Diels-Alder reaction Menthol

The Diels-Alder reaction of simple alkoxy alkenylcarbene complexes leads to mixtures of endo and exo cycloadducts, with the endo isomer generally being the major one [96,97]. Asymmetric examples of endo Diels-Alder reactions have also been reported by the use of chiral auxiliaries both on the carbene complex and the diene. Thus, the reaction of cyclopentadiene with chiral alkenylcarbene complexes derived from (-)-menthol proceeds to afford a 4 1... 

Clive and coworkers have reported a total synthesis of calicheamicinone, the aglycon of the antitumor agent calicheamicin starting from the Diels-Alder reaction of methyl 3-nitro-propenoate with ketene acetal (Eq. 8.32).54 An asymmetric Diels-Alder reaction between ketene acetal presented in Eq. 8.32 and 3-nitropropenoate derived from (-)-8-phenyl-menthol affords the optically pure adduct, which can be converted into either enantiomer of calicheamicinone (Eq. 8.33).55... 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

The first organoaluminium complex that catalysed a Diels Alder reaction was formed from menthol and ethylaluminium dichloride. This finding was complemented by work of Corey who showed that the aluminium diamine complex (49) was effective for controlling the stereochemistry of Diels-Alder reactions involving cyclopentadiene and acryloyl and crotonyl amides (e.g. 

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. 

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. 

The Diels-Alder reaction between a 2-fluoroacrylic acid derivative of 8-phenyl-menthol (83) and cyclopentadiene shows high exo- and jr-diastereofacial selectivity (Scheme 30). The C(2) of endocyclic cross-conjugated 2-(acylamino)-l,3-dienes exerts excellent diastereofacial control on the Diels-Alder addition with electron-deficient dienophiles to produce octahydroquinolines. ... 

The first report of an asymmetric Diels-Alder reaction with chiral Lewis acids (252) was made by Russian chemists in 1976 (253). Koga was probably the first to report a meaningful enantioselective Diels-Alder reaction (Scheme 105) in which the cyclopentadiene-methacro-lein exo adduct was obtained in 72% ee with the aid of 15 mol % of a menthol-modified aluminum chloride (254). The ee is highly dependent on the structures of the substrates, and asymmetric induction has not been observed with methyl acrylate as dienophile. Disproportionation... 

Diels-Alder reaction Cyclopentadiene, 78 Menthol, 172 8-Phenylmenthol, 243 Ene reaction 8-Phenylmenthol, 243 Epoxidation... 

Further C6o derivatives of menthol include a menthyl malonate adduct119 and a carbamate derived from l,2-epimino[60]fullerene.429 Resin acid derivatives have been prepared by Diels-Alder reaction of C6o with methyl levopi-marate, whose parent acid can be isolated from rosin.430 Finally, a derivative of a-pinene was synthesized in the context of a study on the photochemically induced addition of allyl stannanes to Cr,o, a reaction presumably proceeding via SET from the stannane to the triplet excited fullerene.431... 

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. ... 

The earliest report of a reaction mediated by a chiral three coordinate aluminum species describes an asymmetric Meerwein-Poimdorf-Verley reduction of ketones with chiral aluminum alkoxides which resulted in low induction in the alcohol products [1]. Subsequent developments in the area were sparse until over a decade later when chiral aluminum Lewis acids began to be explored in polymerization reactions, with the first report describing the polymerization of benzofuran with catalysts prepared from and ethylaluminum dichloride and a variety of chiral compounds including /5-phenylalanine [2]. Curiously, these reports did not precipitate further studies at the time because the next development in the field did not occur until nearly two decades later when Hashimoto, Komeshima and Koga reported that a catalyst derived from ethylaluminum dichloride and menthol catalyzed the asymmetric Diels-Alder reaction shown in Sch. 1 [3,4]. This is especially curious because the discovery that a Diels-Alder reaction could be accelerated by aluminum chloride was known at the time the polymerization work appeared [5], Perhaps it was because of this long delay, that the report of this asymmetric catalytic Diels-Alder reaction was to become the inspiration for the dramatic increase in activity in this field that we have witnessed in the twenty years since its appearance. It is the intent of this review to present the development of the field of asymmetric catalytic synthesis with chiral aluminum Lewis acids that includes those reports that have appeared in the literature up to the end of 1998. This review will not cover polymerization reactions or supported reactions. The latter will appear in a separate chapter in this handbook. 

The first examples of an asymmetric Diels-Alder reaction of a non-chiral diene and a dienophile catalyzed by a chiral Lewis acid were reported by Koga and coworkers in 1979 (Sch. 1 and 16) [3]. The catalysts 4,142 and 143 were prepared from (-)-menthol, (+)-neomenthol and (+)-borneol. The reaction of methacrolein and cyclopentadiene mediated by catalyst 4 gave a 98 2 mixture of exo to endo products and upon separation of these diastereomers by chromatography the exo product 3 was obtained in 69 % yield and 72 % ee. The exo .endo ratios for the other reactions in Sch. 16 were not reported. Low asymmetric induction was observed for acrolein and methyl acrylate with all three catalysts. Moderate induction was observed in the reaction of methacrolein with catalyst 4, and with catalyst 142, but in the latter the enantiomer of 3 was the predominant product. The reaction of methyl acrylate with cyclopentadiene mediated by 10 mol % catalyst 4 was also reported by Kobayashi, Matsumura and Furukawa to give the cycloadduct 141 in 2.9 % ee at 30 °C [37]. These workers also reported that catalyst 4 will give optically active product from the reaction of cyclopentadiene and acrylonitrile, although the optical yield was not determined. 

The first successful examples of enantioselective Diels-Alder reactions catalyzed by chirally modified Lewis acids were reported by Koga [85]. The catalysts were prepared from menthol and AlEt2Cl [86]. Alumina-supported chiral menthoxy aluminum derivatives (64, 65, 66, 67) have been prepared by simple mixing of (-)-menthol, AlEt2Cl, and alumina in toluene under reflux. The reaction of methacrolein with cyclopentadiene (Eq. 20) was conducted with 67 as catalyst at -50 °C and afforded 81 % conversion with 31 % ee [87] Koga reported 57 % ee at -78 °C by use of an homogeneous catalyst [85]. Solid catalyst 69, prepared from silica gel-supported proli-nol 68 and AlEt2Cl (Eq. 21) is also an active catalyst in the same reaction, but with low enantioselectivity [87]. When the same catalyst was attached to crosslinked polystyrene (70) the ee in the reaction was lower [88]. 

Addition reactions to olefins can be used both for the construction and for the functionalization of molecules. Accordingly, chiral catalysts have been developed for many different types of reactions, often with very high enantioselectiv-ity. Unfortunately, most either have a narrow synthetic scope or are not yet developed for immediate industrial application due to insufficient activities and/ or productivities. These reactions include hydrocarbonylation [Ilf], hydrosilyla-tion [12 i], hydroboration [12j], hydrocyanation [12 k], Michael addition [11 g, 121, 12 m], Diels-Alder reaction [11 h, 12n] and the insertion of carbenes in C-H bonds [Hi, 12p, 12q, 38], Cyclopropanation [Hi, 12p, 12q] and the isomerization of allylamines [12 s] are already used commercially for the manufacture of Cilastatin (one of the first industrial processes) [12 r], and citronellol and menthol (presently the second largest enantioselective process) [12t] respectively. 

The Diels-Alder reaction between furan and maleic anhydride is reversible and gives the more stable exo-adduct 100 (also commercially available). This compound contains the bicyclic ring system of ifetroban but is achiral and the key problem is to disrupt symmetry of the adduct 100 in a controlled way. The original synthesis used to make the drug17 converted the adduct 100 into the menthyl acetal 101 as a single enantiomer in four steps and then into the carboxylic acid 102 in another six steps. This strategy amounts to a resolution as each menthol adduct could be isolated by crystallisation of a diastereoisomeric mixture in only about 30% yield. 

A Diels-Alder reaction catalyzed by a chiral Lewis acid was described for the first time in 1979 by Koga et al. [44]. The catalyst was prepared by action of (-)-menthol on EtAlCl2 and gave 72% ee (later revised to 55% ee) in the formation of the exo-cycloadduct between cyclopentadiene and methacroleine. 

In 1979, Koga and coworkers disclosed the first practical example of a catalytic enantioselective Diels-Alder reaction [44] promoted by a Lewis acidic complex, presumed to be menthoxyaluminum dichloride (1), derived from menthol and ethylaluminum di chloride, whose structure remains undefined [45]. This complex catalyzed the cycloaddition of cyclopentadiene with acrolein, methyl acrylate, and methacrolein with enantioselectivities as high as 72% ee. Oxidation of 2 (predominantly exo) followed by recrystallization actually lowered the ee ... 

Titanium-pillared montmorillonites (Ti-PILC) modified with tartrates were described as heterogeneous Sharpless epoxidation catalysts [33] as well as for the oxidation of aromatic sulfides [34]. Metal oxides modified with histamine showed modest efficiencies for the kinetic resolution of activated amino acid esters (kj /k5 2) [35]. Silica or alumina treated with diethylaluminium chloride and menthol catalyzed the Diels-Alder reaction between cylopentadiene and methacrolein with modest enantioselectivities of up to 31% ee [36]. ZeoHte HY, modified with chiral sulfoxides had remarkable selectivities for the kinetic resolution of 2-butanol (k /kj =39) but unfortunately the catalyst is not very stable... 

The first approach to this problem was to attach the chiral auxiliary to the diene by a vinylogous trans-esterification reaction of chiral alcohols with the 3-alkoxy enones (Scheme 21). This reaction was used to construct a variety of chiral dienes including the menthol and phenmenthol dienes (55a) and (55b) by transesterification followed by enol silylation using the Simchen procedure (RsSiOTf taN). However, these dienes exhibit poor diastereofacial selectivity despite the precedent for high stereochemical control in homo Diels-Alder reactions by the use of similar auxiliaries on a,P-unsaturated enones. ... 

Table 19 Asymmetric Diels-Alder Reactions using Chiral Catalysts Comparison of Eu(hfc)j with Menthol...

Fumarates. Asymmetric cycloaddition to fumarates has been accomplished by modification of either one or both ends of the diacid. In fact, addition of butadiene to dimenthyl fumarate, reported by Walborsky in 1961, was the first highly selective (89% ds) asymmetric Diels-Alder reaction ever recorded [186,187]. Scheme 6.45 shows examples of cycloadditions of several dienes to dimenthyl fumarate [186-189]. Scheme 6.45a illustrates the presumed reactive conformation of dimenthyl fumarate This conformation features (c/. Figure 6.13a) an trans conformation at C1-C2, cis orientation of the ester ligand relative to the carbonyl oxygen, and orientation of the menthyl moiety to relieve Af3 strain. In this conformation, preferred approach of the diene is from the (rear) C2 Si face. In addition to menthol (Figure 6.12a) 1-mesityl trifluoroethanol (Figure 6.12d) has beep used as a Z w-auxiliary [169]. 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

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