A Stereoselective and Regioselective Synthesis of trans,trans-Configured 1,2,3-Trisubstituted Indanes: Cycloaddition of Alkenes with Iodonium Ylides of β-Disulfones

Abstract

S y n t h e s i s o f t r a n s , t r a n s -C o n f i g u r e d 1 , 2 , 3 -T r i s u b s t i t u t e d I n d a n e s Abstract: The reaction of phenyliodonium-bis(sulfonyl) methylides a-g with alkenes 1 affords the multiply trisubstituted indanes 2 in moderate to good yields, through an unusual cycloaddition. The present stereoselective and regioselective cycloaddition provides a convenient preparative route to trans,trans-configured 1,2,3-trisubstituted indanes, in which the benzene ring derives from the arenesulfonyl functionality of the bis(sulfonyl)iodonium ylide. The mechanistically puzzling structural feature is the fact (X-ray structure) that the para-methyl substituent of the original p-toluenesulfonyl group in the iodonium ylide is located in the C-6 position of the resulting indane benzene ring, that is, a meta relationship with respect to the original methylide carbon atom.

The Reaction of PhenyliodoniumBis(phenylsulfonyl)methylide with Alkyl Iodides

“…The exo-conformation of the C-2, C-3 substituents results from the absence (COSY) of a coupling between H-2 and H-3 with the adjacent bridgehead protons. 18 In accord with our previous proposal [11][12][13] and the current results, we offer the mechanism in Scheme 4 to rationalize the formation of the adduct 7. The reaction is presumably initiated by the fast reaction of iodonium ylide 1 with methyl iodide to afford the unstable alkyliodonium ylide 5a.…”

[3+2] Cycloaddition of Phenyliodonium Bis(arylsulfonyl)methylides with α,β-Enones

“…In contrast, if the iodonium bis(sulfonyl)methylide should react initially as an electrophile by attacking the a-ethylenic carbon atom of the a,b-enone, indane derivatives should be formed by [3+2] cycloaddition, as observed for the simple alkenes. 3,4 Indeed, we report here that the reaction of iodonium bis(sulfonyl)methylides 1 with a variety of a,b-enones affords, in moderate yields, 1,2,3-trisubstituted indanes 4 with the trans,trans configuration. Given that the sulfonyl substituent may be reductively cleaved or appropriately modified through established 8 carbanion methodology, the present cycloaddition constitutes a potentially valuable synthetic method for the construction of 2-aroylindane derivatives.…”

“…In contrast, if the iodonium bis(sulfonyl)methylide should react initially as an electrophile by attacking the a-ethylenic carbon atom of the a,b-enone, indane derivatives should be formed by [3+2] cycloaddition, as observed for the simple alkenes. 3,4 Scheme 1 Cycloaddition modes for a phenyliodonium bis(arylsulfonyl)methylide with alkenes r.t. Ph SO 2 Ph Ph (PhSO 2 ) 2 C IPh 1 a PhCH=CHPh H H SO 2 Ph hν or ∆, Cu(acac) 2 P(OEt) 3 PhO 2 S SO 2 Ph (PhSO 2 ) 2 C P(OEt) 3 PhI Downloaded by: University of Florida. Copyrighted material.…”

“…At room temperature, however, an unusual [3+2] cycloaddition occurs, in which a 1,2,3-trisubstituted indane is produced. For example, various acyclic 1,2-disubstituted alkenes, either Z-or E-configured, lead to the trans,trans-indane cycloadducts, 3 whereas cyclic alkenes yield the cis,cisstereoisomers 4 (Scheme 1). This reactivity is explained by postulating an initial electrophilic attack of the ylide on to the alkenyl double bond, followed by cyclization to the [3+2] cycloadduct.…”

Iodonium ylides in organic synthesis

“…Rh(II)-or Cu(II)-catalyzed generation/rearrangement of onium ylides of allyl and benzyl ethers via iodonium ylides; 82 and Rh(II)-or Cu(II)-catalyzed stereoselective cycloaddition of disulfonyl iodonium ylides with alkenes leading to 1,2,3-trisubstituted benzocyclopentenes 83 or functionalized indanes. [84][85][86] Moriarty and co-workers have investigated the intramolecular cyclopropanation of iodonium ylides to the tricyclic ketones in the presence of copper(I) chloride and also in the absence of conventional metal calalysts. 87 Synthetic utility of this methodology has been demonstrated by conversion of ylide 46 to a mixture of diastereomeric products 47 and 48 related to prostaglandins and vitamin D, respectively (Scheme 14).…”