Enantioselective reactions aldol-type additions

The estimation of the conditions, suppressing the silyl-mediated catalysis and preferable for the carbenium-promoting catalysis, is of significant importance to introduce the chiral information in the product. Since it was observed that a carbe-nium salt promoted the reaction and thus provided the enantioselectivity in the outcome, the rigid conformation and the enhanced reactivity of the carbocation may be the key requirement for the productive enantioselective carbenium catalysis in the aldol-type additions. 

Enantioselective Aldol-Type Additions. Highly enantiose-lective aldol-type reactions are successfully carried out by the combined use of a chiral diamine-coordinated tin(II) triflate and trihutyltin fluoride (eq 10). A catalytic amount of chiral his(sulfonamido)zinc(Il), easily prepared from diethylzinc and chiral sulfonamides, promotes the aldol addition in high yield and... 

In 2008, Zhang et al. succeeded in a three-component cascade reaction using achiral Ru and chiral Zr catalysis [14]. Under the influence of achiral Rh(OAc)j, oxonium ylide was generated from diazo compound 37 and alcohol 38. Consequently, this reactive intermediate was trapped by aldehyde 39 through a Lewis acid-promoted enantioselective aldol-type addition, yielding the chiral building blocks 40 with high levels of stereocontrol (Scheme 9.11). It should be noted that the presence of acidic Zr catalyst can also suppress the undesired irreversible intramolecular proton transfer of the oxonium ylide to benefit reaction pathway control. 

Chiral //A(oxazolinc) ligands disubstituted at the carbon atom linking the two oxazolines by Frechet-type polyether dendrimers coordinated with copper(II) triflate were found to provide good yields and moderate enantioselectivities for Mukaiyama aldol reactions in water that are comparable with those resulting from the corresponding smaller catalysts.291 AgPF6-BINAP is very active in this reaction and the addition of a small amount of water enhanced the reactivity.292... 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

Some of the most impressive advances in the area of catalytic, enantioselective aldol addition reactions have taken place in the development of catalytic methods for enantioselective acetate aldol additions, a reaction type that has long been recalcitrant. Thus, although prior to 1992 a number of chiral-auxiliary based and catalytic methods were available for diastereo- and enantiocontrol in propionate aldol addition reactions, there was a paucity of analogous methods for effective stereocontrol in the addition of the simpler acetate-derived enol silanes. However, recent developments in this area have led to the availability of several useful catalytic processes. Thus, in contrast to the state of the art in 1992, it is possible to prepare acetate-derived aldol fragments utilizing asymmetric catalysis with a variety of transition-metal based complexes of Ti(IV), Cu(II), Sn(II), and Ag(I). 

The capability of L-proline - as a simple amino acid from the chiral pool - to act like an enzyme has been shown by List, Lemer und Barbas III [4] for one of the most important organic asymmetric transformations, namely the catalytic aldol reaction [5]. In addition, all the above-mentioned requirements have been fulfilled. In the described experiments the conversion of acetone with an aldehyde resulted in the formation of the desired aldol products in satisfying to very good yields and with enantioselectivities of up to 96% ee (Scheme 1) [4], It is noteworthy that, in a similar manner to enzymatic conversions with aldolases of type I or II, a direct asymmetric aldol reaction was achieved when using L-proline as a catalyst. Accordingly the use of enol derivatives of the ketone component is not necessary, that is, ketones (acting as donors) can be used directly without previous modification [6]. So far, most of the asymmetric catalytic aldol reactions with synthetic catalysts require the utilization of enol derivatives [5]. The first direct catalytic asymmetric aldol reaction in the presence of a chiral heterobimetallic catalyst has recently been reported by the Shibasaki group [7]. 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

Enantioselective aldol-type reactions were achieved by addition of chiral diamines, readily prepared from (5)-proline, to the reaction mixture [29]. Sn(II) has three vacant orbitals, and after coordination of two nitrogen atoms one vacant orbital still... 

Trimethylsilyloxy)furan can also be used as a functionalized silyl enol ether for the asymmetric catalytic aldol-type reaction. Figadere has reported that the reaction of aliphatic aldehydes with the siloxyfuran catalyzed by BINOL-derived titanium complex provides the diastereomeric mixtures with high enantioselectivity (Sch. 42) [107], The addition reaction proceeds at the y position of the siloxyfuran to give butenolides of biological and synthetic importance. 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

The original methods for directed aldol and aldol-type reactions of aldehydes and acetals with silyl enolates required a stoichiometric amount of a Lewis acid such as TiCh, Bl i-OI y, or SnCl.j [18]. Later studies have introduced many Lewis acids which accelerate these processes with a catalytic quantity (vide infra). In addition, it has been found that fluoride ion sources also work as effective catalysts of the aldol reaction [19]. In the last decade, much attention has been paid for the development of diastereo- and enantioselective aldol reactions [20, 21], aqueous aldol reactions using water-stable Lewis acids [22], and novel types of silyl enolate with unique reactivity. 

Vinylogous aldol-type reaction of aromatic and heteroaromatic aldehydes with silyl dienol ethers 21.115, derived from a,p-unsaturated esters, also proceeded smoothly, furnishing exclusively the y-addition products 21.116 (>99 1) with high enantioselectivity in the range of 82-98%... 

Kobayashi and coworkers reported a highly enantioselective approach to aldol-type products via addition of enecarbamates (85a-c) to ethyl glyoxylate (12) and subsequent hydrolysis (Scheme 17.17) [22]. A complex prepared from CuCl04 4CH3CN and chiral diimine (86) was found to catalyze additions in excellent yields and enantioselectivities. In reactions of a-substituted enecarbamates, E-enecarbamates (85b) gave antiadducts, while Z-enecarbamates (85c) provided syn adducts. Diastereo-and enantioselectivities were outstanding in both cases, even at very low catalyst loadings. 

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