Aldehydes Diels-Alder reactions with

Danshefsky s diene [19] is the 1,3-butadiene with amethoxy group at the 1-position and a trimethylsiloxy group at the 3-position (Scheme 18). This diene and Lewis acids extended the scope of hetereo-Diels-Alder reactions with aldehydes [20], This diene reacts with virtually any aldehyde in the presence of Lewis acids whereas dienes usually react with only selected aldehydes bearing strongly electron accepting a-substituents. There are two (Diels-Alder and Mukaiyama aldol) reaction pathways (Scheme 18) identified for the Lewis acids catalyzed reactions of Danishefsky diene with aldehydes [21, 22]. The two pathways suggest that these reactions occur on the boundary between the delocahzation band (the pericyclic... 

Taguchi described a difluorodiene (Eq. 149) which underwent smooth hetero Diels-Alder reaction with aldehydes, but was extremely unreactive towards... 

Diels-Alder reactions with aldehydes.2 This catalyst is superior to zinc chloride3 for promoting [4 + 2]cycloaddition of aldehydes with l-alkoxy-3-trimethylsilyloxy-1,3-butadienes to form 2,3-dihydro-4//-pyrane-4-ones. The catalyst prepared from bornyl alcohol is somewhat more effective than similar catalysts from simple alcohols, and may be of value for asymmetric induction. 

Silyloxy-2-aldehydes can undergo hetero-Diels-Alder reaction with aldehydes to give useful heterocycles.350 A model reaction, H2C=C(OSiH3)-N=CH2 with formaldehyde, has been explored theoretically. Lewis acids such as boron trifluoride catalyse the reaction by coordinating to the aldehyde oxygen, making the aldehyde more electrophilic. Concerted and stepwise mechanisms for this process are considered. 

Synthesis of dicyano-2-methylene-but-3-enoates as novel dienes for aU-carbon-based asymmetric inverse-electron-demand Diels-Alder reactions with aldehydes was also developed [37]. 

The hetero-Diels-Alder reaction of aldehydes 12 with 2-azabutadienes 13 (Scheme 8.5) has been studied using high-level ab-initio multiconfigurational molecular orbital and density functionality calculation methods [28]. 

The Diels Alder reaction of aldehydes 74 with dienes 75 in the presence of chiral acyloxyborane (CAB) catalysts 76 provides enantioselectively chiral 4-dihydropyranones (Equation 3.22) after CF3CO2H treatment of the cycloadducts [74]. 

Scandium(lll) perfluorooctanesulfonate [Sc(OPf)3 a novel catalyst for the hetero-Diels-Alder reaction of aldehydes with non-activated dienes [108]... 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

Scheme 2.164. Domino Knoevenagel/hetero-Diels-Alder reaction with aromatic aldehydes...

Today, multi-parallel synthesis lies at the forefront of organic and medicinal chemistry, and plays a major role in lead discovery and lead optimization programs in the pharmaceutical industry. The first solid-phase domino reactions were developed by Tietze and coworkers [6] using a domino Knoevenagel/hetero-Diels-Alder and a domino Knoevenagel/ene protocol. Reaction of solid-phase bound 1,3-dicarbonyl compounds such as 10-22 with aldehydes and enol ethers in the presence of piperidinium acetate led to the 1-oxa-1,3-butadiene 10-23, which underwent an intermolecular hetero-Diels-Alder reaction with the enol ethers to give the resin-bound products 10-24. Solvolysis with NaOMe afforded the desired dihydro-pyranes, 10-25 with over 90 % purity. Ene reactions have also been performed in a similar manner [7]. 

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

Mg11 is often employed in stereoselective reactions. In hetero Diels-Alder reactions of aldehydes with Danishefsky s diene, Mg11 results in good acceleration and stereoselection, and 2,3-coproducts are obtained exclusively (Scheme 6).26 Milder Lewis acidity is necessary for obtaining higher yield and higher stereoselectivity in this reaction, which occurs through a cyclic transition state. 

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... 

The asymmetric hetero-Diels-Alder reaction of aldehydes with Danishefsky s diene catalyzed by Ti catalysts generated from a library of 13 chiral ligands or activators has also been reported (Scheme 8.18). The catalyst library contains 104 members. The Ti catalysts bearing L, L , L, and J are found to have a remarkable effect on both enantioselectivity (76.7-95.7% ee) and yield (63-100%). On the other hand, ligands bearing sterically demanding substituents at the 3,3 -positions are found to be detrimental to the reaction. The optimized catalysts, both L /Ti/L and L /Ti/L , are the most efficient for the reaction of a variety of aldehydes, including aromatic, olefinic, and aliphatic derivatives. 

Additionally, investigations into imidazolidinone catalysed Diels-Alder reactions (Schemes 2 and 6) [234] have shown that iminium ions of a,P-unsaturated aldehydes and ketones have lower activation barriers for the Diels-Alder reaction with cyclopentadiene than the parent compound (13 and 11 kCal mol", respectively). It was also noted that transition structures show the formation of the bonds is concerted but highly asynchronous. 

A.2.1. Asymmetric Diels-Alder Reactions with Unsaturated Aldehydes... 

Chiral NHCs formed adducts with aldehydes that underwent enantioselective oxo-diene Diels-Alder reactions with enones.98 The NHC only needed to be added at 0.5 mol% to achieve yields >70% and ees in the high 90s. ... 

Scheme 5.6. Diastereoselective domino-Knoevenagel-hetero-Diels—Alder reaction with chiral aliphatic aldehydes.

Diels-Alder reactions with electron-rich alkenes.1 Simple a,(i-unsaturated im-ines (1-aza-1,3-butadienes) do not undergo Diels-Alder reactions with dienophiles. In contrast, the N-phenylsulfonyl imines derived from an aldehyde or ketone undergo Diels-Alder reactions under forcing conditions with electron-rich dienophiles to... 

The photochemical generation of hydroxy-o-quinodimethanes from o-alkylbenz-aldehydes may be followed by a thermal Diels-Alder reaction with alkenes (Scheme 9.33) [54]. This reaction is effective in both intermolecular and intramolecular modes, and has been applied to the synthesis of various natural products [55],... 

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