Intramolecular Diels-Alder review

Several reviews on intramolecular Diels-Alder reactions have appeared19-23. The products may be either fused (equation 18) or bridged (equation 19). The vast majority of reported examples of the reaction result in fused products bridged compounds are rarely observed and only in cases where the diene and dienophile are separated by ten or more... 

The forward reaction is extremely easy bevause of aromaticity recovery. These aspects of the intramolecular Diels-Alder reaction are generally very useful and able to provide polycyclic fused six-membered ring compounds which are otherwise difficult to realize. The controlling factors, geometry and mechanism of intramolecular Diels-Alder reactions have been comprehensively reviewed elsewhere i°4,106), and it is not our intention to discuss these in details. However, the synthetic utility of the reaction is demonstrated by the following examples107). 

Allenes as versatile synthons including Diels-Alder reactions and especially intramolecular cycloadditions of this type were reviewed by Aso and Kanematsu [338], In some cases of intramolecular Diels-Alder reactions of open-chain starting materials such as 340 [339], 342 [339] and similar acceptor-substituted allenes [156], the formation of two new six-membered rings seems to be favorable if possible (Scheme 7.48). The non-activated cumulated C=C bond of 340 takes part in the [4+ 2]-cycloaddition and hence the necessary reaction temperature is high. On the other hand, the progressive truncation of the tether and the electron deficiency of the allenic C=C bond involved give rise to a remarkable Diels-Alder reactivity of the sulfone 346 generated in situ from sulfoxide 345 [339]. 

Mur 207), has received renewed interest in recent years. A fine review covering the intermolecular asymmetric Diels-Alder reaction was compiled by Mori 208>. In this article the use of terpenes and carbohydrates as chiral auxiliaries is discussed no amino acid derivatives are mentioned in this context. A chiral a-hydroxycarboxylic acid derivative was also used to achieve an asymmetric Diels-Alder reaction 209). High asymmetric induction could be detected in the intramolecular Diels-Alder reaction of chiral molecules. 

The development of intramolecular Diels-Alder (IMDA) reactions for the synthesis of natural products (80CR63) and the facility with which substituted furans can be assembled have been reviewed 840R(32)1, 86CRV795, 87CSR187, 90SL186). Thus, IMDA product from the propargyl sulfone shown in Scheme 43 proceeds via the allene and was converted subsequently into the benzenoid sulfone under base catalysis (92CC735). 

D. F. Taber, Intramolecular Diels-Alder and Alder Ene Reactions, Springer Verlag, New York (1984) (review)... 

There is an excellent recent review on intramolecular dipolar cycloadditions.1 Reviews on mechanistic aspects of intermolecular 1,3-dipolar cycloadditions abound2 and a treatise on intramolecular Diels-Alder cycloadditions is available.3... 

Ab initio and density functional theoretical studies of the 4 + 2-cycloaddition of 2-azabutadiene with formaldehyde predict a concerted reaction that agrees well with experimental evidence.184 The azadiene A-plienyl-l-aza-2-cyanobuta-l,3-diene reacts with electron-rich, electron-poor, and neutral dipolarophiles under mild thermal conditions.185 5,6-Diliydro-4//-1,2-oxazines have been shown to be usefiil as synthon equivalents of 2-cyano-l-azabuta-1,3-dienes.186 The intramolecular Diels-Alder reaction of 1-aza-l,3-butadienes (106) can be activated by a 2-cyano substituent (Scheme 37).187 Stereoselectivity in the hetero-Diels-Alder reactions of heterobutadienes, nitrosoalkenes, and heterodienophiles has been extensively reviewed.188 The azadiene l-(f-butyldimethylsilyloxy)-l-azabuta-1,3 -diene (107) reacts with halobenzo-quinones, naphthoquinones, and A-phcnylmalcimidc to yield low to good yields of various pyridine heterocycles (108) (Scheme 38).189 The 4 + 2-cycloaddition of homophthalic anhydride with A-(cinnamylidcnc)tritylaminc produces the 3,4-adduct whereas with A -(cinnamylidcnc)bcnzylidinc the 1,2-adduct is produced.190... 

A review cataloging intramolecular Diels-Alder reactions as key steps in the total synthesis of natural products has been published.78 A key step in the total synthesis (g) of (+)-dihydrocompactin (66) is the intramolecular ionic Diels-Alder reaction of the trienone (63) to yield the (+)-compactin core compound (65) via the intermediate cyclic vinyloxocarbenium ion (64) (Scheme 17).79 The intramolecular Diels-Alder reaction of the Asp-Thr tethered compound (67) produced the cycloadduct (68) with high regio- and stereo-selectivity (Scheme 18).80 Mixed quantum and molec- (g) ular mechanics (QM/MM) combined with Monte Carlo simulations and free-energy perturbation (FEP) calculations have been used to show that macrophomate synthase... 

For an excellent review of intramolecular Diels-Alder reactions see ... 

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>. 

Its synthesis has been fully clarified211 . The quinol-ester 5 is the probable primary product. An intramolecular Diels Alder addition leads to 6 and dehydrogenation gives 7. Reduction with zinc/acetic affords the phenanthrol carbonic acid 8. Since these reactions as well as similar reactions using propiolic acid are reported in the literature2U), the experimental details shall not be repeated in this review. The results... 

The efficiency of the intramolecular Diels-Alder reactions of furan has been described in several reviews, including an excellent treatise by Lipshutz. Steric factors, rather than electronic or solvent effects, appear to have the greatest influence on the outcome of the cycloaddition [1,19,20]. Electronically-disfavored cycloadditions can be brought about by creative functional group modifications. Thus, an electron-deficient furan, such as one bearing an a-keto group, can be masked and induced to undergo cycloaddition, as shown in Eq.8 [21]. 

The N=C—C 0 system of a I-phenothiazinone undergoes an intramolecular Diels-Alder reaction [B-42, 2455, 3067a, 3880] with diethyl acetylenedicar-boxylate, but with tetracyanoethylene (reviews (3146, 3244]), a mixture of products is obtained. 

The Diels-Alder reaction with inverse electron demand has been one of the most intensively studied reactions of 1,2,4-triazines. In this reaction 1,2,4-triazines behave as electron-deficient dienes and react with electron-rich dienophiles to give, generally, pyridines (see Houben-Weyl, Vol. E7b, p 471 ff). [4 + 2] Cycloadditions of 1,2,4-triazines have been observed with alkenes, alkynes, strained double bonds, electron-rich double and triple bonds, but in a few cases also with electron-deficient alkynes C—N double and triple bonds can also be used as dienophiles. In addition to intermolecular Diels-Alder reactions, intramolecular [4 + 2] cycloaddition reactions of 1,2,4-triazines have also been studied and used for the synthesis of condensed heterocyclic systems. A review on the intermolecular Diels-Alder reaction was published by Boger and Weinreb 14 Sauer published a review on his studies in 1992,381 and E. C. Taylor published a summary of his own work on intramolecular Diels-Alder reactions in 1988.382... 

The most extensively studied reaction of 1,2,4-triazines is the Diels-Alder reaction with inverse electron demand, in which the triazines behave as reactive electron-deficient dienes. Electron-rich alkenes and acetylenes have been most often used as dienophiles but alkenes with strained double bonds and nitriles can also react. Besides intermolecular Diels-Alder reactions, which were discussed in detail in CHEC-I, intramolecular cycloadditions have been studied widely and used in the synthesis of condensed heterocyclic systems. A review on intermolecular Diels-Alder reactions was published by Roger and Weinreb in 1987 , Sauer published an account of his studies in 1992 <92BSB52l>, and a summary by Taylor of his own work on intramolecular Diels-Alder reactions was published in 1988 <88BSB599>. 

Extensive reviews have summarized101a b and compiled101 the results of many of the studies to date, and Table 10-XI summarizes representative inter- and intramolecular Diels-Alder reactions of 1,2,4,5-tetrazines with carbon dienophiles. Extensive investigations of the participation of electron-deficient 1,2,4,5-tetrazines in inverse electron demand Diels-Alder reactions with electron-rich heterodienophiles have been described, and much of this work is summarized in Table 10-X1I. 

Diels-Alder Reactions. - It is very apparent that the year under review marks a sizeable decline in new descriptions of this reaction, especially as its intramolecular variant. However it is also clear that the intramolecular Diels-Alder reaction is now accepted as a powerful and important synthetic strategy. Although not normally included in this section the remarkable one-step formation of 8-ring aromatic steroids from acyclic precursors, as shown in Scheme 12, deserves noting. The taxanes constitute a... 

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