Copper-catalyzed asymmetric

The axially chiral natural product mastigophorene A (70) was synthesized via a copper-catalyzed asymmetric homocoupling of bromooxazoline 68. Treatment of 68 with activated copper in DMF afforded 69 in 85% yield as a 3 1 mixture of atropisomers. The major atropisomer was converted into mastigophorene A (70) the minor regioisomer was transformed into the atropisomeric natural product mastigophorene... 

Tlie constrLiction of carbocydic cotnpoutidi by ring-annulation procedures frequently plays a prominent role in total syntliesis. Tlie tolerance of various functional groups in tlie zinc reagents employed in copper-catalyzed asymmetric 1,4-additions fornis tlie basis for tliree novd catalytic enantioselective annulation metliods discussed bete. 

Copper-catalyzed asymmetric suhstituhon reactions can he classified into three major types ... 

In 1995, aziridination with 1,3-dienes 10 by treatment with PhI=NTs 9 was developed (Scheme 2.4) [10] on the foundation of pioneering works by Jacobsen and Evans on copper-catalyzed asymmetric aziridination of isolated alkenes [11]. 

Other types of new AT-containing ligands have been described as effective chiral inductors for copper-catalyzed asymmetric cyclopropanation. Hence, Fu and Lo [42] prepared a new planar-chiral hgand, namely the C2-symmetric bisazaferrocene (structure 34 in Scheme 18), which was fbimd to be efficient for the cyclopropanation of various olefins with large diastereomeric excesses and ee values up to 95%. 

Copper-catalyzed Asymmetric Allylic Alkylations with Alkylzinc Reagents 403... 

Scheme 6.97 Copper-catalyzed asymmetric allylic oxidation of bridged bicyclic alkenes.

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

The development of this reaction over the subsequent 50 years placed it, along with the Rh(II) variant, as the method of choice for the catalytic cyclopropanation of alkenes. A number of reviews have recently appeared detailing the advances in cyclopropanation (5-10). This reaction remains one of the most recognizable copper-catalyzed asymmetric transformations as evidenced by the plethora of publications utilizing it as a testing ground for new ligands. 

The use of TADDOL-based ligands offers an important alternative for copper-catalyzed asymmetric 1,4-additions. TADDOLs (a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol compounds), introduced by Seebach, are among the most successful currently known ligands in asymmetric catalysis. Seebach also developed the first copper-catalyzed 1,4-addition of a Grignard reagent using a TADDOL derivative as a chiral ligand (see Scheme 7.2) [17]. We have reported TADDOL-based... 

Acyclic Enones as Substrates Compared to cyclic enones, acyclic enones are generally more challenging substrates for the copper-catalyzed asymmetric 1,4-addition reactions. Several ligands have been reported that can achieve high ee when p-aryl acyclic enones are used as substrates in the 1,4-addition of diethyl-zinc (Figure 3.5). ° ... 

However, very few catalyst systems reported to date are highly effective for both p- aryl and p-alkyl acyclic enone substrates in the copper-catalyzed asymmetric 1,4-addition. Ligand 27, developed by Hoveyda, shows high enantioselectivity in the 1,4-addition of dialkylzinc reagents to various acyclic enones (Figure 3.6). " ... 

Nitroalkenes have also been employed in the copper-catalyzed asymmetric... 

Ligand 4, which is highly effective for the 1,4-addition of diethylzinc to 2-cyclohexen-l-one, shows relatively wide scope with respect to the p-substituent in the copper-catalyzed asymmetric 1,4-addition of diethylzinc to acyclic nitroalkenes... 

As recent examples of copper-catalyzed asymmetric conjugate addition of organo-zinc reagents (a) Mizutani, H. ... 

SCHEME 16. Copper-catalyzed asymmetric synthesis of chiral aUyhc esters synthesis of a natural butenoUde using aUyUc alkylation foUowed by ring-closing metathesis... 

For recent reviews on copper-catalyzed asymmetric aUyhc substitution, see ... 

Soai [8], Bolm [9], Feringa [10], and Alexakis [11] have reported nickel-or copper-catalyzed asymmetric conjugate addition of diethylzinc, with chiral amino alcohols or a chiral trivalent phosphorus compound (Scheme 8D.2). 

A parallel development during this period was the identification of chiral bis(oxazolines) and bis(benzylidene)diaminocyclohexanes as useful ligands for copper-catalyzed, asymmetric tosylaziridination reactions with Phi = NTs (Scheme 64) [174,175]. Evidence for the likely formation of copper(III)-nitrene intermediates,cCu(III) = NTs , in such reactions was also reported [176]. 

A new class of phosphaferrocene-oxazoline ligands has been disclosed by Fu and co-workers30 and applied to the copper-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones with good enantioselectivity. The substitution pattern on the phosphoryl ring as well as on the oxazoline was shown to have an enormous impact on the selectivity. Ligands 26 and 27, which share the same absolute configuration in the oxazoline, provide the (5)-l,4-adduct preferentially. This observation led to the conclusion that the stereochemistry at the oxazoline, and not the planar... 

Hawner C, Li K, Cirriez V, Alexakis A (2008) Copper-catalyzed asymmetric conjugate addition of aryl aluminum reagents to trisubstituted enones construction of aryl-substituted quaternary centers. Angew Chem Int Ed 47 8211-8214... 

The coordination of NHC ligands greatly enhances the copper-catalyzed asymmetric addition of diethylzinc to cyclohexenone [45]. Employing imi-dazolinylidene ligands with chiral centers in the heterocycle, the alkylation of a-enones [46,47] was systematically studied by the groups of Mangeney and Alexakis [10,48-50]. A summary of the results obtained is presented in Table 1. 

The first versatile system for the copper-catalyzed asymmetric coupling of alkynes with nitrones to form c/.v-p-lactarns has been developed using a bis(azaferrocene) ligand <02JACS4572>. 

Copper-catalyzed asymmetric allylic alkylations with organometalUc reagents used for small-ring openings, such as epoxides and aziridines, have gained interest. Illustrating... 

Asymmetric Copper-Catalyzed Cyclopropanation. Since the pioneering work of Nozaki and his co-workers, several chiral ligands have been designed to achieve high enantio and diastereoselectivity in copper-catalyzed asymmetric cyclopropanation of olefins. Masamune introduced C2-symmetric bisoxa-... 

Like BINOL, salicylaldehyde imines have become very important in asymmetric catalysis and a variety of polydentate ligands prepared from chiral monoamines and diamines are employed in oxidation reactions, carbenoid reactions and Lewis acid catalyzed reactions. As in the previous section, this section emphasizes the effect of the phenol moiety on the asymmetric catalysis. An imine derived from a chiral 1-phenethylamine and salicylaldehyde was employed in the copper catalyzed asymmetric cyclopropanation by Nozaki, Noyori and coworkers in 1966, which is the first example of the asymmetric catalysis in a homogeneous system . Salicylaldehyde imines with ethylenediamine (salen) have been studied extensively by Jacobsen and Katsuki and their coworkers since 1990 in asymmetric catalysis. Jacobsen and coworkers employed the ligands prepared from chiral 1,2-diamines and Katsuki and coworkers sophisticated ligands possess chirality not only at the diamine moiety but also at the 3,3 -positions. 

Aryl-5,5-bis(oxazolin-2-yl)-l,3-dioxanes 169 have been easily prepared in three steps from diethyl bis(hydroxymethyl)malonate, amino alcohols, and aromatic aldehydes. They have been used for the copper-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate in up to 99% ee for the trawx-cyclopropane (maximum transicis ratio = 77/23) <05TA1415>. The same reaction performed on 2,5-dimethyl-2,4-hexadiene with tert-butyl diazoacetate in the presence of copper catalysts bearing ligand 170, prepared from arylglycines, exhibited remarkable enhancement of the rrawx-selectivity (transicis ratio = 87/13), with 96% ee for the trans product <05JOC3292>. 

Given the significant existing knowledge-base in asymmetric catalytic cyclo-propanation (Chap. 16), the discovery that metal ions useful for catalysis of carbene transfer to alkenes were also effective for nitrene transfer to the same substrates opened a clear new direction for research in asymmetric aziridination. Brief mention of the asymmetric catalysis of the aziridination of styrene was made in two early reports on (bisoxazoline)copper-catalyzed asymmetric cyclopropanations [20,21], and subsequently new methods for copper-catalyzed asymmetric aziridination were revealed in two independent studies published simultaneously by Jacobsen and Evans [22,23]. 

Copper-Catalyzed Asymmetric Baeyer-Villiger Oxidation. ... 

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