Using epoxy enol triethylsilanes as oxyallyl cation precursors, [4 + 3] cycloadditions with various dienes occur under catalysis by silyl triflates and acids in good yields. The intramolecular [4 + 3] cycloaddition proceeds under mild conditions and generate hydroxylated cycloadducts with high diastereoselectivity and yields. Enantiomerically pure epoxy enol silanes have been shown to give excellent yields of the optically pure cycloadduct bearing multiple stereocenters.
Silyl triflate-catalyzed (4+3) cycloadditions of epoxy enolsilanes with dienes provide a mild and chemoselective synthetic route to seven-membered carbocycles. Epoxy enolsilanes containing a terminal enolsilane and a single stereocentre undergo cycloaddition with almost complete conservation of enantiomeric purity, a finding that argues against the involvement of oxyallyl cation intermediates that have been previously proposed for these types of reactions. We report theoretical and experimental investigations of the cycloaddition mechanism. The major enantiomer of cycloadduct is derived from an SN2-like reaction of the silylated epoxide with the diene, in which stereospecific ring opening and formation of the two new C–C bonds occur in a single step. Calculations predict, and experiments confirm, that the observed small losses of enantiomeric purity are traced to a triflate-mediated double-SN2 cycloaddition pathway.
The (4+3) cycloaddition reaction is a direct and efficient method to construct seven-membered carbocycles. [1] Isoelectronic with the Diels-Alder reaction, the classical mechanistic understanding of this reaction is that an allyl cation dienophile, contributing two electrons, undergoes cycloaddition with the diene (Scheme 1). Cyclic dienes are commonly employed, thus resulting in bicyclic adducts which are useful synthetic intermediates. [2] Compared with the (4+2) reaction, however, asymmetric (4+3) cycloadditions remain underdeveloped. [3] Other than two examples of asymmetric catalysis, [4] the majority of asymmetric versions of (4+3) cycloadditions rely on chiral auxiliaries or incorporate chiral elements into the reacting cation or the diene. [5,6] On the basis of the seminal work by Eguchi et al., [7] we have developed a silyl-triflate-catalyzed intramolecular (4+3) cycloaddition reaction of furan-tethered epoxy enolsilanes such as 1, and it affords the cycloadduct 2 in excellent yield and diastereoselectivity (Scheme 2). [8] The corresponding intermolecular (4+3) cycloadditions with epoxy enolsilanes such as 3 a have also been observed to generate endo and exo cycloadducts with facial selectivity (Scheme 2). [9] In both cases, the reactions with optically active epoxy enolsilanes generate cycloadducts with high conservation of the enantiomeric excess. [8,10] Each of these cycloadducts has inherited one stereocenter (* in Scheme 2) from the epoxide precursor, so the observed selectivity could be understood as a diastereoselective cycloaddition of chiral oxyallyl cations, similar to the previously reported asymmetric (4+3) cycloadditions involving chiral cations. [5] In contrast, for intermolecular (4+3) cycloadditions of simpler enolsilanes such as the optically pure 5 a (Scheme 3), the corresponding oxyallyl cation would be expected to be devoid of any stereochemical elements, and should engender racemic cycloadducts. However, we have observed that the enantiomeric purity was, in fact, highly conserved in the cycloaddition. The treatment of 5 a, having a 99 % ee, with a catalytic amount of TESOTf in the presence of furan and a subsequent Et 3 N·3 HF desilylative workup resulted in endo and exo diastereomers with 92 and 97 % ee, respectively. [11] Cycloaddition with the more reactive cyclopentadiene afforded products with even higher enantiomeric excesses, thus showing essentially a complete retention of chirality.The absolute stereochemistry of the cycloadducts a-6 a and b-6 a were determined by X-ray crystallographic analysis of their (À)-camphanoyl and p-bromobenzoyl ester derivatives, 7 a and 7 b, respectively (see the Supporting Information for structures). [12] The observed absolute stereochemistry implies that carbon-carbon bond formation occurred with inversion of stereochemistry at the epoxide. The high degree of enantiomeric excess observed in this (4+3) cycloaddition shows that the reaction did not proceed through the putative achiral oxyallyl cation intermediate, which would necessitate that mos...
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