A-chiral Lewis acid complexes

For the enantioselective synthesis of chiral chromanes such as 2-213, a chiral Lewis acid complex, formed in situ from Mg(OTf)2 and 2-212, is assumed to catalyze the domino transformation of the phenols 2-210 and the p,y-unsalurated a-ke-toesters 2-211 (Scheme 2.50). 2-213 was obtained in excellent diastereoselectivity, but only in mediocre enantioselectivity. 

The most common sources of the chiral ligands employed for making a chiral Lewis acid complex are chiral diols with a C2-symmetric axis. This C2-symmetric feature reduces the number of competing transition states, which is... 

Mukaiyama and co-workers developed a chiral Lewis acid complex 15 consisting of tin (II) triflate and a chiral diamine. An aldol reaction of enol silyl ether 16 and octanal is promoted by 15 to give 17 in a highly diastereo-and enantioselective manner. The enantioface of the aldehyde is selectively activated by coordination with 15. This method is similar to method 3, in that an aldehyde-chiral Lewis acid complex can be regarded as a chiral electrophile. An advantage of method 4 over method 3 is the possible catalytic use of a chiral Lewis acid. In the reaction of Scheme 3.6, 20 mol% of 15 effects the aldol reaction in 76% yield with excellent selectivity.9... 

Sibi et al. [66] reported the first examples of highly enantioselective conjugate amine additions [67] by use of catalytic amounts of a chiral Lewis acid complex. Addition of 0-benzylhydroxyamine 87 (1.1 equiv.) to the pyrazole-derived crotonamide 86 proceeded smoothly in the presence of stoichiometric amounts of the chiral catalyst prepared from the bis(oxazoline) 50 and MgBr2 OEt2 with high enantiomeric excess (96 % ee) (Sch. 37). This conjugate addition reaction was equally effective with catalytic amounts of the chiral Lewis acid (92 % ee with 30 mol % 88 % ee with 10 mol %). A re face amine addition to the s-cis substrate bound to the chiral complex with tetrahedral- or ds-octahedral arrangements XXXII and XXXni accounts for the product stereochemistry observed (Fig. 7). 

In instances where a chiral Lewis acid complex is used in order to impart stereocontrol, several issues are at hand ... 

In 2004, Nishiyama and Iwasa reported that a chiral Lewis acid complex, generated from Mn(C104)2 and the chiral xabox ligand 12, could be used as an efficient catalyst for the asymmetric 1,3-DC reactions of nitrones 9 with 3-alkenoyl oxazolidinone 10 [12]. These reactions were typically carried out at room temperature and provided the corresponding isoxazolidines 11 in good to excellent stereoselectivities (Scheme 2.5). 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

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. 

High levels of asymmetric induction (97-74% ee) along with high diastereoselectivity (>99 1-64 36) were reported for asymmetric 1,3-dipolar cycloaddition reactions of fused azomethine imines 315 and 3-acryloyl-2-oxazolidinone 709 leading to 711 using a chiral BINIM-Ni(n) complex 710 as a chiral Lewis acid catalyst (Equation 100) <20070L97>. 

A lead(II) triflate-crown ether complex functions as a chiral Lewis-acid catalyst for asymmetric aldol reactions in aqueous media (Scheme 86).352 This is the first example of a chiral crown-based Lewis acid that can be successfully used in catalytic asymmetric reactions. 

Complex (J )-140 serves as a chiral Lewis acid and coordinates to the aldehyde at the less hindered /J-face of 141. i e-side cyanation of (J )-141 and the subsequent cleavage of the alkoxide group give the product 142. Because at this stage the catalyst turnover is blocked, the reaction cannot be carried out in a catalytic manner. 

It should be noted that asymmetric acyl transfer can also be catalyzed by chiral nucleophilic A-heterocyclic carbenes [27-32] and by certain chiral Lewis acid complexes [33-37] but these methods are outside the scope of this review. Additionally, although Type I and Type II tr-face selective acyl transfer processes have been reported to be catalyzed by some of the catalysts described in this review, these also lie outside the scope of this review. 

This modification is based on the consideration that such bidentate dienophiles would form rigid complexes with a chiral Lewis acid, resulting in high reactivity and a good level of TT-facial selectivity during the cycloaddition reaction. 

The asymmetric fluorination of enolates by means of chiral metal complexes has been reported with Selectfluor in the presence of a chiral Lewis acid derived from TADDOL (TiCl2/TADDOL), or with F-A-sulfonimide (NFSI) with palladium complexes and chiral phosphines. 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Figure 8B1.2. Proposed structure for a chiral Lewis acid-aldehyde complex.

A chiral Lewis acid-catalysed method for the 1,2-migration of (dichloromethyl)borate complexes to provide synthetically useful (a-chloroalkyl)boronates has been developed,557 and the diastereoselective rearrangement of the a,a-dichloromethylboronate derivatives of 1,2-diols, (427) —> (429), has been explained558 on the basis of a bidentate interaction between the catalytic Lewis acid and the substrate, leading to a favoured transition state (428). 

Nitro compounds are also useful starting materials, because a nitro group can be readily converted to a carbonyl group or to amino functionality. Addition reactions of nitroalkane have been reported by Yamaguchi [13b], Shibasald [6a], Bako and Toke, Corey, Hanessian, and Kanemasa [21]. For example, Kanemasa used their chiral Lewis acid complex 35 for the reaction of 36 with nitromethane (Scheme 18). The reaction proceeded with the aid of the amine co-catalyst, affording the product 37 with high enantioselectivity. This system was also applicable to the reaction of malononitrile [2 le]. 

The choice of solvent has had little, if any, influence on the majority of Diels-Alder reactions.210,211 Although the addition of a Lewis acid might be expected to show more solvent dependence, generally there appears to be little effect on asymmetric induction.118129 However, a dramatic effect of solvent polarity has been observed for chiral metallocene triflate complexes.212 The use of polar solvents, such as nitromethane and nitropropane, leads to a significant improvement in the catalytic properties of a copper Lewis acid complex in the hetero Diels-Alder reaction of glyoxylate esters with dienes.213... 

Substituted benzoxazol-2(3//)-ones behaved as achiral templates for enantioselective DA reactions as a result of a chiralrelay effectofthe substituent atC-4position. Upon complexation with a chiral Lewis acid, iV-acryloylbenzoxazol-2(3//)-ones should take up the two distereomeric conformations 153a and 153b because of the presence of a chiral axis in the substrate. The best results were obtained with benzyl derivatives. <02OL39>. 

Achari B, Mandal SB, Dutta PK, Chowdhury C (2004) Synlett 2004 2449 Aggarwal VK, Belfield AJ (2003) Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes. Org Lett 5 5075-5078 Akiyama T, Itoh J, Fuchibe K (2006c) Adv Synth Catal 348 999 Akiyama T, Itoh J, Yokota K, Fuchibe K (2004) Enantioselective Mannich-type reaction catalyzed by a chiral Brpnsted acid. Angew Chem Int Ed Engl 43 1566-1568... 

Kobayashi and co-workers. used zirconium-based bromo-BINOL complex for the catalytic enantioselective Mannich-type reaction. The o-hydroxyphenyl imine 3.36 chelates the Zr(IV)(BrBINOL)2 to form the activated chiral Lewis acid complex A. The ketone acetal 3.37 reacts with the Lewis acid complex A to give the complex B. The silyl group is then transferred to the 3-amino ester to form the product 3.38 and the catalyst Zr(BrBINOL)2 is regenerated, which is ready for binding with another imine molecule (Scheme 3.16). 

R,R)-4,6-Dibenzofiirandiyl-2,2 -bis(4-phenyloxazoline), DBFOX/Ph (5), is a novel tridentate bisoxazoline ligand developed by Kanemasa and coworkers that has been successfully used as a chiral Lewis acid in enantioselective Diels-Alder-reactions, nitrone cycloadditions and conjugate additions of radicals and thiols to 3-(2-alkenoyl)-2-oxazolidinones. Representative examples for cycloadditions using the Ni(C104)2-6H20 derived complex are shown below. 

The first asymmetric ene reaction catalyzed by a chiral Lewis acid appeared in a report by Maruoka, Hoshino, Shirasaka, and Yamamoto in 1988 and utilized the aluminum complex 98 [61]. The presence of the triphenylsilyl groups on the 3 and 3 positions of the catalyst was crucial—it was found that the diphenyl analog 302 gave racemic product 301 from the reaction of chloral with 2-thiophenylpropene whereas catalyst 98 gave 301 in 57 % ee (Sch. 37). 

Most organic free radicals are nucleophilic and will react with electrophilic centers. Lewis acids have been used to activate aj3-unsaturated carbonyl compounds towards addition of free radicals and also to stabilize a-keto radicals [67]. The first report of the use of a chiral Lewis acid to effect an asymmetric free-radical reaction was that of Urabe, Yamashita, Suzuki, Kobayashi, and Sato in 1995 [68]. They found that if the BINOL aluminum catalyst 313 is stoichiometrically complexed with lactone 323 and then treated with butyl iodide and tributylstannane in the presence of triethylborane the alkylated lactone 324 can be isolated in 47 % yield with 23 % ee (Sch. 40). 

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