Diels-Alder reaction, intramolecular enantioselectivity

Brmsted acid-assisted chiral Lewis acid 8 was also applied to the intramolecular Diels-Alder reaction of an a-unsubstituted triene derivative. ( , )-2,7,9-Decatrienal reacts in the presence of 30 mol% of the catalyst to afford the bicyclo compound in high yield and good enantioselectivity [lOd] (Scheme 1.17). 

Application of this catalytic process was extended to asymmetric intramolecular Diels-Alder reactions. Synthetically useful intermediates with octalin and decalin skeletons were obtained in high optical purity by use of a catalytic amount of the chiral titanium reagent [45] (Scheme 1.57, Table 1.25). The core part of the mevi-nic acids was enantioselectively synthesized by use of this asymmetric intramolecular reaction [46] (Scheme 1.58). 

A new noncarbohydrate-based enantioselective approach to (—)-swainsonine was developed in which the key step was an aqueous intramolecular asymmetric hetero-Diels-Alder reaction of an acylni-troso diene (Eq. 12.57).128 Under aqueous conditions there was significant enhancement of the trans stereoselectivity relative to the reaction under conventional nonaqueous conditions. 

A combination of an enzymatic kinetic resolution and an intramolecular Diels-Alder has recently been described by Kita and coworkers [23]. In the first step of this domino process, the racemic alcohols ( )-8-55 are esterified in the presence of a Candida antarctica lipase (CALB) by using the functionalized alkenyl ester 8-56 to give (R)-8-57, which in the subsequent Diels-Alder reaction led to 8-58 in high enantioselectivity of 95 and 91 % ee, respectively and 81 % yield (Scheme 8.15). In-... 

An enantioselective synthesis of the Ziegler intermediate 107 of forskolin (108) has been achieved using an intramolecular allenic Diels-Alder reaction (Scheme 19.20) [24], Treatment of propargyl ether 104 with potassium tert-butoxide in tert-butanol affords 106, presumably through the intermediate allene 105. Compound 106 was obtained as a single stereoisomer. 

In a rather elegant approach towards colombiasin A (36) Flynn et al. [47] would access the tetracyclic carbon skeleton through an enantioselective intermolecular Diels-Alder sulfoxide elimination-intramolecular Diels-Alder (DA-E-IMDA) sequence between double-diene 166 and quinone 167 (Scheme 26). A key element of the proposed approach would be the chiral sulfoxy group in 167 which controls both the regio and facial selectivity of the intermolecular Diels-Alder reaction and eliminates generation of the dienophile for the IMDA reaction. 

Chiral catalysts (see Section 6.1.4) can also achieve enantioselectivity in intramolecular Diels-Alder reactions. 

Another enantioselective synthesis of longifolene, shown in Scheme 13.27, uses an intramolecular Diels-Alder reaction as a key step. The alcohol intermediate is resolved in sequence B by formation and separation of a menthyl carbonate. After oxidation, the pyrone ring is introduced by y addition of the ester enolate of methyl 3-methylbutenoate. 

Evans has utilized Cu(ll)-bis(oxazoline)-mediated Diels-Alder reactions as the key step in several total syntheses. In 1996, Evans and co-workers used bu-box ligand 3 in the intramolecular Diels-Alder reaction of oxazolidinone 87 to form cycloadduct 88 enantioselectively, as shown in Figure 9.31. Compound 88 was subsequently converted to (-)-isopulo upone 89. 

It is noteworthy that stereochemical control of the two new stereogenic centers at C4a and Cl2b ultimately stems from the stereochemistry at Cl through the intramolecular Diels-Alder reaction. Hence, an optically pure 46 should lead to an enantioselective preparation of a-epoxy lactone 48, thereby ultimately leading to an enantioselective synthesis of arisugacin A [1], LAH reduction of ( )-a-epoxy lactone 48 led to epoxy diol 49 in 78%... 

The non-selective thermal Diels-Alder reaction of hexa-2,4-dienol with methyl acrylate is made enantioselective by using the Lewis acid template (86) to assemble the reagents for cycloaddition.91 The Me2AlCl-catalysed intramolecular Diels-Alder... 

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... 

Asymmetric intramolecular Diels-Alder reaction.1 This chiral Ti catalyst system 4 is also effective for enantioselective intramolecular Diels-Alder reactions (equation I). In this particular case, a dithiane group accelerates the rate and enhances the em/o-selectivity, and is comparable to the gem-dialkyl effect. 

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 enantioselective hetero Diels-Alder reaction of 1-oxa-1,3-butadienes using chiral non-racemic Lewis acids is a widely unexplored field. The first successful example was the intramolecular cycloaddition of the heterodiene 2-194,... 

As a current example of a stereoselective intramolecular Diels-Alder reaction using nitroso dienophiles, Kibayashi s studies aimed at the enantioselective total sysnthesis of (-)-pumiliotoxin C 4-31 shall be discussed here [356, 357]. The chiral nitroso compound 4-30 derived from L-malic acid was generated in situ... 

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... 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

The inter- and intramolecular Diels-Alder reactions of furans, and their applications to the synthesis of natural products as well as synthetic materials, were reviewed <1997T14179>. HfCU promoted the endo-seXccuve. inter-molecular Diels-Alder cycloadditions of furans with a,/3-unsaturated esters <2002AGE4079>. The cycloaddition between furan and methacrylate was also achieved under these conditions, providing, however the o-isomer as the major cycloadduct. A catalytic enantioselective Diels-Alder reaction between furan and acryloyl oxazolidinone to provide the < 46i-adduct in 97% ee was achieved by using the cationic bis(4-fer7-butyloxazoline)copper(ll) complex 55, as shown in Equation (41) <1997TL57>. 

Schuster proposed a triplex as a key intermediate for the inter- and intramolecular photo-Diels Alder reaction in nonpolar solvents in the presence of an electron accepting sensitizer [105-107]. This photoreaction can be applied to an enantioselective photo-Diels Alder reaction between 1,3-cyclohexadiene and propenylbenzene by the use of a chiral sensitizer (Scheme 32) [108]. 

The intramolecular Diels-Alder reaction of 2-methyl-( , )-2,7,9-decatrienal with CAB catalysis proceeds with high diastereo- and enantioselectivities. ... 

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