Asymmetric reactions Mukaiyama aldol reaction

The asymmetric vinylogous Mukaiyama aldol reaction was applied in several natural product syntheses, such as macquarimicins <2003JA14722, 2004JA11254>, leucascandrolide A <2002AGE4098, 2003JOC9274>, and dactylo-lide <2005AGE3485>. 

A convergent total synthesis of polyene macrolide roflamycoin was achieved by S.D. Rychnovsky and co-workers." " In their approach, they introduced the C25 stereocenter via an asymmetric catalytic Mukaiyama aldol reaction utilizing Carreira s chiral titanium catalyst." ... 

Scheme 2.27 Synthesis of dihydropyrones via asymmetric, vinylogous Mukaiyama aldol reactions (TBAT, tetra-n-butylammonium difluorotriphenylsiliconate).

Curti C, Ranieri B, Battistini L, Rassu G, Zambrano V, Pelosi G, Casiraghi G, Zanardi F (2010) Catalytic, asymmetric vinylogous mukaiyama aldol reactions of pyrrole- and furan-based dienoxy silanes how the diene heteroatom impacts stereocontrol. Adv Synth Catal 352 2011-2022... 

SCHEME 8.55. The catal)4ic asymmetric vinylogous Mukaiyama aldol reaction by Simsek and Kalesse. 

For example in the so-called Mukaiyama aldol reaction of an aldehyde R -CHO and a trimethylsilyl enol ether 8, which is catalyzed by Lewis acids, the required asymmetric environment in the carbon-carbon bond forming step can be created by employing an asymmetric Lewis acid L in catalytic amounts. 

Jacobsen epoxidation 359 -, Katsuki epoxidation 361 -, Mukaiyama-aldol reaction 367 f. -, oxime ether reduction 363 -, Sharpless asymmetric dihydroxyla-tion 361... 

Asymmetric Mukaiyama aldol reactions have also been performed in the presence of Lewis-acid lanthanoid complexes combined with a chiral sulfonamide ligand. Similar enantioselectivities of about 40% ee were obtained for all... 

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

Using chiral catalysts, not only various enantioselective Mukaiyama and vinylogous Mukaiyama aldol reactions have been developed but also asymmetric reactions of a,a-difluoro silyl enol ethers (1) with carbonyl compounds have been reported ... 

Carreira EM (1999) Mukaiyama aldol reaction. In Jacobsen EN, Pfaltz A, Yamamoto H (eds) Comprehensive asymmetric catalysis, vol III. Springer, Berlin Hidelberg New York, p 997... 

Studies of catalytic asymmetric Mukaiyama aldol reactions were initiated in the early 1990s. Until recently, however, there have been few reports of direct catalytic asymmetric aldol reactions [1]. Several groups have reported metallic and non-metallic catalysts for direct aldol reactions. In general, a metallic catalysis involves a synergistic function of the Bronsted basic and the Lewis acidic moieties in the catalyst (Scheme 2). The Bronsted basic moiety abstracts an a-pro-ton of the ketone to generate an enolate (6), and the Lewis acidic moiety activates the aldehyde (3). 

Catalysis with Bisoxazoline Complexes of Sn(II) and Cu(II). The bisoxazoline Cu(IT) and Sn(II) complexes 81-85 that have proven successful in the acetate additions with aldehydes 86,87, 88 also function as catalysts for the corresponding asymmetric propionate Mukaiyama aldol addition reactions (Scheme 8B2.8) [27]. It is worth noting that eithersyn or anti simple diastereoselectivity may be obtained by appropriate selection of either Sn(II) or Cu(II) complexes (Table 8B2.12). 

Keck [63] and Carreira [64] have independently reported catalytic asymmetric Mukaiyama aldol reactions. Keck et al. also reported the aldol reaction of an a-benzyloxy aldehyde with a Danishefsky s diene. The aldol product was transformed to the corresponding HDA-type product through acid-catalyzed cyclization. In these reactions, the catalyst that is claimed to... 

Asymmetric Mukaiyama aldol reactions in aqueous media [EtOH-H20 (9 1)] were reported with FeCl2 and PYBOX ligands 27a [36] and 27b [37]. The latter provides product 28 with higher yield and diastereo- and enantioselectivity (Scheme 8.9). The ee values given are for the syn-diastereoisomer. Whereas ligand 27a is a derivative ofL-serine, compound 27b has four stereogenic centers, since it was prepared from... 

Scheme 8.9 Asymmetric Mukaiyama aldol reactions with Fe(ll)-PYBOX catalysts.

Table 9.2 Asymmetric Mukaiyama aldol reactions catalyzed by chiral quaternary ammonium fluorides4b with various methods of preparation.

Campagne and Bluet recently reported the catalytic asymmetric vinylogous Mukaiyama aldol (CAVM) reaction of aldehydes with dienol silyl ether 15 using chiral ammonium fluorides as an activator. For example, the CAVM reaction of isobutyr-aldehyde with 15 in the presence of 10 mol% of 4b in THF at room temperature led to the formation of the vinylogous aldol product 16 in 70% yield with 20% ee. The ee-value was improved to 30% by conducting the reaction at 0 °C (Scheme 9.6) [16]. 

Asymmetric lanthanide complexes derived from lanthanide triflates and a chiral bidentate sulfonamide ligand were applied to the Mukaiyama aldol reaction (Scheme 19) [299]. Enantiomeric excesses were moderate and the reaction proceeded best in CH2C12 solvent and with ytterbium as metal center. 

Scheme 19. Mukaiyama aldol reaction mediated by asymmetric sulfonamide complexes...

Figure 45. Catalytic, asymmetric Mukaiyama aldol reaction promoted by die chiral Yb complex.

Fujiwara has reported a unique chiral lanthanoid(II) alkoxide-promoted asymmetric Mukaiyama aldol reaction.38 Stoichiometric amounts of the chiral alkoxide, however, were required for good enantioselectivity. 

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