Diels-Alder reactions aluminium

The effect of ligands on the endo-exo selectivity of Lewis-acid catalysed Diels-Alder reactions has received little attention. Interestingly, Yamamoto et al." reported an aluminium catalyst that produces mainly exo Diels-Alder adduct. The endo-approach of the diene, which is normally preferred, is blocked by a bulky group in the ligand. 

It has been established that alkoxy alkenylcarbene complexes participate as dienophiles in Diels-Alder reactions not only with higher rates but also with better regio- and stereoselectivities than the corresponding esters [95]. This is clearly illustrated in Scheme 51 for the reactions of an unsubstituted vinyl complex with isoprene. This complex reacts to completion at 25 °C in 3 h whereas the cycloaddition reaction of methyl acrylate with isoprene requires 7 months at the same temperature. The rate enhancement observed for this complex is comparable to that for the corresponding aluminium chloride-catalysed reactions of methyl acrylate and isoprene (Scheme 51). 

Table 3.1 Facialselectivity" in the aluminium chloride catalyzed Diels-Alder reactions of 4-, 5-and 6-substituted 2-cyclohexenones 5 with dienes 1-3...

A number of stereospecific intramolecular Diels-Alder reactions of trienones leading to c -fused products have been described. The ketone 34 forms solely compound 35 on treatment with aluminium trichloride at 110°C (equation 25)30. The lower homologue 36 undergoes a spontaneous cyclization to 37 below 20 °C (equation 26)31 and the isomeric ketones 38 and 40 similarly give 3932 and 4133, respectively (equations 27 and 28). 

The second well-known and much-used carbon-carbon bond forming reaction is a [4 + 2]-cycloaddition, the Diels Alder reaction. Very many chiral Lewis acid catalysts have been used to promote this reaction and a pot-pourri of organo-aluminium, -boron and -copper catalysts are described, in brief, below. 

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. 

SCHEME 6. Enantioselective Diels-Alder reaction induced by a chiral aluminium-containing Lewis acid88... 

The Diels-Alder reaction of enantiomerically pure chiral aery he esters with cyclopen-tadiene leads to a pair of diastereomers. Their ratio depends strongly on the choice and amount of Lewis acid catalyst (Scheme 8)117. While titanium tetrachloride leads preferentially to the (2A )-diastercorner with high selectivity, ethyl aluminium dichloride gives the (2S )-diastereomer in only 56% de. 

A recently published full account of another synthesis [69] of the same alkaloid starting from the /rans-cinnamic ester 264 represented a different approach (ACD -> ACDB) to ( )-lycorine (Scheme 42). An intramolecular Diels-Alder reaction of 264 in o-dichlorobenzene furnished the two diastereomeric lactones 265 (86%) and 266 (5%) involving the endo and exo modes of addition respectively. The transposition of the carbonyl group of 265 to 267 was achieved by reduction with lithium aluminium hydride, followed by treatment of the resulting diol with Fetizon s reagent, which selectively oxidised the less substituted alcohol to give isomeric 5-lactone 267. On exposure to iodine in alkaline medium 267 underwent iodolactonisation to afford the iodo-hydroxy y-lactone 268. The derived tetrahydropyranyl ether... 

A good mediator for the hetero Diels-Alder reaction of aldehydes is the bulky, oxygenophilic aluminium tris(2,6-diphenylphenoxide) (ATP) 2-19 developed by Yamamoto [78] which allows the differentiation between two sterically discriminated aldehydes. Thus, reaction of a mixture of 2-10,2-16 and 2-17 in the presence of 2-19 gave nearly exclusively 2-15, whereas in the presence of BF3-OEt2 a 1.3 1 mixture of 2-15 and 2-18 was formed (Fig. 2-5). 

Alder Ene Reactions. Like the Diels-Alder reaction, Alder ene reactions usually take place only when the enophile has a Z-substituent, the regiochemistry is that expected from the interaction of the HOMO of the ene and the LUMO of the enophile, and Lewis acids increase the rate. All these points can be seen in the reaction of /3-pinene with the moderately activated enophile methyl acrylate, which takes place at room temperature in the presence of aluminium chloride, but which would probably not have taken place easily without the Lewis acid. 

Three reactions, which were known from the literature to be catalyzed by Lewis acids were selected as test reactions. A, was the Reetz alkylation of silyl enol ethers with -butyl chloride for which titanium tetrachloride is known to be useful [52]. B, was the Diels-Alder reaction between furan and acetylenedicarboxylic ester for which aluminium trichloride is a good catalyst [53]. C, was a Friedel-Crafts acylation for which aluminium trichloride is the preferred catalyst [54]. The reactions are summarized in Scheme 6. 

Middleton established that reaction of 1,2-dialkylhydrazines with sulfur and reduction of sulfinylhydrazines (R2N—N=S=0) with lithium aluminium hydride yielded highly colored N-thionitrosoamines (95), which are stable at < ca. -30°C (66JA3842). However, it was deduced from spectroscopic data that these were not true RN=S species a high contribution from the dipolar resonance form accounts for their stability. Nonetheless, compound 95 will act as a 277 component in an inverse electron demand Diels-Alder reaction with a tetrazine derivative to yield triazole 96 (79CZ230). 

B) Diels-Alder reaction of furan and acentylenedicarboxylic ester, for which aluminium trichloride is known to be useful.[5]... 

The starting materials, frans-3,4-methylenedioxycinnamyl alcohol (61a) and frans-2-methoxy-3,4-methylenedioxycinnamyl alcohol (61b) were prepared from the corresponding benzaldehyde via substituted ethyl cinnamate by means of the Horner-Emmons reaction and lithium aluminium hydride reduction. Condensation of compound (61 a) or (61 b) with compound (47) gave compound (62a) or (62b), respectively, followed by ring closure to afford compound (63a) or (63b). Intramolecular Diels-Alder reaction of compound (6 2) led to the formation of the aromatized compounds as by-product in both cases. Moreover, in the reaction of... 

In general the inverse electron-demand Diels-Alder reaction is carried out using stoichiometric amounts of Lewis acid "catalysts (SnCU, TiCU, TiCl2(OR)2, MAD (methylaluminium bis(2,6-di-fert-butyl-4-methylphenoxide) and MAPh (methyl-aluminium bis(2,6-diphenylphenoxide) [15]) at low temperatures (-90 to 0 °C). Before the [3 + 2] cycloaddition with an electron-poor alkene can take place, the first-formed nitronate has to be separated from the Lewis acid catalyst by an aqueous work-up and chromatography [13, 16]. Probably complexation of the Lewis acid catalyst to the nitronate dipole inactivates the dipole and hinders the 1,3-dipolar cycloadditions from taking place [17]. 

It is of interest that the pyridine (17) can be synthesised by intramolecular Diels-Alder reaction of (16) since 2-arylisoxazoles are not useful components in intermolecular Diels-Alder reactions Ketimines react with acrylamide and methylacrylamide in the presence of aluminium chloride to afford 2-oxotetrahydropyridines by a C - alkylation pathwayJ34 however 4-oxopyridines result from the reaction of ketimines with ethyl phenylpropiolate using the same catalyst (Scheme 4).35... 

The Diels-Alder reactions of a-terpinene with acroleinand with methyl acrylate have been examined the presence of aluminium chloride in the latter case alters the stereochemistry of the products considerably. Of the four products formed (141a—d), the endo (141c + 141d) exo (141a + 141b) ratio is 71 29 for the thermal reaction, but 96 4 for the catalysed reaction. 

The most interesting series of observations in this field have been made on the catalytic action of Lewis acids, which are also effective catalysts of Diels-Alder reactions (Section 4.1.6). In the presence of BF3 or its derivatives it has been possible to obtain 1,3-cycloadditions that do not proceed under uncatalysed conditions, e.g. those of benzonitrile oxide to aliphatic nitriles and carbonylic compounds and to oximes . The method has been applied also to the cycloaddition of diazomethane to CN multiple bonds, by using alkyl aluminium halides . Lewis acid catalysts probably act by making the dipolarophiles more polar, through complexing. 

Schreiner et al. developed thiourea catalyst as a promising hydrogen donor, which has more benefit in solubility, synthesis and catalytic mrn over number compared with urea catalyst, in the Diels-Alder reaction of A-crotonyloxazolidinone and cyclopentadiene [22,23] (Table 9.7). A,A -Di[3,5-bis(trifluoromethyl)phenyl]thiourea accelerates the reaction and improves stereoselectivity (run 4) similar to a metal catalyst such as aluminium chloride (AICI3) (mn 2) or titanium chloride (TiCls) (run 3). 

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