Copper enantioselective reactions

Jorgensen has recently reported similar enantioselective reactions between N-tosylimines 107 and trimethylsilyldiazomethane (TMSD) catalyzed by chiral Lewis acid complexes (Scheme 1.32) [57, 53]. The cis-aziridine could be obtained in 72% ee with use of a BINAP-copper(i) catalyst, but when a bisoxazoline-copper(i) complex was used the corresponding trans isomer was fonned in 69% ee but with very poor diastereoselectivity. 

The use of vinyl epoxides as substrates in enantioselective copper-catalyzed reactions, on the other hand, has met with more success. An interesting chiral ligand effect on Cu(OTf)2-catalyzed reactions between cyclic vinyloxiranes and dialkylzinc reagents was noted by Feringa et al. [51]. The 2,2 -binaphthyl phosphorus amidite ligands 32 and 43 (Fig. 8.5), which have been successfully used in copper-catalyzed enantioselective conjugate additions to enones [37], allowed kinetic resolution of racemic cyclic vinyloxiranes (Scheme 8.26). 

Likewise, PEG-supported bisoxazoline (40) can be used as a ligand for copper-mediated enantioselective reactions such as cyclopropanations of alkenes, [2-1-4] cycloadditions as well as ene reactions. Best results were obtained in case of the latter reactions as products were formed in yields up to 96% and ee s up to 95% (Scheme 4.25) [117]. 

A copper-catalyzed reaction using a chiral diphosphine hgand, DuPHOS, with an added lanthanide salt, provides good levels of enantioselectivity (67-91% ee) in additions of the simple allylboronate 31 to both aromatic and aliphatic ketones that present a large difference of steric bulk on the two sides of the carbonyl group. One such example is shown in Eq. 81. On the basis of B NMR experiments and on the lack of diastereoselectivity in crotylation reactions, the... 

Kobayashi earlier demonstrated the first use of enamides and enecarbamates as nucleophiles in several enantioselective copper-catlayzed reactions [30]. Inspired by this precedent, Terada reported that 0.1mol% of Im effectively... 

Copper complexes catalyze formally related aziridination of olefins with ]7V-(p-toluenesulfonyl)imino]phenyliodinane, a nitrene precursor (219b). As exemplified in Scheme 98, catalysts formed from Cu(I) tri-flate and optically active bis(oxazolines) effect enantioselective reaction of styrene (Scheme 98) (218b, 219a). 

Enantioselective allylation, via indium compounds, 9, 672 Enantioselective conjugate additions, in C-G bond formation copper nucleophiles, 10, 373 lithium nucleophiles, 10, 370 magnesium nucleophiles, 10, 371 zinc nucleophiles, 10, 374 Enantioselective reactions... 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

A copper-catalysed, enantioselective, conjugate addition of a terminal alkyne, which undergoes an in situ metallation, has been reported. The addition of phenylacetylene to Meldrum s acid-derived acceptors (196) takes place in aqueous medium, without recourse to an inert atmosphere. The success of the enantioselective reaction was made possible by the use of PINAP (198), a new class of P,IV-ligands (cf. QUINAP), which have the advantage of easier resolution. Furthermore, these modular ligands are responsive to numerous electronic and steric modifications that permit optimization of the reaction. The products (197) were obtained in good yields and with 82-97% ee.235... 

Many of the copper-mediated transformations summarized in the previous sections of this chapter can also be performed efficiently with catalytic amounts of copper salts or reagents. Indeed, some of the copper-catalyzed reactions have been discovered before the development of stoichiometric organocopper reagents. The focus of the last decade has been put on new copper-catalyzed transformations (e.g., conjugate reductions) and in particular on the discovery of chiral copper catalysts for highly enantioselective 1,4-addition and S -substitution reactions of prochiral substrates. 

Recently, this unique characteristic of vinylic tellurides was explored in the enantioselective synthesis of macro-lactin A 205, an antiviral macrolactone extracted from sea bacteria. The first step of the synthesis featured the chiral epoxide 203 opening by the vinyl cyanocuprate 202, derived from a tellurium-copper exchange reaction using the vinylic telluride 201, obtained by hydrotelluration of 200 (Scheme 111). Further manipulation of 204 led to macrolactin A 205.271... 

Copper Lewis acids have found many applications in the last decade in a variety of organic transformations and more notably in enantioselective reactions. In particular, Cu(OTf)2 and Cu(SbFg)2 in conjunction with chiral bisoxazolines are the chiral Lewis acids of choice for cycloadditions, aldol reactions, ene reactions, and other selective transformations. Moderately Lewis acidic copper salts are also reagents for transesterifications, dehydrations, and hydrolysis. The thiophilic nature of copper makes them ideal for selective deprotection of thio acetals and thioesters and offer practical advantages over mercury salts. 

Jonasson, C., Roenn, M., Baeckvall, J.-E. An Enantioselective Route to Paeonilactone A via Palladium- and Copper-Catalyzed Reactions. 

Since the bisphosphine as well as a monophosphine greatly accelerate the copper-catalyzed reaction [59], a survey of the known diphosphine was carried out to find that 0.5% of copper(II) triflate and 0.5% of phosphine are sufficient, though enantioselectivity was at most 44% [60]. Chiral phosphite ligand bearing tartrate moiety 28 accelerated the reaction [61], but the ee was not so satisfactory at 40% (Eq. (12.30)) [62]. Chiral thiazolidinone 29 was developed as a chiral ligand to afford the product in 63% ee [63]. 

Similarly, ra 5-cyclopropanes were obtained from alkenes, such as styrene and 2,5-dimethyl-hexa-2,4-diene, with relative yields > 90% when a diazoacetate bearing a bulky ester group was decomposed by a copper catalyst with bulky salicylaldimato ligands. Several metal complexes with bulky Cj-symmetrlc chiral chelating ligands are also suitable for this purpose, e.g. (metal/ligand type) copper/bis(4,5-dihydro-l,3-oxazol-2-yl)methane copper/ethyl-enediamine ruthenium(II)/l,6-bis(4,5-dihydro-l, 3-oxazol-2-yl)pyridine cobalt(III)/ salen. The same catalysts are also suited for enantioselective reactions vide infra). For the anti selectivity obtained with an osmium-porphyrin complex, see Section 1.2.1.2.4.2.6.3.1. 

Kobayashi and coworkers pioneered the use of enamides or enecarbamates as nucleophiles in enantioselective reactions with either glyoxylates or glyoxylate derived imines catalyzed by chiral copper complexes [65]. The reaction using enamides or enecarbamates as nucleophilic components, namely, the aza ene reaction, with imines provides P amino imines that can be readily transformed into... 

Mechanistic studies of rhodium porphyrins as cyclopropanation catalysts have resulted in the spectroscopic identification of several potential intermediates in the reaction of ethyl diazoacetate with olefins, including a diazoniumfethoxy-carbonyl)methyl-rhodium complex formed by electrophilic addition of the rhodium center to the a-C atom of ethyl diazoacetate [29]. It is not known if analogous intermediates are also formed in analogous reactions of copper catalysts. However, the initial part of the catalytic cycle leading to the metal carbene intermediate is not of primary concern for the enantioselective reactions described herein. It is the second part, the reaction of the metal-carbene complex with the substrate, that is the enantioselective step. 

Enantioselective C-H insertion is clearly the domain of chiral dinuclear rhodium catalysts (see Chap. 16.2). Only very few examples of enantioselective copper-catalyzed reactions of this type have been reported. As a possible approach to the mitomycine ring system, Sulikowski has studied the cyclization of diazo esters 28 quite extensively using various chiral transition metal catalysts... 

The cyclisation of nitrones derived from tryptamines is a similar process and can be carried out enanti-oselectively using a chiral Lewis acid."° A similar enantioselective intermolecular process is the copper-catalysed reaction of indoles with tosyl-imines of aromatic aldehydes. "... 

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