Intramolecular Diels-Alder reactions IMDA

Another important application of the iminium catalysis concept has been the development of enantioselective Type I [15, 30] and Type II [15] intramolecular Diels-Alder reactions (IMDA). (For experimental details see Chapter 14.18.3). For these transformations, both catalysts 1 and 3 proved to be highly efficient, as demonstrated by both the short and effective preparation of the marine methabo-lite solanapyrone D via Type I IMDA (Scheme 3.4, top) and the development of an early example of an enantioselective, catalytic Type II IMDA reaction (Scheme 3.4, bottom) [35]. Importantly, cycloadducts incorporating ether and quaternary carbon functionalities could be efficiently produced. 

The first synthesis using an intramolecular Diels-Alder reaction (IMDA) as key step was Borch s intended (zh)-dendrobine synthesis, which culminated in the synthesis of ( )-4-ep/-dendrobine (193) (153,154). 

Mance and Jakopcic have recently described the intramolecular Diels-Alder reaction (IMDA) of the furanic tertiary amine 25 in benzene under microwave irradiation conditions in sealed vessels [57]. Irradiation for 5 min at 140 °C afforded IMDA product 26 in 46% yield with little decomposition. Under classical conditions, heating a benzene solution of the amine 25 at 80 °C for 72 h under a nitrogen atmosphere, produced the IMDA product 26 in lower yield (12%) (Scheme 11.7). 

The copper(II) catalyst has been applied to the intramolecular Diels-Alder reaction.The precursor (8.71) imdergoes an intramolecular Diels-Alder reaction (IMDA reaction) which proceeds with remarkable selectivity to give the product (8.72), which was subsequently converted into the marine toxin (—)-... 

With this first round of simplifications complete, the majority of the cyclic bulk appended to the central core of the target molecules has been successfully excised. Of course, what still remains within 15 is the challenging [4.3.1] bicyclic system endowed with the anti-Bredt bridgehead C—C double bond. While this latter motif does seem formidable, if it is viewed within the context of the smaller six-membered ring in which it resides, then a possible course of retrosynthetic action should immediately be suggested in the form of an intramolecular Diels—Alder reaction (IMDA). Accordingly, application of this transform to 15 would lead directly to a precursor such as 17. Although the power of the Diels—Alder reaction to create complicated polycyclic architectures is rarely paralleled,"... 

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]. 

Enyne metathesis can also be combined with an intramolecular Diels-Alder reaction (IMDA) in a domino manner [35]. Reaction of the dienes 172 with the terminal alkynes 173 in the presence of the phosphine-free catalyst 4 at reflux temperature yielded the carbobicyclic products 174 preferentially via an exo-(E)-anti or endo-(2)-anti transition state for the [4- -2]-cycloaddition step, respectively (Scheme 2.60) [35a[. 

Enantioselective intermolecular [2-F2-F2] cycloadditions of 1,6-diynes with a,fS-unsaturated carbonyl compounds are valuable methods for the synthesis of chiral cyclohexadienes in a single step [36]. The intramolecular Diels-Alder reaction (IMDA) is known to be a powerful strategy for the construction of complex multicyclic skeletons [37]. Tanaka reported an efficient enantioselective domino intermolecular [2-F2-F2]/IMDA cycioaddition reaction occurring between 1,6-diyne 106 and amide-linked 1,5-diene 107 bearing two sterically and/or electronically... 

Four-Component Synthesis of Pyrrolopyridines If a primary amine were used as an input, the three-component reaction shown in Scheme 15.10 would produce an oxazole bearing a secondary amine. In other words, the so-produced adduct 24 would contain both a diene (oxazole) and a nucleophilic site (amine). Therefore, a dienophile bearing an electrophihc center would pair perfectly with the dual reactivity of 24. In practice, if an activated a,P-unsaturated carboxylic acid derivative were introduced after the three-component reaction, a sequence of N-acylation/intramolecular Diels-Alder reaction (IMDA) might occur to produce the four-component adducts. 

Step [138], that is, an intramolecular Diels-Alder reaction (IMDA) of intermediate 249 bearing an appropriate diene and a methylene tetronate. Despite the poor diastereofacial selectivity of this step, and the low overall efficiency, Yoshii s inventive strategy remains a masterful application of stereoselection via intramolecular cyclization. 

The influence of solvents [64] and comparisons with catalysts of the diarylpro-linol series [65] were reported. For theoretical calculations on stereocontrol see Reference [66]. In addition, imidazolidin-4-one catalyzed cycloadditions have been used in several total syntheses of natural products. Intramolecular Diels-Alder reactions (IMDA) were reported as key steps in the synthesis of bicyclo-undecenes [67], amaminols [68], solanapyrones [69], telomerase inhibitor UCS1025A [70], englerin A [71], (-)-nor-platencin [72], and muironolide A [73]. In addition, asymmetric [3-1-2]-cycloadditions of azomethines were accomphshed in the presence of chiral imidazoUdinones [74]. Intermolecular cycloadditions of dihydropyridine 53 and acrolein catalyzed by imidazolidin-4-ones were reported. The chiral azabicyclo-octenol 54 was isolated as the important key intermediate in the total synthesis of lycopodium alkaloids [75] (e.g., ludduline) and oseltamivir (Scheme 4.19) [76]. 

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