Diastereofacial selectivity Lewis acids

Keywords reactivity, regioselectivity, diastereoselectivity, diastereofacial selectivity, Lewis acids... 

The Lewis acid-catalyzed addition of silyl kelene acetals occurred m high yield, and when the ketene acetal bore a substituent, the reactions occurred with modest diastereofacial selectivity [d] (equation 7) (Table 3)... 

The diastereofacial selectivity of Lewis acid promoted reactions of allylsilancs with chiral aldehydes has been thoroughly investigated58. Aldehydes with alkyl substituted a-stereogenic centers react with a mild preference for the formation of Cram products, this preference being enhanced by the use of boron trifluoride-diethyl ether complex as catalyst58. 

Allyl(trimethyl)silanes react efficiently with Lewis acids to give the corresponding tertiary alcohols67. Although only modest diastereofacial selectivity was observed for reaction with menthyl esters67, improved selectivity was found for chiral a-oxo imides68 and a-oxo amides derived from proline69. 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

In most reported cases, the covalently bound chiral auxiliary has been attached to the dienophile via an acyl linkage, but there are also many examples known in which the auxiliary has been attached to the diene via an acyl, alkyl or heteroatom linkage, the first example of the latter being Trost s diene147. Lewis acids are often added to the reaction mixtures when the chiral auxiliary attached to the dienophile contains an additional Lewis basic site. This is not only to enhance the reaction rate, but especially to enhance the diastereofacial selectivity by complexing to the dienophile in a bidentate fashion. This makes the dienophile more conformationally rigid. 

Cadogan and coworkers160 developed a fructose-derived l,3-oxazin-2-one chiral auxiliary which they applied in the Diels-Alder reactions of its iV-enoyl derivatives 246 with cyclopentadiene using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded mixtures of endo 247 and exo 248 (equation 68). The catalyst binds to the chiral dienophile in a bidentate fashion (co-ordination to both carbonyl groups). As a consequence, the dienophile is constrained to a rigid conformation which accounts for the almost complete diastereofacial selectivities observed. 

Brimble and coworkers172 reported the asymmetric Diels-Alder reactions between quinones 265 bearing a menthol chiral auxiliary and cyclopentadiene (equation 73). When zinc dichloride or zinc dibromide was employed as the Lewis acid catalyst, the reaction proceeded with complete endo selectivity, but with only moderate diastereofacial selectivity affording 3 1 and 2 1 mixtures of 266 and 267 (dominant diastereomer unknown), respectively. The use of stronger Lewis acids, such as titanium tetrachloride, led to the formation of fragmentation products. Due to the inseparability of the two diastereomeric adducts, it proved impossible to determine which one had been formed in excess. 

Furthermore, regioselectivities89 as well as the diastereofacial selectivities90,91 may be increased in the presence of Lewis acids (Table 8). For instance, AICI3 OEt2 improves the ewrfo-selectivity of the reaction of cyclopentadiene and methyl acrylate from 82% to 98%87. The astonishing rate accelerations, the improved yields and higher selectivities make the Lewis acid catalysed Diels-Alder reaction one of the most important organic reactions. 

The diastereofacial selective imine-ene reactions with a-imino esters prepared from (—)-8-phenylmenthyl glyoxylate have provided an efficient entry to the asymmetric synthesis of a-amino acids, and a Lewis acid-mediated intramolecular imine-ene reaction has been used for the key spirocyclization step in a recent synthesis of (—)-perhydrohistrionicotoxin. Asymmetric azo-ene reactions have been effected using the chiral azo-enophile, di-(—)-(lR,2S)-2-phenyl-l-cyclohexyldiazenedicarboxylate. ... 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

Lewis acid-catalyzed stereoselective addition of crotylsilanes to chiral 74 has been studied in detail111,112. The presence of the chiral auxiliary at C2 (e.g. p-tolylsulfinyl or menthoxy carbonyl group) induces the diastereofacially selective addition of cyclopentenones with crotylsilanes. Thus, ( )-crotylsilane favors the erythro product, whilst (Z)-isomer favors the threo product. High enantioselectivity is observed in both reactions (equation 48). In a similar manner, conjugated addition of allylsilane to 75 proceeds with high efficiency (equation 49)113. Interestingly, the yield and enantiomeric excess of the product is dependent on the amount of TiCL used and the best selectivity... 

Diastereofacial selectivity in the a-allylation of cyclic a-acyloxy amides 259 derived from succinic or phthalic anhydride can be controlled by the Lewis acid. Thus, while TiCLt gives 260, allylation promoted by SnCLt affords 261393. No rationalization has been offered. 

Saigo and co-workers reasoned that, by analogy, high levels of diastereofacial discrimination could be achieved in the Lewis acid-mediated Diels-Alder reaction of dienes with oxazolidinone 108-derived dienophiles. Indeed, excellent regioselectivities (endo. exo) and diastereoselectivities were reached in the Diels-Alder reaction of 109 with cyclic and acyclic dienes using Et2AlCl as the activator (Scheme 24.28).107 The selectivities obtained actually surpassed those reported with cis-1 -amino-2-indanol 1 as the chiral auxiliary (93% de) (see Scheme 24.16).82 The additional bulk... 

However, a reversal of the diastereofacial selectivity may arise when the substrate has, in a or f) position of the side chain, a group prone to complexation with the Lewis acid. Then, the use of bidentate Lewis acids such as MgBr2, TiCU or ZnCL allows the reaction to proceed under a chelation control model, providing preferentially the syn adduct for a 1,4-chelation and the anti adduct for a 1,5-chelation. This was exploited in the stereoselective synthesis of both diastereomers, simply by changing the chelation conditions on the substrate18. An impressive amount of work was done with various a-alkoxy aldehydes19-23 as a route to carbohydrate chemistry. Similarly, a-amino aldehydes were used as substrates for /3-amino alcohol synthesis24,25. 

Indium-mediated allylation of the sugar derivatives in aqueous media proceeds with high anti diastereofacial selectivity in the presence of ytterbium triflate as a Lewis acid (Equation (18)).173... 

Diastereofacial-setective intramolecular Diels-Alder reactions. Trienecarbox-imides derived from ahiral oxazolidones undergo Lewis-acid-catalyzed intramolecular Diels-Alder reactions With high endo- and diastereofacial selectivity (endo/exo 100 1). 

The Lewis acid catalyzed additions of silyl ketene acetals to (5)-8 occur in high yield to give products 9 and, when the ketene acetal bears a substituent, the reactions occur with modest diastereofacial selectivity (Table 1). ... 

Poor (<4% de) to modest (56% de) amounts of diastereofacial selection is observed in the cycloaddition of nitrile oxides to optically active acrylates. The plan in each case, of course, was to use a chiral auxiliary which would preferentially shield one of the two ir-faces of the dipolarophile. Of the auxiliaries used, the sulfonamide esters derived from (+)-camphorsulfonyl chloride worked best, the menthyl esters derived from (-)-menthol the poorest (<4% de). As illustrated in Table 19, changes in both temperature and solvent had either no or little affect on the product ratios. Unlike Diels-Alder reactions, the addition of Lewis acids, specifically Et2AlCl, EtAlCh and TiCL, resulted in significant decreases in both the rate of cycloaddition and isolated yield, without an appreciable change in diastereomer ratio. ... 

In the absence of Lewis acid the stereochemical outcome was controlled by the conformation of the starting radicals XIII (Sch. 11). Divalent Lewis acids such as MgBr2 or Mgl2 could alter the structure of the transition state XIV to the bidentate chelate, thus changing the diastereofacial selectivity of the addition reaction. 

ZnCl2-OEt2 accelerated the reaction sufficiently, high diastereofacial selection needed 2 equiv. Lewis acid. It was noted that ethereal zinc halides acted both as radical initiators and as chelating agents, whereas BF3 OEt2 and SnC did not show such activity. 

In Lewis acid-promoted Diels-Alder reactions of cyclopentadiene with the acrylate of (iS )-ethyl lactate, good diastereofacial and endolexo selectivity are obtained with SnCU (84 16 endolexo = 18 1) and TiCU (85 15 endolexo = 16 1) [104]. It is interesting to note that boron, aluminum, and zirconium Lewis acids give the opposite diastereofacial selectivity (33 67 to 48 52). 

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