Intramolecular Diels—Alder reactions Lewis acid

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). 

Carbene complexes which have an all-carbon tether between the diene and the dienophile react via intramolecular Diels-Alder reaction to give the corresponding bicyclic compound. The stereoselectivities of these reactions are comparable to those observed for the Lewis acid-catalysed reactions of the corresponding methyl esters and much higher than those of the thermal reactions of the methyl esters which are completely unselective. Moreover, the ris-sub-stituted complexes undergo endo-selective reactions where the corresponding reaction of the ester fails [109] (Scheme 61). 

LiBp4 a mild Lewis-acid for intramolecular Diels-Alder reactions [93]... 

The intramolecular Diels-Alder reaction of 78 was investigated during the synthesis of isoquinoline alkaloids [65ij. No reaction occurred when solid-phase conditions were used (Florosil in DCM and CaCli) or when a variety of Lewis acids were employed (SnCU, BF3, RAICI2, Ti(z — Pr)4-TiCl4). A 56 % yield of 79 was obtained by carrying out the cycloaddition in toluene in a sealed tube at 200 °C. jS-CD catalysis in water under milder conditions (Equation 4.11) improved the conversion to 84 %. 

Although Lewis acid-catalyzed-Diels-Alder reactions of enones are common, there are few reports on the catalysis of Diels-Alder reaction of nitroalkenes. The reaction of nitroalkenes with alkenes in the presence of Lewis acids undergoes a different course of reaction to give cyclic nitronates (see Section 8.3). Knochel reported an enhanced reactivity and selectivity of the intramolecular Diels-Alder reaction using silica gel as Lewis acid in hexane (Eq. 8.19).31... 

In the highly competitive arena surrounding the Pfizer compounds CP-263,114 and CP-225,917 (Figure 4.2), Nicolaou and co-workers employed a hydrozirconation—iodination sequence to produce vinyl iodide 4 [17]. Lithium—halogen exchange and subsequent conversion to enone 5 sets the stage for a Lewis acid assisted intramolecular Diels—Alder reaction affording polycyclic 6 as the major diastereomer (Scheme 4.3). 

Finally, intramolecular Diels-Alder reactions, catalyzed by Lewis acids <1999TL7215> or thermally induced <1997JOC2093>, were used to obtain cyano-substituted indolizidine derivatives (Scheme 6). 

Lewis acid catalysis usually substantially improves the stereoselectivity of intramolecular Diels-Alder reactions, just as it does in intermolecular cases. For example, the thermal cyclization of 1 at 160°C gives a 50 50 mixture of two stereoisomers, but the use of Et2AlCl as a catalyst permits the reaction to proceed at room temperature, and endo addition is favored by 8 l.69... 

Intramolecular Diels-Alder reactions of trienes. -10 The thermal cycli/ation of the (f ,L)-triene 1 afl ords trans- and ci.v-perhydroindcnes 2 and 3, with a slight preference for the former isomer. The reaction is markedly catalyzed by Lewis acids such as A1C13, C,II5A1C12, and TiCI4, and results in cyclization exclusively to the... 

Intramolecular Diels-Alder reaction (with high periselectivity and good yields) of conjugated carbodiimides, catalyzed by Lewis acids, affords a simple procedure for the construction of pyrido[2,3-h]indole and indolo[2,3-ft]quinoline ring systems (equation 176)631. This procedure is superior to the often mixed reactions that occur in the absence of the Lewis acid632-635. It is interesting to note that Lewis acids also improve yields and selectivity in intermolecular reactions of this type636. 

A chair conformation (lower in energy than a boat conformation) is required for the formation of the trans fused product. Lewis acid-promoted intramolecular Diels-Alder reaction proceeds at 0 °C in the presence of Et2AlCl leading to the trans-fvLSQd product. Presumably, there is not sufficient energy to achieve the boat conformation to form the cis fused product. 

Lewis acid catalysts have been used in this approach.225-236-238 There are also a number of examples of hetero intramolecular Diels-Alder reactions.225 238-241... 

After having developed a reliable route to the enantiopure carboxylic acid 4a, we next turned our attention to gain access to the enantiopure decalin fragment. One of the most efficient approaches to this structural motif is the intramolecular Diels-Alder reaction. The first systematic studies in the racemic series were performed by Roush and co-workers in 1981 (Roush and Hall 1981). Evans (Evans et al. 1984, 1988) and Oppolzer (Oppolzer and Dupuis 1985) showed that chiral auxiliaries in combination with strong Lewis acids allowed the generation of the endo adducts with excellent diastereoselectivities (Scheme 5). Recently, chiral Lewis acid catalysts were successfully used by Evans (Evans et al. 1999) and Corey (Zhou et al. 2003). 

Intramolecular Diels-Alder reactions. The Lewis acid-catalyzed intramolecular Diels-Alder reaction is useful for construction of cw-fused bicyclo[6.4.0]dodecanes. Thus... 

Intramolecular Diels-Alder reactions resulting in bridgehead alkenes usually require high reaction temperatures. Consequently catalysts that permit use of lower temperatures are useful. Of a number of Lewis acids studied, diethylaluminum chloride was found to be the most efficient for the intramolecular cycloaddition of the triene 7 to 8 at 21°. The... 

Diastereofacial-setective intramolecular Diels-Alder reactions. Trienecarbox-imides derived from ahiral oxazolidones undergo Lewis-acid-catalyzed intramolecular Diels-Alder reactions With high endo- and diastereofacial selectivity (endo/exo 100 1). 

One of the most effective approaches to implementing the Diels-Alder participation of 1-oxa-1,3-butadienes is through the use of an intramolecular [4 + 2] cycloaddition reaction.A select set of thermal and Lewis acid-catalyzed intramolecular cycloaddition reactions of unactivated and electron-rich alkenes with a,P-unsaturated aldehydes and ketones has been detailed. Two examples of the poorly matched intramolecular Diels-Alder reaction of an a,P-unsaturated aldehyde (4 ir component) with an a, 3-unsaturated amide (2ir component) have proven successful (190-160 °C) and may be attributed to the entropic assistance provided by the intramolecular reaction. These observations have been applied in... 

Lewis acid and other catalyzed intramolecular Diels-Alder reactions 519... 

Dienes are also amenable for activation by copper Lewis acids (Sch. 41) [79]. The intramolecular Diels-Alder reaction of 176 under thermal conditions gave all the possible isomers. In contrast, the Cu(I) promoted reaction gave the isomer 177 as a major product, with minor amounts of 180. Copper(II) Lewis acids were less efficient in the cycloaddition. It is also worth noting that the Lewis acid-catalyzed reaction proceeds at a much lower temperature. 

The copper catalyzed Diels-Alder reactions of a variety of dienes have been elegantly exploited by Evans as a key step in the synthesis of natural products (Sch. 49). The synthesis of tetrahydrocannabinol (219) [92] employs the acyclic diene 217 furan is used as a diene in the synthesis of shikimic acid (222) [93]. Although the methodology uses the very reactive catalyst 188, the reactions are still slow, suggesting that less reactive dienes require longer reaction times and higher temperatures for completion. A copper Lewis acid-mediated intramolecular Diels-Alder reaction has served as a key step in the total synthesis of isopulo upone [94]. 

The endo/exo ratio can vary a lot depending on reaction conditions and the substrates. The ratio increases in favor of the endo product when Lewis acids are used to accelerate the Diels-Alder reaction. Increased steric interactions can turn the tide in favor of the exo product. In intramolecular Diels-Alder reactions, the ratio depends more on conformational preferences than anything else, and either exo or endo products may be obtained predominantly, depending on the reaction conditions and the particular substrate. 

Furyl derivatives 76, with an allylether or allylamine-type linkage to a methylenecyclopropane framework, readily undergo high pressure-promoted intramolecular cycloaddition" to give spirocyclopropane tricyclic products 77. No cycloaddition reaction occurred at ambient pressure and the products were mostly tar and polymers. Lewis acid catalysis was only marginally successful (Scheme 7.18). At 1.0 GPa and a slightly elevated temperature (60-70 °C) the intramolecular Diels-Alder reaction occurs readily and is exo-diastereo-selective. To quantify the pressure effect on the kinetics the volumes of activation were determined. 

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