Diels-Alder intramolecular

Firestone at al. " demonstrated the importance of solvent density in the special case of intramolecular Diels-Alder reaction in highly viscous media. Efficient packing of the hydrocarbon solvent was... 

Analogously, the effect of micelles on the rate of the unimolecular retro Diels-Alder reaction has been studied. Also here only a modest retardation" or acceleration" is observed. Likewise, the presence of micelles has been reported to have a modest influence on an intramolecular Diels-Alder reaction . Studies on the endo-exo selectivity of a number of different Diels-Alder reactions in micellar media lead to comparable conclusions. Endo-exo selectivities tend to be somewhat smaller in micellar solutions than in pure water, but still are appreciably larger than those in organic media In contrast, in microemulsions the endo-exo selectivity is reduced significantly" ... 

Revision Problem 3 House fJ. Org. Chem., 1965, 3 1061) wanted to study intramolecular Diels-Alder reactions and wanted molecules Uke TM 396 in which n is 3 or 4, so that the product will have a 5 or 6 membered ring if the reaction works. It would obviously be a good thing if the synthesis can easily be modified to make other size rings as well. What do you suggest ... 

To complete the story, when this molecule was heated an intramolecular Diels-Alder reaction did indeed take place to give a new fivemembered ring, (396A, n=3). 

As final examples, the intramolecular cyclopropane formation from cycloolefins with diazo groups (S.D. Burke, 1979), intramolecular cyclobutane formation by photochemical cycloaddition (p. 78, 297f., section 4.9), and intramolecular Diels-Alder reactions (p. 153f, 335ff.) are mentioned. The application of these three cycloaddition reactions has led to an enormous variety of exotic polycycles (E.J. Corey, 1967A). 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

The novel intramolecular reaction of the alkenyl bromide with the terminal alkyne in 328, followed by intramolecular Diels-Alder reaction, afforded the highly strained dynemicin A structure 329 in one stepf237]. 

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. 

An intramolecular Diels-Alder cyclization produces excellent yields of 2-aminoquinoline-3-carboxylate esters (57). Equally fine yields of the requited carbodiimides have been reported, making this an attractive route to an unusual substitution type. 

A similar intramolecular Diels-Alder strategy was employed in an efficient synthesis to an appropriately functionalized hydrindanone nucleus (212). After functionalization, Diels-Alder cyclization, and appropriate functional group manipulation, this hydrindanone was converted into ( )-cortisone. The overall process afforded ( )-cortisone in a total of 18 chemical steps in approximately 3% yield. 

Diisocyanoadociane, a novel marine-derived diterpenoid, was analyzed retrosynthetically using the intramolecular Diels-Alder transform as T-goal concurrently with topological and stereochemical guidance. The enantioselective synthesis outlined below allowed assignment of absolute configuration. 

Aqueous hydrofluoric acid dissolved in acetonitrile is a good catalyst for intramolecular Diels-Alder reactions [9] This reagent promotes highly stereoselective cyclizations of different triene esters (equation 8) The use of other acids, such as hydrochloric, acetic, and trifluoroacetic acid, results in complete polymerization of the starting trienes [9] (equation 8)... 

The di-r-butylsilylene group has been used to connect a diene and a dienophile to control the intramolecular Diels-Alder reaction. ... 

There are other Diels-Alder approaches to pyridines but they do not proceed in one step. For example, Weinreb reported the intramolecular Diels-Alder of oximino malonates tethered to a diene. Thermolysis of 102 produced 103 that upon treatment with base afforded pyridine 104. 

Reaction of 2-aminobenzyl alcohol with butenesulfonyl chloride gave 700 which upon treatment with BuLi followed by COCI2 gave the benzoxazine 701. Thermolysis of 701 in 1,2,4-trifluorobenzene gave the thiazoloquinoline 702 (96JCS(P1)1809) via an intramolecular Diels-Alder reaction (Scheme 121). 

Ab initio Hartree-Fock and density functional theory calculations were performed to study the transition state geometry in intramolecular Diels-Alder cycloaddition of azoalkenes 55 to give 2-substituted 3,4,4u,5,6,7-hexahydro-8//-pyrido[l,2-ft]pyridazin-8-ones 56 (01MI7). 

The intramolecular Diels-Alder reaction of 2-methyl-( , )-2,7,9-decatrienal catalyzed by the CBA catalyst 3 proceeds with the same high diastereo- and enantio-selectivity [5d] (Scheme 1.6). 

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). 

The chiral copper reagent 24 is an effective catalyst not only for intermolecular, hut also for intramolecular Diels-Alder reactions, as shown in the following schemes (Scheme 1.41, 1,42, 1.43). Synthetically useful octalin and decalin skeletons were synthesized in high enantio- and diastereoselectivity. The synthetic utility of this intramolecular Diels-Alder reaction has been demonstrated hy a short total synthesis of isopulo upone [23, 33d]. 

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). 

Table 1.25 Asymmetric intramolecular Diels-Alder reactions catalyzed by 31 [45 ...

Numerous examples of intramolecular Diels-Alder reactions have been repor-ted especially from application in the synthesis of natural products, where stereoselectivity is of particular importance e.g. syntheses of steroids. " ... 

A domino reaction,in this case consisting of an inter- and an intramolecular Diels-Alder reaction, is a key step in the synthesis of the hydrocarbon pago-dane 30, reported by Prinzbach et al When the bis-diQnQ 27 is treated with maleic anhydride 4, an initial intermolecular reaction leads to the intermediate product 28, which cannot be isolated, but rather reacts intramolecularly to give the pagodane precursor 29 ... 

DinitrQ-ll-Qxatricyclo[6 2 1 0 undec-9-ene has been prepared by an intramolecular Diels-Alder reacdon of the furan with a idtroalkene group as shown in Eq 8 26 This tricyclic compound is a versatile synthedc tool for the preparadon of ergot alkaloids... 

A first milestone was the development of a novel intramolecular Diels-Alder cyclizalion of terphenyl monomers 35 and 38 containing both 4-phenyIbutadienyI... 

In the event, treatment of a rapidly stirred solution of 3 and sodium acetate in MeOH-tbO at 38 °C with PdCl2 results in the fomation of carpanone (1) in 46% yield. The ordered unimolecular transition state for the oxidative coupling reaction furnishes putative bis(quinodimethide) 2 stereoselectively. Once formed, 2 readily participates in an intramolecular Diels-Alder reaction4 to give carpanone (1). Two new rings and all five contiguous stereocenters are created in this spectacular sequential transformation.5... 

Scheme 1. Inter- and intramolecular Diels-Alder reactions.

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