Double intramolecular Diels-Alder

Double intramolecular Diels-Alder reactions of a,/3-unsaturated hydrazones have been used to prepare 2,2 bipyridines (Scheme 55) <1999CC793, 2001J(P1)2183>. 

Bushby, N.. Moody, C.J., Riddick, D.A., and Waldron, I.R., Double intramolecular Diels-Alder reaction of a,P-unsaturated hydrazones. A new route to 2,2 -bipyridines, 7. Chem. Soc., Chem. Commun., 793, 1999. 

Heating 255 led to double intramolecular Diels-Alder reaction followed by aromatization to afford 2,2 -bipyridine 256. ... 

The allenyl moiety (2,3-aikadienyl system) in the carbonylation products is a reactive system and further reactions such as intramolecular Diels-Alder and ene reactions are possible by introducing another double bond at suitable positions of the starting 2-alkynyl carbonates. For example, the propargylic carbonate 33 which has l,8(or 1.9)-diene-3-yne system undergoes tandem carbonylation and intramolecular Diels-Alder reaction to afford the polycyclic compound 34 under mild conditions (60 C, 1 atm). The use of dppp as ligand is important. One of the double bonds of the allenyl ester behaves as part of the dieneflSj. 

A highly efficient construction of the steroidal skeleton 166 is reported by Kametani and coworkers111 in the intramolecular Diels-Alder reaction of the a, jS-unsaturated sulfone moiety of 165 (equation 117). Thus, when the sulfone 165 is heated in 1,2-dichlorobenzene for 6h, the steroidal compound 166 can be obtained in 62% yield. The compound 166 produces estrone (167) by elimination of benzenesulfinic acid and subsequent hydrogenation of the formed double bond. The stereoselectivity of the addition reflects a transition state in which the p-tosyl group occupies the exo position to minimize the steric repulsion between methyl and t-butoxy groups and the o-quinodimethane group as shown in equation 117. 

Pentacylic cage compounds 202 were synthesized through a double cycloaddition reaction to methylenecyclopropene 199, which involves an intermol-ecular 1,3-dipolar cycloaddition of 198 on the endo double bond to give 200 followed by an intramolecular Diels-Alder reaction between a benzylidenecyclo-propane moiety and an ene function (Table 19) [49],... 

Retro-Diels-Alder reactions can be used to regenerate dienes or alkenes from Diels-Alder protected cyclohexene derivatives under pyrolytic conditions144. Most of the synthetic utility of this reaction comes from releasing the alkene by diene-deprotection. However, tetralin undergoes cycloreversion via the retro-Diels-Alder pathway to generate o-quinodimethane under laser photolysis (equation 89)145. A precursor of lysergic acid has been obtained by deprotection of the conjugated double bond and intramolecular Diels Alder reaction (equation 90)146. 

In the [4 + 2] cycloadditions discussed so far, the enol ether double bond of alkoxyallenes is exclusively attacked by the heterodienes, resulting in products bearing the alkoxy group at C-6of the heterocycles. This regioselective behavior is expected for [4+2] cycloadditions with inverse electron demand considering the HOMO coefficients of methoxyallene 145 [100]. In contrast, all known intramolecular Diels-Alder reactions of allenyl ether intermediates occur at the terminal C=C bond [101], most probably because of geometric restrictions. 

With [2](l,9)anthraceno[2](2,5)furanophane (45) the reaction takes a different course. Here, the intramolecular Diels—Alder reaction in the primary adduct 136 does not take place with the activated, substituted double bond as in the case of 42 and [2.2](2,5)furanophane (43), whose reactions with 133 have also been investigated 66 b>, but with the deactivated double bond functioning as dienophile. Spectroscopic findings indicate the structure 137 for the 1 2 adduct obtained when an excess of 133 is employed. 

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. 

The first example illustrates how a 1,4-dehydroaromatic system with cyclohexane ring having two double bonds may be also disconnected according to a retro-Diels-Alder to give a diene and an acetylene as the dienophile [25]. The second example makes clear that even an aromatic double bond may be -in some instances-involved in a retrosynthetic pericyclic disconnection [26]. In the synthetic direction, the polycyclisation involves a conrotatory electrocyclic cyclobutene ring opening, (16 15) followed by an intramolecular Diels-Alder addition (see Scheme... 

Lycorine is the most abundant alkaloid in plants of the Amaryllidaceae. Several syntheses of racemic lycorine had been reported prior to our initiation of studies directed at an asymmetric synthesis of the unnatural enantiomer 64. 2 a common theme in all of the syntheses of ( )-lycorine has been the utilization of either an intermolecular or intramolecular Diels-Alder construction of the key C-ring of the alkaloid. This six-membered ring presents a rather formidable synthetic challenge because of the four contiguous stereogenic centers, the trans 1,2-diol moiety, and the juxtaposition of the aromatic substituent and the carbon-carbon double bond. 

The pyrone ring then acts as the dienophile in the intramolecular Diels-Alder cycloaddition, which was conducted in a microwave oven. The final step of this synthesis is a high-temperature ester pyrolysis to introduce the exocyclic double bond of longifolene. 

The intramolecular Diels-Alder methodology has been used in approaches to naturally occuring furan derivatives (93JCS(Pl)2395). For example, thermolysis of (311) gave the product (312) in almost quantitative yield by cyclization followed by isomerization of the exocyclic double bond to rearomatize the furan residue. The reaction proved to be highly stereoselective. 

In an ingenious application of the extrusion reaction, 1-alkenyl-1,3-dihydro-benzo[c]thiophene 2,2-dioxides have been thermolyzed the diene system so generated undergoes an intramolecular Diels-Alder reaction with the isolated double bond in the side chain (79HCA2017). An (E) configuration of the diene is necessary for this purpose (Scheme 233). The by-products are styrenes arising from the (Z)-isomer. The same approach has also been used to prepare a steroid derivative (Scheme 233) (80JOC1463). 

Using intramolecular Diels-Alder reactions, Lease and Shea130 have prepared a series of bridgehead olefins, which at the same time are bridgehead lactams with the nitrogen atom at the other bridgehead (30). In these, the C=C double bond and the amide bond are subject to the same kind of distortion. The distortions decrease in the series 30a-30c. 

The stereochemistry of the cycloadducts in intramolecular Diels-Alder reactions depends upon the different geometry of the possible transition states 37—40 whose nomenclature can be explained as follows The orientation with the chain connecting the diene and dienophile lying under or above the diene is called endo. The opposite means exo. E and Z mark the geometry of the diene double bond which is connected with the chain. Syn and anti describe the arrangement of the hydrogen atoms (or substituents) at the prestereogenic centers which are involved in the C-C bond formation.12... 

The diterpenoid (24) undergoes29 an unusual intramolecular Diels-Alder reaction to afford (25) in which the furan ring acts as a dienophile adding across the l(10),2(3)-double-bond isomer of the parent diterpenoid. The absolute stereochemistry of the trans-clerodane caryoptin (26) has been determined30 by conversion into a C-6 ketone and comparison of the o.r.d. and c.d. curves with those of similar derivatives obtained from clerodin. 

A separate study of the alkylations of 1 has been reported by Oppolzer and co-workers. The group has employed LDA, LiTMP, and n-C4Hs,Li to metalate 1. The resulting anion condenses with a variety of electrophiles (primary alkyl bromides, iodides, tosylates, disulfides, and acyl derivatives) to afford the corresponding monosubstituted derivatives in 30-95% yield. If the alkyl group contains a double bond in the 4- or 5-position, polycyclic compounds are prepared by thermal extrusion of SO2 followed by intramolecular Diels-Alder cyclization. 

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