Enantioselective synthesis Mukaiyama aldol reaction

To start with the addition of y-dienolates to aldehydes, the so-called vinylogous Mukaiyama aldol reaction, Campagne et al. studied the applicability of different types of catalyst when using the silyldienolate 115 as nucleophile [121]. In general, many products obtained by means of this type of reaction are of interest in the total synthesis of natural products. It should be added that use of CuF-(S)-TolBinap (10 mol%) as metal-based catalyst led to 68% yield and enantioselectivity up to... 

Silyl enol ethers react with aldehydes in the presence of chiral boranes or other additives " to give aldols with good asymmetric induction (see the Mukaiyama aldol reaction in 16-35). Chiral boron enolates have been used. Since both new stereogenic centers are formed enantioselectively, this kind of process is called double asymmetric synthesis Where both the enolate derivative and substrate were achiral, carrying out the reaction in the presence of an optically active boron compound ° or a diamine coordinated with a tin compound ° gives the aldol product with excellent enantioselectivity for one stereoisomer. Formation of the magnesium enolate anion of a chiral amide, adds to aldehydes to give the alcohol enantioselectively. 

In analogy t 0 the Cu(II) complex systems, the silver(I) -catalyzed aldol reaction is also proposed to proceed smoothly through a Lewis acidic activation of carbonyl compounds. Since Ito and co-workers reported the first example of the asymmetric aldol reaction of tosylmethyl isocyanide and aldehydes in the presence of a chiral silver(I)-phosphine complex (99,100), the catalyst systems of sil-ver(I) and chiral phosphines have been applied successfully in the aldol reaction of tin enolates and aldehydes (101), Mukaiyama aldol reaction (102), and aldol reaction of alkenyl trichloroacetates and aldehydes (103). In the Ag(I)-disphosphine complex catalyzed aldol reaction, Momiyama and Yamamoto have also examined an aldol-type reaction of tin enolates and nitrosobenzene with different silver-phosphine complexes (Scheme 15). The catalytic activity and enantioselectivity of AgOTfi(f )-BINAP (2 1) complex that a metal center coordinated to one phosphine and triflate were relay on solvent effect dramatically (Scheme) (104). One catalyst system solves two problems for the synthesis of different O- and AT-nitroso aldol adducts under controlled conditions. 

Since our group (22) and Hehnchen s (23) independently announced a new class of chiral acyloxyboranes derive from iV-sulfonylamino acids and borane THF, chiral 1,3 -oxazaborolidines, their utility as chiral Lewis acid catalysts in enantioselective synthesis has been convincingly demonstrated (2(5). In particular, Corey s tryptophan-derived chiral oxazaborolidines 10a and 10b are highly effective for not only Mukaiyama aldol reactions (24) but also Diels-Alder reactions (25). More than 20 mol% of 10b is required for the former reaction, however. Actually, the reaction of the trimethylsilyl enol ether derived from cyclopentanone with benzaldehyde afforded the aldoI products in only 71% yield even in the presence of 40 mol%of 10b (24). We recently succeed in renewing 10b as a new and extremely active catalyst lOd using arylboron dichlorides as Lewis acid components (2(5). 

Jergensen and coworkers reported Cu(OTf)2/t-Bu-BOX (13)-catalyzed Mukaiyama aldol reactions between silylketene acetals and pyridine N-oxide aldehydes (78) and (81) (Scheme 17.16) [21]. The chemical efficiencies were high and good to excellent enantioselectivities were observed. This work further expanded the scope of aldehydes capable of bidentate coordination in aldol reactions. The authors utilized aldol adduct (83) in the synthesis of indolizine alkaloid (84). 

The Mukaiyama aldol reaction is a favorable method for the synthesis of P-hydroxy carbonyl compounds in terms of environmental friendliness because the process uses less toxic silyl enolates compared to organotin enolates [52]. Yamagishi and CO workers have examined a BI NAPAg( I)-catalyzed asymmetric Mukaiyama aldol reaction with trimethylsilyl enolates and have found that the reaction is accelerated by BINAP-AgPFe in DMF containing a small amount of water to give the aldol adduct with high enantioselectivity (Scheme 18.14) [53]. 

The Mukaiyama aldol reaction has also been used in the enantioselective asymmetric synthesis of 5-hydroxy-P-keto ester derivatives. Katsuki and coworkers utilized the chiral Cr(salen) complex 69 for the catalysis of the aldol reaction in the presence of water or alcohol. The presence of alcohol in the reaction greatly increases the enantioselectivity of the aldol addition. In the reaction of the silyl enol ether 92 with the aldehyde 93 in the presence of the catalyst 69, triethylamine, and isopropanol yielded the aldol adduct 94 in high yield (87%) and excellent enantioselectivity (97% ee). 

Cyclohepta-3,5-dienone)iron complexes can be stereoselectively methylated and hydroxylated. The electrophile adds exclusively anti to the tricarbonyliron fragment. Double methylation or hydroxylation of the a and a positions is accomplished in high overall yield (Scheme 4-146). Silyl enol ethers adjacent to tricarbonyl(Ti -diene)iron units can be subjected to Mukaiyama aldol reaction with aldehydes to provide aldol adducts with varying diastereoselectivity. This methodology has, for example, been applied to the enantioselective synthesis of the dienetriols streptenol C and D (Scheme 4-147). ... 

Simsek S, Kalesse M. Enantioselective synthesis of polyke-tide segments through vinylogous Mukaiyama aldol reactions. Tetrahedron Lett. 2009 50(26) 3485 3488. 

A series of chiral binaphthyl ligands in combination with AlMe3 has been used for the cycloaddition reaction of enamide aldehydes with Danishefsky s diene for the enantioselective synthesis of a chiral amino dihydroxy molecule [15]. The cycloaddition reaction, which was found to proceed via a Mukaiyama aldol condensation followed by a cyclization, gives the cycloaddition product in up to 60% yield and 78% ee. 

Oxamborolidenes. There are noteworthy advances in the design, synthesis, and study of amino acid-derived oxazaborolidene complexes as catalysts for the Mukaiyama aldol addition. Corey has documented the use of complex 1 prepared from A-tosyl (S)-tryptophan in enantioselective Mukaiyama aldol addition reactions [5]. The addition of aryl or alkyl methyl ketones 2a-b proceeded with aromatic as well as aliphatic aldehydes, giving adducts in 56-100% yields and up to 93% ee (Scheme 8B2.1, Table 8B2.1). The use of 1-trimethylsilyloxycyclopentene 3 as well as dienolsilane 4 has been examined. Thus, for example, the cyclopentanone adduct with benzaldehyde 5 (R = Ph) was isolated as a 94 6 mixture of diastereomers favoring the syn diastereomer, which was formed with 92% ee, Dienolate adducts 6 were isolated with up to 82% ee it is important that these were shown to afford the corresponding dihydropyrones upon treatment with trifuoroacetic acid. Thus this process not only allows access to aldol addition adducts, but also the products of hetero Diels-Alder cycloaddition reactions. 

Mukaiyama and Kobayashi et al. have developed the use of Sn(OTf)2 in diastereose-lective and enantioselective aldol-type reactions [26,27]. Initially, the stereoselective aldol reactions were performed with a stoichiometric amount of Sn(OTf)2 [28], The reaction between 3-acylthiazolidine-2-thione and 3-phenylpropionaldehyde is a representative example of a diastereoselective syn-aldol synthesis (Eq. 17). 

Oxazaborolidenes. Corey has reported the use of a novel oxazaborolidene complex 41 prepared from borane and A-tosyl (5)-tryptophan. This complex functions in a catalytic fashion in enantioselective, Mukaiyama aldol addition reactions (Scheme 8-3) [17]. The addition of ketone-derived enol silanes 42-43 gives adducts in 56-100% yields and up to 93% ee. The use of 1-trimethylsilyloxycyclo-pentene 43 in the addition reactions to benzaldehyde affords adducts 46 as a 94 6 mixture of diastereomers favoring the syn diastereomer in 92% ee. Addition reactions with dienol silanes 44 furnishes products 47 in up to 82% ee. Corey also demonstrated the use of these adducts as important building blocks for the synthesis of corresponding dihydropyrones treatment of 47 with trifluoroacetic acid affords the cyclic product in good yields. 

The aldol reaction and related processes have been of considerable importance in organic synthesis. The control of syn/anti diastereoselectivity, enantioselectivity and chemoselectivity has now reached impressive levels. The use of catalysts is a relatively recent addition to the story of the aldol reaction. One of the most common approaches to the development of a catalytic asymmetric aldol reaction is based on the use of enantiomerically pure Lewis acids in the reaction of silyl enol ethers with aldehydes and ketones (the Mukaiyama reaction) and variants of this process have been developed for the synthesis of both syn and anti aldol adducts. A typical catalytic cycle is represented in Figure 7.1, where aldehyde (7.01) coordinates to the catalytic Lewis acid, which encourages addition of the silyl enol ether (7.02). Release of the Lewis acid affords the aldol product, often as the silyl ether (7.03). 

Shiina I, Saitoh K, Frechard-Ortuno I, Mukaiyama T (1998) Total Asymmetric Synthesis of Taxol by Dehydration Condensation between 7-TES Baccatin III and Protected N-Benzoylphenylisoserines Prepared by Enantioselective Aldol Reaction. Chem Lett 3... 

Scheme 5.67 Evans Mukaiyama aldol and vinylogous aldol reactions mediated by the copper PYBOX catalyst 217 enantioselective synthesis of callipeltoside A building block 225.

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