Lewis acids diastereoselective reactions

The Lewis acid mediated reaction of a-alkoxycarbamates 1 with -/-oxygenated alkylLin compound 2 proceeds in certain cases with very high diastereoselectivity83. The yield and the diastereomeric ratio appear to depend highly on the Lewis acid used and the substituents in the carbamate. While with R1 = C6H5 and R2 = CH, sole formation of the on//-isomer was observed, for other substituents the, y -isomer is obtained either exclusively or predominantly. The reason for this variable diastereoselectivity is not clear at present. 

The Lewis acid catalyzed reactions of silyl enol ethers with nitroalkenes have been reviewed, however the diastereoselectivity of these reactions has not been addressed17. 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

The applicability of axially chiral 1, l -binaphthalcnc-8,8 -diol in asymmetric Diels-Al-der reactions was studied by Fuji and colleagues190. They studied the Lewis acid catalyzed reaction of the unsymmetrically substituted maleate ester of 1,1 -binaphthalene-8,8 diol 302 with cyclopentadiene. The diastereoselectivity proved to depend strongly on the Lewis... 

A wide range of variously substituted thiochromans has been obtained from the readily accessible ot-(benzotriazo-lyl)methyl thioethers by their Lewis acid-catalyzed reaction with styrenes. Initial loss of the benzotriazole unit generates a thionium cation which undergoes an efficient cationic cycloaddition to the alkene. The reaction, which generally proceeds with high diastereoselectivity, is considered to occur in a stepwise manner rather than as a concerted [4++2] process (Scheme 174) <2001JOC5595>. 

Glyoxylate ene reactions. The diastereoselectivity of the ene reaction of methyl glyoxylate (1) with 2-butene (2) can be controlled by the choice of the Lewis acid catalyst. Reactions catalyzed by SnCl4 with either (E)- or (Z)-2 proceed in quan-tative yield and fairly high syn-selectivity. The reaction catalyzed by (CH,)2A1C1 proceeds in low yield (5%) but with high onh-selectivity, particularly in the reaction... 

Scheme 18 Diastereoselectivities of the Lewis acid catalyzed reactions of benz-hydryl chloride with (it)- and (Z)-2-butene. Further products, arising from hydride shifts, are described in Scheme 21. (From Ref. 19.)...

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. 

Highly diastereoselective nitroaldol reactions <2003TL8681> and Lewis acid-catalyzed reactions with furan derivatives <2000PAG1589> on enantiopure glyoxylic acid derivative 586 (R = H, X = 0) were performed. 

Heathcock, C. H., Hug, K. T., Flippin, L. A. Acyclic stereoselection. 27. Simple diastereoselection in the Lewis acid mediated reactions of... 

Oxazolidine 134 is a masked trifluoroacetaldehyde imine that generates in situ the corresponding imine 135 under Lewis acid catalysis conditions. Lewis acid-catalyzed reactions of 134 with TMS-cyanide and ketene silylacetal provide adducts 136 in high yields with good diastereoselectivities (see Scheme 9.29) [56]. Conventional chemical transformation of 137 produces 3-amino-4,4,4-trifluorobutanoic acid 138. Similarly, tri-fluoroacetone oxazolidine 139 is used for the synthesis of 2-trifluoromethylalanine 142... 

The Lewis acid-promoted reaction of a-amino aldehydes with chiral -2-bute-nylsilanes 55 has also been examined [40]. In the reaction of (S)-56, it was determined that the stereochemical outcome of the reaction is largely determined by the absolute configuration of the C-SiR3 center. The reaction of both the (R)- and (S)-2-butenylsilanes proceeded in high yield, but the (S)-2-butenylsilane gave poor levels of diastereoselectivity (Scheme 10-21). 

The preparation of vicinal polyol triads requires the placement of oxygen functionality at the y-position of the allylic stannane. The Lewis acid-promoted reaction of y-alkoxyallylstannanes with achiral aldehydes was first reported by Koree-da (Scheme 10-60) [98]. The reactions proceed in moderate to high yield and with good diastereoselectivity to produce the homoallylic alcohols. As in the case of simple ( )- and (Z)-138, the reactions are stereoconvergent giving rise to predominantly the syn diastereomer independently of olefin geometry. It was speculated that the reaction proceeds via an acyclic transition structure. 

Keck [99] first disclosed the Lewis acid-promoted reaction of a y-siloxy or al-koxyallylstannane with either a- or / -alkoxy aldehydes (Scheme 10-61). Reaction of the a-alkoxy aldehyde 141 with the allylstannane 142 affords the homoallylic alcohol 143 as the only product. Reaction of the / -alkoxy aldehyde 52 with the allylstannane 142 also proceeds in high diastereoselectivity ( 50/l) to produce the homoallylic alcohol 144. The stereochemical outcome of these reactions is consistent with a chelation-control mechanism. 

Asymmetric Diels-Alder reactions of a, ft-unsaturated acids.2 The acrylate ester (2) of this alcohol (1) undergoes Lewis acid-catalyzed reactions with cyclopentadiene in >97 3 diastereoselectivity. 

Titanium complexes are often encountered in Lewis acid-catalysed reactions. This is certainly true for catalysed aldol reactions. Mikami and Matsukawa demonstrated that titanium/BINOL complexes e.g. complex (7.20) afforded high yield and enantioselectivity in the aldol reactions of thioester ketene silylacetals with a variety of aldehydes. In contrast to some of the aldol reactions described above, the stereochemistry of the adducts is dependant on the geometry of the enol ether. Thus, reaction of the (B)-enol ether (7.21) with aldehyde (7.22) yields the sy -aldol adduct (7.23) predominantly while the (Z)-e.no ether (7.24) results in isolation of the anti-adduct (7.25) as the major product. The authors invoke a closed silatropic ene transition state (structure (7.26) for syn-transition state), substantiated by suitable crossover experiments, to explain the diastereoselectivities... 

Lewis acid-catalyzed reactions of chiral 1-acyloxy-1,3-butadienes with acrolein, methacrolein or quinones proceed endo selective at low temperature in the presence of BF3-OEt2 or B(OAc)3 with moderate to hi diastereoselectivities. 

Compared with chiral nonracemic a-amino carbonyl compounds - which are not suitable substrates for MBH reaction, mainly due to their racemization under normal conditions after prolonged exposure times to catalyst or due to poor diastereoselectivity " a-keto lactams, enantiopure 3-oxo-azetidin-2-ones 168, readily react with various activated vinyl systems promoted by DABCO to afford the corresponding optically pure MBH adducts 169 without detectable epimerization (Scheme 1.69). " However, the Lewis acid-mediated reaction of electron-deficient alkynes with azetidine-2,3-diones 168 as an entry to p-halo MBH adduets was not very sueeessful the coupling product 170 was achieved with concomitant acetonide cleavage as a single ( )-isomer in low yield, in the presence of trimethylsilyl iodide under BF3 OEt2-induced catalysis (Scheme 1.69). 

Rueping and co-workers have reported one of the most impressive examples of a Nazarov cyclization under asynunetric catalysis. They have shown that chiral Bronsted-acid catalysis outperforms the chiral Lewis acid catalysts used to date and have demonstrated the efficient cyclization of a variety of substrates 79 with moderate to excellent diastereoselectivity and good to excellent enantioselectivity. Only low catalyst loadings (2 mol %) are required of chiral acid 81 to catalyze the reaction efficiently. Interestingly, the reaction primarily generates the cw-cyclopentanones 80a, as opposed to the Lewis acid-catalyzed reactions that provide the trans-product (see 73). 

In the reaction of the tin(II) enolate derived from (1) with aldehydes, enantioselectivities are disappointingly low, while good diastereoselectivities are observed. Highly diastereo- and enan-tioselective aldol reactions of propionate derivatives with aldehydes have been achieved by using the ketene silyl thioacetal (7) instead of the tin(II) enolate. The complex (8) produced by mixing tin(n) triflate and the chiral diamine (6) works as an efficient chiral Lewis acid. The reaction of (7) with various aldehydes proceeds smoothly in the presence of (8) and dibutyltin diacetate in dichloromethane to afford the syn aldol adducts in high yields with almost perfect stereochemical control (eq 9). ... 

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