselectively afford 8 in near-quantitative yield.…”

Nucleophilic Aliphatic Substitution

“…42 The reactions, which occur with a high de regiospecificity and stereoselectivity, give only or predominately (31) with the nucleophile cis to the OH group generated from the 10-oxa oxygen in the ring-opening reaction. A possible mechanism is shown in Scheme 14 for reactions using alcohols, amines, and phenylboronic acid as the nucleophile.…”

“…62 The results also suggest that the failure of theoretical calculations to reproduce the experimental KIEs in DMSO was not due to a lack of solvent modeling in the calculations. 63 The large, inverse, solvent kinetic isotope effects, k CH 3 OD/ k CD 3 OD = 0.84 and k CH 3 OH/ k CD 3 OH = 0.74 found in the reaction (Scheme 20) of methanol with the intermediate aziridine (44) produced in the reaction between tetramethylethylene (43) and N -phenyltriazolinedione (42), 64 supported the existence of a tight S N 2-type transition state (45) with extensive O-C bond formation in the ring-opening step of the reaction, i.e. these KIEs were attributed to the lesser steric hindrance with the smaller deuterated solvent.…”