Lewis acids copper acetate

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. 

For the Cu(OTf)2-promoted reaction between ethyl diazoacetate and cinnam-aldehyde dimethyl acetal, products 143-145 account for only 35% the total yield. C/C and C/H insertion products 151 and 152 are obtained additionally in 49 and 14% yield, respectively154). It was assumed that the copper compound acts through Lewis-acid catalysis here, just as it is believed to do when orthoesters are used as substrates 160). According to this, catalyst-induced formation of a methoxy-... 

Copper-based Lewis acids can be applied to various kinds of reaction. While Cu1 complexes catalyze acetal formation (Scheme 44), Cu(OTf)2 is used for formation of glycosyl bonds. 86,187 Since the ability of Cu(OTf)2 to be chelated by the substrate is essential for the reaction, typical Lewis acids such as BF3-OEt2 and Me3SiOTf are ineffective. 

Copper-based Lewis acids have some advantages for hydrolysis reactions they are mild, nonacidic, and can control reactions due to chelation by the substrate to achieve high selectivity. CuS04 is effective for acetal deprotection (Scheme 47).197 Thioacetals198,199 and selenoacetals200-202 are also hydrolyzed by copper Lewis acids, and dehydration is accelerated by Cu11 Lewis acids under mild conditions.203... 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

Takaya and co-workers (256) disclosed that chiral copper alkoxide complexes catalyze the transesterification and kinetic resolution of chiral acetate esters. Selec-tivities are very poor (E values of 1.1-1.5) but it was noted that the Lewis acid BINAP CuOTf was not an effective catalyst. The observation thatp-chlorophcnyl-BINAP-CuOf-Bu complex gave faster rates than BINAP-CuOt-Bu suggests that both the Lewis acidic and Lewis basic properties of the copper alkoxide are required for optimal reactivity. 

Because of the high nucleophilicity and reactivity of diazoalkanes, catalytic decomposition occurs readily, not only with a wide range of transition metal complexes but also with Brpnsted or Lewis acids. Well-established catalysts for diazodecomposition include zinc halides [638,639], palladium(II) acetate [640-642], rhodium(II) carboxylates [626,643] and copper(I) triflate [636]. Copper(II)... 

Except for the well-documented conjugate additions of diethylaluminum cyanide,92 triethylaluminum-hydrogen cyanide and Lewis acid-tertiary alkyl isonitriles,93 examples of Lewis acid catalyzed conjugate additions of acyl anion equivalents are scant Notable examples are additions of copper aldimines (233),94, 94b prepared from (232), and silyl ketene acetals (234)940 to a,(3-enones which afford 1,4-ketoal-dehydes (235) and 2,5-diketo esters (236), respectively (Scheme 37). The acetal (234) is considered a glyoxylate ester anion equivalent. 

The imines 12 (X = 4-CH3-QH4-SO2 (Ts), Ar, C02R, COR, etc.) preformed or generated in situ from N,0- or N,N-acetals or hemiacetals are another important class of Mannich reagents frequently used for diastereo- and/or enantioselective aminoalkylation reactions catalyzed by chiral Lewis acids (usually copper or palladium BINAP complexes such as 13). Among other things excellent results were obtained in the aminoalkylation of silyl enol ethers or ketene acetals [24], A typical example is the synthesis of Mannich bases 14 depicted in Scheme 5 [24b], Because of their comparatively high electrophilicity imines 12 could even be used successfully for the asymmetric aminoalkylation of unactivated alkenes 15 (ene reactions, see Scheme 5) [24h, 25], and the diastereo- and/or enantioselective aminoalkyla-... 

A number of Lewis acidic metal salts have been tested in the acetylation of alcohols with acetic anhydride and acetic acid.[67] Of these, copper(II) triflate showed by far the highest activity, but the recycling potential was low. The recyclability was found to be much better with either Sc(OTf)3 or Yb(OTf)3. The reaction between benzyl alcohol and acetic anhydride proceeded to completion within one hour, whereas with acetic acid two days were required under identical reaction conditions. Of the ionic liquids tested, the best activities were obtained in [C4Ciim][PF6]. 

Lewis acids can also be exploited for the cleavage of isopropylidene derivatives. One of the mildest examples comes from a synthesis of Lankacidin in which cleavage of an isopropylidene acetal without harm to a p-methoxybenzyl ether was effected with copper(Il) chloride dihydrate in methanol at reflux [Scheme 3.11].13 Alternatively, zinc(II) nitrate hexahydrate in acetonitrile at 50 DC can be used in which case even a primary tert-butyldimethylsilyl ether survives [Scheme 3.12].14 During a synthesis of Quinocarin, Katoh and co-workerscleaved an isopropylidene group using iron(IIT) chloride adsorbed onto silica gel [Scheme 3.13]. 

The mild deprotection of acetal 15 with CUSO4 in acetone was accomplished in high yield [12]. The mildness of copper Lewis acids for the hydrolysis of hydra-zones [13] is advantageous for acid-sensitive substrates (Sch. 5). The /3,a-unsaturated hydrazone 17 was effectively hydrolyzed without conjugation of the double bond to afford 18 in good yield (Sch. 5) [14]. SAMP-Hydrazones can be hydrolyzed without racemization [15]. The two-step alkylation and hydrolysis of 19 provided 20 in 84 % overall yield and 94 % ee. 

Another advantage over other Lewis acids is the thiophilic nature of copper this has led to its utility in the hydrolysis of thioacetals. Copper(II) chloride in conjunction with copper(II) oxide was introduced by Mukaiyama [16] for the deprotection of 1,3-dithianes and this method has found utility in a variety of synthetic protocols (Sch. 6) [17]. This combination, in which copper oxide plays the role of a buffer to prevent the medium from becoming too acidic, has also found application in the hydrolysis of a-heteroatom substituted and vinyl sulfides [18]. Acetals, which are prone to epimerization under acid-catalyzed hydrolysis conditions (21), can be con-... 

Copper(I) and (II) Lewis acids affect the alkoxyselenation of olefins (Sch. 18). Thus, cyclohexene affords trans adducts 71 in the presence of PhSeCN and CUCI2 [44]. The Lewis acid enhances the electrophilic nature of the selenium by coordination to the nitrile. The reaction is regioselective as terminal olefins afford primary selenides (alcohol addition to the internal carbon) and vinyl acetates yield (8-seleno-a-alkoxyacetates. 

The decarboxylation of amino acids is facilitated by copper Lewis acids. Treatment of tryptophan with copper(II) acetate in HMPA afforded tryptamine 117 in 45 % yield (Sch. 26) [58]. Chelation is thought to activate the carboxylate for elimination. The stable chelate can be isolated and undergoes decarboxylation when heated. An asymmetric version of a similar decarboxylation of malonate derivatives has been reported poor selectivity resulted from addition of chiral alkaloids [59]. 

The low face-selectivity in the previous example can be partially attributed to single-point coordination of the aldehyde to the Lewis acid. Evans and co-workers have used a-alkoxy aldehydes in aldol reactions with much success (Sch. 35) [70]. Thus a variety of silylketene acetals add to 144 in the presence of a copper(bisoxazoline) catalyst with very high selectivity and chemical yields. Reaction with 147, which contains an additional stereoelement, gave a single aldol product 148 with high syn selectivity. The dienol silane 149 also provides high selectivity in the aldol reaction. A square pyramidal model accounts for the observed selectivity. In this model, the substrate binds... 

Activation of C=N double bonds by copper Lewis acids for nucleophilic addition has also been reported (Sch. 37) [73]. The a-imino ester 157 undergoes alkylation at the imine carbon with a variety of nucleophiles when catalyzed by copper Lewis acids. The presence of the electron-withdrawing ester group increases the reactivity of the imine and also assists in the formation of a stable five-membered chelate with the Lewis acid. Evidence for Cu(I) Lewis-acid catalysis and a tetrahedral chelate was obtained by FTIR spectroscopy, from the crystal structure of the catalyst, and from several control experiments. The authors rule out the intermediacy of a copper enol-ate in these transformations. The asymmetric alkylation of A,0-acetals with enol silanes mediated by a copper Lewis acid proceeding with high selectivity has been reported [74],... 

Acetals prepared from chiral diols and carbonyl compounds serve as a chiral synthetic equivalent of aldehydes or ketones. 1,3-Dioxanes synthesized from chiral 2,4-pentanediols are especially useful, and high asymmetric inductions are observed in the Lewis acid promoted reactions of a variety of organometallic compounds. After the removal of the chiral auxiliary by the oxidation and -elimination procedures, optically active alcohols are obtained. Optically active propargylic alcohols and cyanohydrins are synthesized from organosilane compounds, TMS-C CR or TMS-CN in the presence of TiCU (Scheme 24). 1 6-138 Reactive wganometals such as alkyl-lithiums, -magnesiums or -coppers also react with chiral... 

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