Acids Diethylaluminum chloride

Scheme 7.5 gives some examples of the Reformatsky reaction. Zinc enolates prepared from a-haloketones can be used as nucleophiles in mixed aldol condensations (see Section 2.1.3). Entry 7 is an example. This type of reaction can be conducted in the presence of the Lewis acid diethylaluminum chloride, in which case addition occurs at -20° C.171... 

Epoxytrichloroacetimidates 153 also undergo oxazoline ring formation in the presence of a catalytic amount of Lewis acids.Diethylaluminum chloride was found to be superior to boron trifluoride, which tends to further hydrolyze the oxazoline 154 to the trichloroacetamide. Generally, formation of the six-membered ring oxazine 155 is not favored, but it can be a serious side reaction if the epoxide contains substituents that stabilize the incipient cation generated prior to ring closure. Examples from this study are summarized in Table 8 19 (Fig 8 8 Scheme 8.45). 

Vinyl epoxides can also be ring-opened via an Sn2 sense, as exemplified in the macrocyclization of the epoxy-tethered cyclopentenone 76, which was induced to occur by treatment with lithium 2,2,6,6-tetramethylpiperidide (LTMP) followed by the mild Lewis acid diethylaluminum chloride in THF. The enolate attacked exclusively from the a-position of the... 

Dodecatrienals undergo intramolecular Diels-Alder cyclization in the presence of ethylaluminum dichloride or the milder Lewis acid diethylaluminum chloride at — 78 to -23°. -Example ... 

Usually, more than a stoichiometric amount of these catalysts is required for the reaction to efficiently proceed. Among these Lewis acids, diethylaluminum chloride is an excellent catalyst and 2 molar equivalents of diethylaluminum chloride efficiently accelerated the rearrangement of allyl phenyl ether 1 at room temperature to give the ortho-rearranged product 3 in 93% yield [33]. 

A solution of 1.5 mol equiv of butyllithium in hexane is added to 1.5 mol equiv of a 1 M solution of hexabutylditin in THF at 0 C under nitrogen, and the mixture is stirred for 20 min. The solution is cooled to — 78 °C and a solution of 1.5 mol equiv of diethylaluminum chloride in toluene is added. After stirring for 1 h at — 78 °C, a solution of 0.05 mol equiv of [tetrakis(triphenyl)phosphine]palladium(0) in THF is added followed by a solution of the allyl acetate in THF. The mixture is warmed to r.t., and stirred until the allyl acetate has reacted (TLC). The solution is cooled to 0°C, and an excess of aq ammonia slowly added. After an aqueous workup, the products arc isolated and purified by flash chromatography on silica gel using 1 % triethylamine in the solvent to avoid acid-induced loss of stannane. 

Lewis acids such as zinc chloride, boron trifluoride, tin tetrachloride, aluminum chloride, methylaluminum dichloride, and diethylaluminum chloride catalyze Diels-Alder reactions.22 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the addition is believed to be concerted and enhanced regio- and stereoselectivity is often observed.23... 

The experimental isotope effects have been measured for the reaction of 2-methylbutene with formaldehyde with diethylaluminum chloride as the catalyst,27 and are consistent with a stepwise mechanism or a concerted mechanism with a large degree of bond formation at the TS. B3LYP/6-31G computations using H+ as the Lewis acid favored a stepwise mechanism. 

In most cases, the stereochemical course of heterocyclic addition can be altered by pre-complexation of nitrones with Lewis acids. In the absence of complexation agents (Et2AlCl, TiCLi), addition of lithio-hetaryl derivatives to chiral 3-alkoxy nitrones (292a-d) gives P-alkoxy-a-hydroxylamino-2-alkylhetaryls (346a-d) in good yields with. vy/i-selectivity. In the presence of diethylaluminum chloride the reaction leads to the same adducts, but with anti-selectivity (Scheme 2.150) (Table 2.12) (581). 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

The Lewis acid catalyzed reaction of furan (169) with ketovinylphosphonate 170 produced a mixture of adducts, both of which slowly underwent retro Diels-Alder reactions at room temperature121. When diethylaluminum chloride was used as the catalyst, the endo selectivity (with respect to the keto functionality) was enhanced from 171/172 = 58/42 to 78/22 by raising the reaction temperature from — 25 °C to 0°C (equation 47). This is in agreement with the FMO theory, since initial Lewis acid complexation is with the phosphonate group. 

Sudo and Saigo153 reported the application of ds-2-amino-3,3-dimethyl-l-indanol derived l,3-oxazolidin-2-one 231 as a chiral auxiliary in asymmetric Diels-Alder reactions. The TV-crotonyl and TV-acryloyl derivatives were reacted with cyclopentadiene, 1,3-cyclohexadiene, isoprene and 2,3-dimethyl-l,3-butadiene, using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded the expected cycloadducts in moderate to high yields (33-97%) with high endo selectivities and high de values (92% to >98%). 

Carbohydrates have found widespread use as chiral auxiliaries in asymmetric Diels-Al-der reactions156. A recent example is a study conducted by Ferreira and colleagues157 who used carbohydrate based chiral auxiliaries in the Lewis acid catalyzed Diels-Alder reactions of their acrylate esters 235 with cyclopentadiene (equation 66). Some representative results of their findings, including the ratios of products 236 and 237, have been summarized in Table 9. The formation of 236 as the main product when diethylaluminum chloride was used in dichloromethane (entry 3) was considered to be the result of an equilibrium between a bidentate and monodentate catalyst-dienophile complex. The bidentate complex would, upon attack by the diene, lead to 236, whereas the monodentate complex would afford 236 and 237 in approximately equal amounts. The reversal of selectivity on changing the solvent from dichloromethane to toluene (entry 2 vs 3) remained unexplained by the authors. 

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. 

Taguchi and coworkers175 studied the Lewis acid catalyzed asymmetric Diels-Alder reactions of chiral 2-fluoroacrylic acid derivatives with isoprene and cyclopentadiene. When a chiral l,3-oxazolidin-2-one and diethylaluminum chloride were used as the chiral auxiliary and the Lewis acid catalyst, respectively, a de of 90% was observed for the reaction with isoprene. The reaction with cyclopentadiene afforded a 1 1 mixture of endo and exo isomers with de values of 95% and 96%, respectively. The endo/exo selectivity was improved by using 8-phenylmenthol as the chiral auxiliary. Thus, the reaction... 

Aluminumtriethyl Diethylaluminum chloride Ethylaluminum dichloride Lewis base + Cyclic di- and triolefins Aliphatic ethers Carboxylic acid esters... 

Cycloaddition of N-benzylimines and a diene. Diethylaluminum chloride is the best Lewis acid for promoting addition of N-substituted imines (2) with the activated diene 1 (9,302-303). ... 

Intramolecular Diels-Alder reactions resulting in bridgehead alkenes usually require high reaction temperatures. Consequently catalysts that permit use of lower temperatures are useful. Of a number of Lewis acids studied, diethylaluminum chloride was found to be the most efficient for the intramolecular cycloaddition of the triene 7 to 8 at 21°. The... 

Non-Evans Aldol Reactions. Either the syn- or onri-aldol adducts may be obtained from this family of imide-derived eno-lates, depending upon the specific conditions employed for the reaction. Although the illustrated boron enolate affords the illustrated jyn-aldol adduct in high diastereoselectivity, the addition reactions between this enolate and Lewis acid-coordinated aldehydes afford different stereochemical outcomes depending on the Lewis acid employed (eq 35). Open transition states have been proposed for the Diethylaluminum Chloride mediated, anti-selective reaction. These anfi-aldol reactions have been used in kinetic resolutions of 2-phenylthio aldehydes. ... 

Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3 -diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14). Endo products are obtained with a high level of asymmetric induction (>90% ee) however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15). BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16). ... 

A Lewis acid-mediated two-fold asymmetric Michael addition allows access to c( s-decalin derivatives. The reaction of the trimethylsilylenol ether of acety Icyclohexene with phenylmenthyl acrylate in the presence of Diethylaluminum Chloride (eq 7) yields the decalone in 64% yield (70% de). This has been shown not to be a Diels-Alder reaction. If the reaction is worked-up early, the initial Michael adduct can be isolated. ... 

The optimum catalyst for the reaction of 175 and cyclopentadiene was generated in-situ from one equivalent of the diol and two equivalents of ethyl aluminum dichloride. Presumably this generates a Lewis acid with two dichloroalkoxy aluminum groups per molecule of catalyst. The catalyst generated from diol 181 and one equivalent of diethylaluminum chloride is not very active, possibly because here the catalyst is a di-alkoxy aluminum chloride. The highest induction was observed for a catalyst generated from the diamino substituted diol 187, which was prepared from tartaric acid. 

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