Diels organocatalytic

Ramachary, D.B. Barbas, C.R III (2004) Towards Organo-Click Chemistry Development of Organocatalytic Multicomponent Reactions Through Combinations of Aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen Cycloaddition Reactions. Chemistry A European Journal, 10, 5323-5331. 

Recently, a first example of an organocatalytic asymmetric domino Knoevenagel/ Diels-Alder reaction was reported by Barbas and coworkers (Scheme 2.182) [409]. Spiro[5,5]undecane-l,5,9-triones of type 2-818/2-819 were obtained from comma-daily available 4-substituted-3-butene-2-ones 2-813, aldehydes 2-814, and Mel-drum s acid (2-801) in the presence of 20 mol% of the amino acid 2-815 with 80-95% ee and diastereoselectivity of dr> 12 1. 

Diels-Alder Reactions The organocatalytic Diels-Alder reaction of a,P-unsaturated carbonyl compounds can be performed either via iminium (see Section 11.3) or enamine catalysis. The first highly selective enamine-promoted cycloaddition reaction was reported by Jprgensen and coworkers, who developed an amine-catalyzed inverse-electron-demand hetero-Diels-Alder (HDA) reaction (Scheme ll.lOa). ... 

The focus of this review is to discuss the role of Cinchona alkaloids as Brpnsted bases in organocatalytic asymmetric reactions. Cinchona alkaloids are Lewis basic when the quinuclidine nitrogen initiates a nucleophilic attack to the substrate in asymmetric reactions such as the Baylis-Hillman (Fig. 3), P-lactone synthesis, asymmetric a-halogenation, alkylations, carbocyanation of ketones, and Diels-Alder reactions 30-39] (Fig. 4). 

Radi M, Bernardo V, Bechi B, Castagnolo D, Pagano M, Botta M (2009) Microwave-assisted organocatalytic multicomponent Knoevenagel/hetero Diels-Alder reaction for the synthesis of 2,3-dihydropyran 2,3-c pyrazoles. Tetrahedron Lett 50 6572-6575... 

A key step in the total synthesis of the marine metabolite (—)-solanopyrone D (161) is the enantioselective organocatalytic intramolecular Diels-Alder reaction of the trienal (158) to the decalin aldehyde (160) in the presence of the imidazolidinone catalyst (159) (Scheme 45).187 Protonated 1,2-diamino-1,2-diphenylethane has been... 

Ahrendt KA, Borths CJ, MacMillan DWC (2000) New strategies for organic catalysis The first highly enantioselective organocatalytic Diels-Alder reaction. J Am Chem Soc 122 4243-4244 Akiyama T (2004) Preparation of chiral Bronsted catalysts in asym. synthesis and asym. Mannich, aza-Diels-Alder reaction, hydrophosphorylation therewith. PCT Int Appl WO 200409675, 2004-11-11... 

Wilson RM, Jen WS, MacMillan DWC (2005) Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solana-pyrone D. J Am Chem Soc 127 11616-11617 Xie JH, Zhou ZT, Kong WL, Zhou QL (2007) Ru-catalyzed asymmetric hydrogenation of racemic aldehydes via dynamic kinetic resolution efficient synthesis of optically active primary alcohols. J Am Chem Soc 129 1868-1869... 

Enders D, Htittl MRM, Runsink J, Raabe G, Wendt B (2007b) Organocatalytic one pot asymmetric synthesis of functionalized tricyclic carbon skeletons via a triple cascade/Diels-Alder sequence. Angew Chem 119 471... 

MacMillan DWC, Ahrendt KA, Borths CJ (2000) New strategies for organic catalysis the first highly enantioselective organocatalytic diels-Alder reaction. J Am Chem Soc 122 4243-4244... 

More recently, a fluorous organocatalyst has been used to perform selective Diels-Alder reactions of dienes with oc,(3-unsaturated aldehydes in acetonitrile-water. The chiral fluorous imidazolidinone catalyst can be recovered using fluorous silica (80-90% recovery efficiency) and reused. Figure 7.10. Further organocatalytic reactions are presented later in this chapter. 

Other examples of asymmetric reactions involving organocatalysts are (i) Diels-Alder reactions, (ii) Michael reactions, (iii) Mannich reactions and (iv) Shi epoxida-tion and organocatalytic transfer hydrogenation. 

For reviews on the organocatalytic Diels-Alder reaction see (a) A. Berkessel and H. Groger, Asymmetric Organocatalysis, Wiley-VCH, Weinheim, 2005, 256.(b) A. Berkessel and H. Groger, Asymmetric Organocatalysis, Wiley-VCH, Weinheim, 2005, 256.(c) H. PeUisier, Tetrahedron, 2007, 63, 9267. 

The MacMillan group expanded the scope of their organocatalytic Diels— Alder cascade in 2013 to complete an elegant, highly efficient nine step enantioselective synthesis of (—)-vincorine (18). ... 

Various cycloaddition reactions can be efficiently catalysed by prolinol silyl ethers.Dienamines generated from a,(3-unsaturated aldehydes participated in the Diels-Alder reaction with quinones. Nitrolefins can also function as dienophiles in organocatalytic Diels-Alder reaction. Reyes, Vicario and coworkers found that unconjugated 2,5-dienals are more reactive substrates than the corresponding conjugated aldehydes (Scheme 8.35). The reaction proceeded with clean p,E-selectivity and the corresponding products were obtained in high diastereomeric and enantiomeric purities. 

Scheme 8.35 Organocatalytic Diels-Alder reaction of unconjugated 2,5-dienals.

The first organocatalytic intermolecular asymmetric aldol reaction was reported by List and coworkers in 2000 [23]. The aldol reaction between acetone and a variety of aldehydes was accomplished in excellent yields and high levels of e-nantioselectivity. For example, the aldol product of the coupling with o-butyral-dehyde was formed in 97 % yield and 96 % ee ((1), Scheme 4.10). The remarkable levels of selectivity sparked massive interest in the field of proUne-catalysed aldol, Michael and Mannich reactions. Later that year MacMillan reported a phenylalanine-derived catalyst (35) for the Diels-Alder reaction of a-P-unsaturated aldehydes with up to 94 % ee ((2), Scheme 4.10) [24]. Many further applications of... 

Scheme 4.10 Organocatalytic aldol (1) and Diels-Alder (2) reactions...

The organocatalytic transfer hydrogenation of cyclic enones has been also successfully achieved employing the imidazolidinone 12 [24], catalyst that also promotes enantioselective Diels-Alder reactions with cyclic enones [25]. The structure of the dihydropyridine reagent seems to have an important effect on the selectivity of the process since better enantioselectivities are observed when increasing the steric hindrance of the ester moiety 13 (Scheme 2.6). The reduction, which is performed with substoichiometric amounts of imidazolidinone 12 in ether at 0°C,... 

In 2005, MacMillan reported an enantioselective organocatalytic intramolecular Diels-Alder reaction (IMDA) of a,p-unsaturated aldehyde and diene, as well as the application in the asymmetric synthesis of solanapyrone D (6), Scheme 3.1 [5]. Later, Danishefsky and Christmann individually reported the total synthesis of UCS1025A (9) by coupling reaction with MacMillan aldehyde (8) [6]. The malim-ide analogue 10 of the telomerase inhibitor UCS1025A (9) was also prepared by Christmann et al. by modified MacMillan s conditions (10 mol% catalyst loading in nitromethane, affording 74% yield and >99% ee after a sequence of recrystallization and oxidation). Scheme 3.2 [7]. 

Later on, Christmann, et al. developed an organocatalytic intramolecular Diels-Alder reaction of a,P-unsaturated dialdehydes, providing the bicyclic systems (such as decalins 13), [8] (Scheme 3.3). The mechanism was assumed to undergo the vinylogous enamine activation [9], followed by a rapid IMDA reaction and subsequent 6-hydride elimination. On the other hand, the synthesis of the cytotoxic marine natural product amaminol B (16) was achieved by Christmann and his co-workers with the key step of the organocatalytic IMDA reaction of 14, Scheme 3.4 [10]. 

Alternatively, Koskinen and Selkala reported an organocatalytic intramolecular Diels-Alder reaction of triene aldehyde 17 for the preparation of bicyclo[4.3.0] nonanes 18, Scheme 3.5 [11],... 

Later in 2002, MacMillan reported the first organocatalytic enantioselective Diels-Alder reaction of dienes with a,P-unsaturated ketones 34, Scheme 3.10 [20]. 

Recently, Overman, et al. reported an organocatalytic Diels-Alder reaction of 2-acetoxy-1,3 -butadiene 40 and acrolein (28f) by MacMillan catalyst, ent-30-HOTf, Scheme 3.11 [21], It was noteworthy to use water-saturated nitromethane as the reaction solvent. The adduct 41 was transformed to a tetracycle with the skeleton of the ring A-D of daphnicyclidin-Type alkaloids (42). 

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