Intramolecular Diels-Alder reactions double

Note that for 4.42, in which no intramolecular base catalysis is possible, the elimination side reaction is not observed. This result supports the mechanism suggested in Scheme 4.13. Moreover, at pH 2, where both amine groups of 4.44 are protonated, UV-vis measurements indicate that the elimination reaction is significantly retarded as compared to neutral conditions, where protonation is less extensive. Interestingy, addition of copper(II)nitrate also suppresses the elimination reaction to a significant extent. Unfortunately, elimination is still faster than the Diels-Alder reaction on the internal double bond of 4.44. 

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. 

Double intramolecular /zcfcro-Diels-Alder reaction of 1,3-diynil-bis-a,)S-unsaturated hydrazones 139 and 140 is a good example of a thermal multiple Diels-Alder reaction and is a particularly attractive route to annelated pyridines [123]. The initial cycloadduct readily aromatizes by the loss of dimethylamine (Scheme 2.52) under thermal reaction conditions. 

The chiral catalyst 142 achieves selectivities through a double effect of intramolecular hydrogen binding interaction and attractive tt-tt donor-acceptor interactions in the transition state by a hydroxy aromatic group [88]. The exceptional results of some Diels-Alder reactions of cyclopentadiene with substituted acroleins catalyzed by (R)-142 are reported in Table 4.21. High enantio- and exo selectivity were always obtained. The coordination of a proton to the 2-hydroxyphenyl group with an oxygen of the adjacent B-0 bond in the nonhelical transition state should play an important role both in the exo-endo approach and in the si-re face differentiation of dienophile. 

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],... 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

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 chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

A [3+3]-type annulation between a,a -dimethoxylated lactam 43 and allyltrimethylsilane gives bicyclic lactam 44. The reaction proceeds presumably through the allylation at the a-position followed by the intramolecular addition of the cation developed at the a -position to the allylic double bond (85JOC3243). The aza-Diels-Alder reaction of... 

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

Sheldrake and co-workers devised an elegant approach to interesting cage compounds based on an intramolecular hetero Diels-Alder reaction (88CC1482) (Scheme 51). The [4 + 2] cycloaddition of triazines 223 to 1,5-cyclooctadiene at M0°C resulted in the formation of 7-azatetracyclo[7.3.0.02 6.05 lo]dodec-7-ene derivatives 225 in 44-66% yield. The initial formation of 224 followed by the intramolecular cycloaddition of the electron-poor 2-azadiene moiety to the second carbon—carbon double bond of the cyclooctadiene system accounts well for the process. The dienophile unit can be placed just over the diene system favoring... 

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). 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

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... 

R. H. Martin, M. J. Marchant, Thermal Racemisation of Hepta-, Octa- and Nonahelicene Kinetic Results, Reaction Path and Experimental Proofs that the Racemisation of Hexa- and Heptaheli-cene Does Not Involve an Intramolecular Double Diels—Alder Reaction, Tetrahedron 1974, 30, 347-349. 

In search for control of absolute stereochemistry, the reaction of thio-chalcones was investigated with unsaturated amides bearing an Evans chiral oxazolidinone [223] and dimenthyl fumarate [224, 225]. For the first time with thiocarbonyl compounds, the efficiency of Lewis acid addition was demonstrated, and reactions could be conducted at room temperature. With EtAlCl2 (Table 4, entry 2) or A1C13 (entry 3), levels of induction up to 92% were attained for the endo isomer. Yb(OTf)3 in DMSO also caused the acceleration of the reaction with chiral acrylamides with p-facial selectivity [226]. This group has also reported [227] an intramolecular hetero Diels-Alder reaction with divinyl thioketones and the double bond of an allyloxy group (Table 4, entry 4). 

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