The Enantioselectivity and the Stereochemical Course of Copper-Catalyzed Intramolecular CH Insertions of Phenyliodonium Ylides

Abstract

The Cu-catalyzed intramolecular CH insertion of phenyliodonium ylide 1b was investigated at 08 in the presence of several chiral ligands. Enantioselectivities varied in the range 38 ± 72%, and were higher than those resulting from reaction of the diazo compound 1c at 658. The intramolecular insertion of the enantiomerically pure methyl diazoacetate (R)-20 and of the corresponding phenyliodonium ylide (R)-21 proceeded to (R)-23 with retention of configuration with [Cu(hfa) 2 ] (hfa hexafluoroacetylacetone 1,1,1,5,5,5-hexafluoropentane-2,4-dione) and [Rh 2 (OAc) 4 ]. These results are consistent with a carbenoid mechanism for the Cu-catalyzed insertion with phenyliodonium ylides. However, the insertion of the perfluorosulfonated phenyliodonium ylide (R)-29 afforded with [Cu(hfa) 2 ] as well as with [Rh 2 (OAc) 4 ] the cyclopentanone derivative 30 as a cis/trans mixture with only 56 ± 67% enantiomeric excess.Introduction. ± The decomposition of diazo compounds in the presence of transition metals leads to reactions typical for metal-carbenoid intermediates, such as cyclopropanations, insertions into XÀH bonds, and formation of ylides with heteroatoms having lone pairs available. The Cu-catalyzed asymmetric cyclopropanation is probably the most popular application of the transition-metal-catalyzed carbenoid reactions [1]. In addition, Cu-catalyzed decomposition of diazo compounds may also lead to CH bond insertions, although Rh II catalysts are usually more appropriate for these latter transformations [2]. The Rh II -catalyzed insertion proceeds with retention of configuration at the C-atom undergoing the reaction [3], and all the experimental evidence is consistent with a mechanism involving a rhodium-carbenoid as the reactive intermediate [4]. In contrast, the mechanism of the Cu-catalyzed CH insertion has not been investigated systematically, but is assumed to be analogous to that of the reactions catalyzed by Rh II .Since diazo compounds are potentially explosive, toxic, and cancerogenic [5], the number of their industrial applications is limited [6]. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical [7] [8], thermal [8] [9], and transition-metal-catalyzed [10] decompositions exhibit analogies to that of diazo compounds, and, accordingly, carbene or carbenoid intermediates are usually assumed to be involved in these reactions [9 ± 11] although little effort has been made to demonstrate the involvement of these putative species. Some years ago, we presented evidence for metal-carbenoid pathways in Rh II -catalyzed cyclopropanation and CH insertion reactions [11].The mechanism of the Cu I -catalyzed decomposition of phenyliodonium ylides is controversial. Originally, Hayasi et al. proposed a copper-complexed carbene intermediate in the Cu I -catalyzed decomposition of phenyliodonium ylides derived

Iodonium ylides in organic synthesis

“…A detailed discussion of the reaction mechanisms and synthetic applications of iodonium ylides as carbene precursors can be found in the earlier reviews. [14][15][16][17][18] Bis(methoxycarbonyl)(phenyliodinio)methanide 4, the most common iodonium ylide derived from malonate methyl ester, has found synthetic applications in the C-H insertion reactions, [57][58][59][60][61] and in the cyclopropanation of alkenes, 22,28,[62][63][64][65][66] including enantioselective cyclopropanations in the presence of chiral rhodium complexes. 15,67,68 Representative examples of these reactions are shown in Scheme 12 and include the BF 3 -catalyzed bis(carbonyl)alkylation of 2-alkylthiophenes 43, 58 and the optimized procedure for rhodiumcatalyzed cyclopropanation of styrene 44.…”

“…60,64,73,74,88 For example, the copper(II)-catalyzed intramolecular C-H insertion of phenyliodonium ylide 49 in the presence of chiral ligands followed by hydrolysis and decarboxylation affords product 50 in moderate yield with up to 72% ee (Scheme 15).…”

Asymmetric Synthesis through C–H Activation

“…Traditionally, copper complexes have been used as catalysts for carbenoid reactions, but the high electrophilic character of the intermediate carbenoid complex renders it somewhat too reactive to achieve selective C -H insertions [49,57,73,139,140] . Nevertheless, copper(I) complexes, typically with C 2 -symmetric bidentate ligands, have been reported to give moderately good enantiocontrol in intramolecular C -H insertions of α -diazo -β -ketoesters [73] .…”

“…Nevertheless, copper(I) complexes, typically with C 2 -symmetric bidentate ligands, have been reported to give moderately good enantiocontrol in intramolecular C -H insertions of α -diazo -β -ketoesters [73] . The bisoxazoline class of ligands has achieved the most success [73,128,140 -144] , whereas binaphthyl and salen complexes resulted in low to moderate levels of enantiocontrol [57,72,73,128,145 -147] .…”

Enantioselective C–H carbene insertions with homogeneous and immobilized copper complexes

“…5 The use of these metals in enantioselective carbene insertions is rather scarce and poor results are commonly reported. Copper complexes with chiral bis(oxazolines) and related ligands have been described as catalysts for intramolecular insertions of 30 carbenoids from phenyliodonium ylides 6 or diazocompounds. 7 Those reactions take place with low yields or chemoselectivities, and moderate to low enantiomeric excess, 15-60% e.e.…”