Benzaldehydes Diels-Alder reactions

In 1973 two papers appeared almost simultaneously (73T101, 73CPB2026) describing the formation, as a minor product, of 3,4,5-trimethoxycarbonyl-l-phenylpyrazole (346) in the reaction between benzaldehyde phenylhydrazone and DMAD (EC=CE). To account for the formation of (346) George et al. (73T101) proposed a tentative mechanism (Scheme 29) involving a Diels-Alder reaction of type (a Figure 25), followed by a retro-Diels-Alder elimination of methyl phenylpropiolate (347). 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde 9 with the very reactive diene, Danishefsky s diene 10, catalyzed by aluminum complexes has been investigated from a theoretical point of view using semi-empirical calculations [27]. The focus in this investigation was to address the question if the reaction proceeds directly to the hetero-Diels-Alder adduct 11, or if 11 is formed via a Mukaiyama aldol intermediate (Scheme 8.4) (see the chapter dealing with hetero-Diels-Alder reactions of carbonyl compounds). 

Fig. 8.13 Schematic representation of the change in energies for the concerted hetero-Diels-Alder reaction of benzaldehyde with Danishefsky s diene and the step-wise reaction...

The coupling photolysis Lewis acid is also sometimes effective in promoting a Diels-Alder reaction. Thus, cationic (R,S)-(ON)Ru-salen homochiral complex 71 catalyzed the Diels-Alder reaction between Danishefsky s diene and benzaldehyde when the reagents were exposed to direct sunlight through a window or to incandescent light in t-butyl methyl ether (TBME)[49] (Equation 4.8). The reaction in the dark was very slow and only 3 % ee was detected. 

Trifluoromethanesulfonic acid (triflic acid) in toluene greatly activates the Diels-Alder reaction of benzaldehydes with dimethylated 1,3-butadienes [89] (Table 4.22). With mono-methylated 1,3-butadienes the reaction gives less... 

The Hall group [52] has developed a new three-component domino reaction of 1-aza-4-borono-1,3-butadiene 4-152, a dienophile and an aldehyde to give a-hydroxy-methylpiperidine derivatives. In the first step, a hetero-Diels-Alder reaction takes place, which is followed by allylboration. As an example, reaction of 4-152 with the maleimide 4-153 in the presence of benzaldehyde furnished 4-154 in yields of up to 80% using the three substrates in a 1 2 1 ratio (Scheme 4.32). 

Asymmetric Diels-Alder reactions. Diels-Alder reactions of aldehydes with silyloxydienes catalyzed by this chiral organoaluminum compound can proceed with high enantioselectivity. Thus reaction of benzaldehyde with the silyloxydiene 2 at... 

Under the influence of 20 mol% of the chiral aluminum complex (S)-26, 2,3-dimethyl-1,3-butadiene adds to ethyl glyoxylate in dichloromethane at —78 °C to room temperature during 20 h to produce a mixture of the cycloadduct 23 (R2 = Et) (73% yield, 97% ee) and the ene product 24 (R2 = Et) (9% yield, 88% ee)17. The analogous aluminum complexes (R)-27 and (S)-27 (Ar = Ph or 3,5-xylyl) (10 mol% in toluene) catalyze the Diels-Alder reaction of benzaldehyde with the diene 28 to give, after the addition of trifluoroacetic acid, the dihydropyrone 29 in 95% ee, accompanied by a small amount of the corresponding fraws-isomer (equation 19)18. 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

TADDOL-Promoted Enantioselective Hetero-Diels-Alder Reaction of Danishefsky s Diene with Benzaldehyde-Another Example for Catalysis by Cooperative Hydrogen Bonding... 

Yamamoto reported an aluminum complex-catalyzed asymmetric hetero Diels-Alder reaction (Scheme 9.19) [36]. Chiral ketone d-3-bromocamphor discriminates (R)-organoaluminum complex 34 from (S)-complex 34 by diastereoselective complexation, whereas the remaining (S)-isomer 34 catalyzes the enantioselective cycloaddition of an activated diene to benzaldehyde. 

Stereoselective synthesis of /1-amino esters via asymmetric aldol-type and aza-Diels-Alder reactions has been reviewed.81 Siliranes react cleanly with benzaldehyde to produce oxasilacyclopentanes—with inversion—under conditions of Bu OK catalysis enolizable aldehydes yield silyl enol ethers.82... 

The first report of the use of enantiomerically pure lanthanoid complexes as chiral Lewis acids for Diels-Alder-type reactions appeared in 1983.90 As shown in Figure 37, in the presence of (+)-Eu(hfc)3(tris(3-(heptafluoropropylhydroxy-methylene)-(+)-camphorato)europium(III)), usually utilized as a chiral shift reagent for NMR study, the hetero-Diels-Alder reaction of benzaldehyde (54) with compound 167 has been found to give 168 in 50% ee. 

Table 3 Results of Diels-Alder reaction between Danishefsky s diene and benzaldehyde catalyzed by 18, 19, and 20 and their comparison with Jacobsen s catalyst 14-Cr/Cl...

A better accessible chiral mediator is the (acyloxy)borane (CAB) 2-64 prepared in situ from a tartaric acid derivative and arylboronic acid at room temperature. Hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene 2-10 in the presence of 2-64 gave the corresponding pyrone after acidic work up with 52 - 95 % ee depending on R. The best results were obtained with R = 2,4,6-Me3Ph and 2,4,6-iPr3Ph. Similarly, with 2-60 the pyrone 2-61 with up to 97% ee was found [107]. 

Similarly, Keck [111] has used the Ti(0-i-Pr)4/BINOL complex (10 mol %) for the hetero Diels-Alder reaction of l-methoxy-3-trimethylsilyloxy-1,3-butadienes 2-10 and non-activated aldehydes. The lowest enantioselectivity was obtained with benzaldehyde and the best with phenylacetaldehyde and some aliphatic aldehydes to give the corresponding dihydropyrans with ee values ranging from 75 % up to 97%. 

The synthesis of BENZYL ISOCYANIDE from benzaldehyde via reductive amination with 5-aminotetrazole followed by oxidation of the resultant amine with sodium hypobromite provides a general method for the synthesis of isocyanides. The preparation of BIS(2,2,2-TRICHLOROETHYL) AZODICARBOXYLATE makes available an alternative to dimethyl azodicarboxylate that is not only more reactive in Diels-Alder reactions but whose ester groups can be removed under neutral conditions. 

Fig. 7 (a) Selection-amplification of porphyrin tetrameric boxes using olefin metathesis, (b) Structure of dynamers formed via reversible Diels-Alder reaction, (c) Generation of a DCL of (R) and (S) nitroaldols from five differently substituted benzaldehydes... 

A novel Mannich reaction between A -alkoxycarbonylpyrroles 739, formaldehyde, and primary amine hydrochlorides catalyzed by Y(OTf)3 gave a monoaminoalkylation product 741 some times in good yield (14-81%) in aqueous media (Scheme 146) <2001TL461>. When formaldehyde was replaced by acetaldehyde or benzaldehyde, no reaction occurred. There was no formation of the 2,7-diazabicyclo[2.2.1]hept-5-ene 740 (through the aza-Diels-Alder reaction of an N-protected pyrrole with an aldehyde and amine salts by catalysis with triflate). 

A domino process for the construction of a tetracyclic ring was achieved by the gold-catalyzed formation of an isobenzopyrylium derived from a phenylacetylene-based benzaldehyde. This was followed by reaction with electron-rich benzo[ ]furan as a dienophile in a Diels-Alder reaction with inverse electron demand (Equation 102) <2003AGE4399>. 

Hetero-Diels-Alder reactions have also been conducted with aldehydes (Scheme 10) <2003JOC2803>. The reaction is very sensitive to the substitution pattern on the aldehyde and on the phosphole. Reaction of 1-phenyl-3,4-dimethylphosphole with benzaldehyde or its ra-derivatives afforded the corresponding adducts 55 in quantitative yields (Scheme 10). An increase in the steric demands of the aldehydes or of the phosphole results in a dramatic decrease in the yield. For example, with 2,4,6-trimethylbenzaldehyde, no reaction takes place and only 30% conversion is observed with 2,6-dimethoxybenzaldehyde. Similarly, using the more sterically hindered 1-phenyl-2,3,4,5-tetraethylphosphole, no cycloadduct formation is observed with benzaldehyde. Note that with decanal, the yield reaches only 40%. The reaction affords a mixture of endo- and o o-phosphinites 55, the major component being the OT o-derivative. With /ra t-cinnamaldehyde, a mixture of adducts 56 and 57 was obtained (Scheme 10), showing that the 1-phosphadiene can react either via the C=0 or via the C=C moieties of a,/3-unsaturated aldehydes <2003JOC2803>. 

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