Quinone methide, Diels-Alder reaction

The ortho-quinone methides are difficult to isolate due to their high reactivity, which leads to rapid Diels-Alder dimerization or trimerization (Fig. 7.26). At 150°C, a partial retro-Diels-Alder reaction of the trimer can occur to form ortho-quinone methide and bis(2-hydroxy-3,5-dimethylphenyl) ethane (dimer).51... 

Wang, H. Wang, Y. Han, K.-L. Peng, X.-J. A DFT study of Diels-Alder reactions of o-quinone methides and various substituted ethenes selectivity and reaction mechanism. J. Org. Chem. 2005, 70, 4910-4917. 

All attempts to trap a with dienophiles failed. However, a synthesis of the benzoquinolizidine 4 involves an intramolecular Diels-Alder reaction with an o-quinone methide imine b, generated from 3 by CsF.1... 

DFT theory at the B3LYP/6-31G(d,p) level was used to investigate the Diels-Alder reactions of o-quinone methides with various ethenes. Calculations show that solvent decreases the activation energy and increase the asynchronicity.116 The Diels-Alder reaction of ortho-quinone methides derived from 3//-1,2-benzoxathiole 2,3-dioxides with maleimides produces chroman 2,3-dicarboxylic acid derivatives.117... 

The quinone methide (11) derived from flavan by a retro-Diels-Alder reaction gives only a 4% yield of acridine when heated with aniline. However, the other products include the diphenylmethane (12) and the Mannich base (13) both of which yield the tricyclic compound upon pyrolysis (J.L. Asherson. 0. Bilgic and D.W. Young, J. chem. Soc. Perkin I, 1980, 522). 

Since the remarkable demonstration of the facility of an intramolecular Diels-Alder reaction (dimerization) of an o-quinone methide, generated by the oxidation of a substituted o-alkylphenol in the development of a biomimetic synthesis of carpanone [Eq. (44)],170... 

Intermolecular Diels-Alder Reactions of o-Quinone Methide Imines... 

Lower reaction temperatures favor the reversible formation of the Diels-Alder products, and higher reaction temperatures promote the irreversible ene reactions. Related observations of the competing or predominating intramolecular Diels-Alder reactions of a-cyano or a-acetyl a,/3-unsaturated esters have been reported in studies of the thermal and Lewis acid-promoted ene reaction (Table 7-II, entry 16).143 The complementary use of o-quinone methide intermediates in intra- as well as inter-molecular [4 + 2] cycloaddition reactions is discussed in the following section. 

Until recently, attempts to trap the unstable o-quinone methide imines generated by this fluoride-induced 1,4-elimination in inter-molecular Diels-Alder reactions with typical dienophiles were unsuccessful.388... 

May and coworkers proposed the plausible biosynthetic root to communesin A (70) shown in Fig. (12) (part 1) [50]. A quinone methide (75) derived from tryptamine and the related natural product, aurantioclavine (76), undergo a Diels-Alder reaction to form a polycyclic intermediate (77). This highly twisted lactam (77) should be easily cleaved by the residual primary amine to produce spiro lactam (78). Reduction of 78 and aminal closure afford a common intermediate (79) of communesins. Epoxidation and acylation of 79 afford 70. Expansion... 

The exclusive formation of a single diastereomer with a trans ring fusion in the intramolecular Diels-Alder reaction of the o-quinone methide is consistent with the cycloaddition reaction proceeding through a preferred exo transition state from a chair conformation possessing an equatorial methyl substituent. The similar preference for a chair-exo transition state in the intramolecular [4 -t- 2] cycloadditions of substituted a,/3-unsatu-rated carbonyl compounds and substituted o-quinodimethane has been observed. A variant of these observations utilizes the room temperature fluoride-induced 1,4-elimination of trimethylsilynol for the in situ generation of an o-quinone methide enroute to the total synthesis of (+)-or (-)-hexahydrocannabinols [Eq. (48)]. ... 

A Diels-Alder reaction features in two approaches to the cannabinoid nucleus. A quinone methide is postulated in the intramolecular HDA cyclisation of (30) to (31) <97CC1867>, whilst an oxazoline-Cu(lI) complex imparts high enantioselectivity to the formation of the Al-THC precursor (32) <97TL3193>. 

The o-quinone methide derived from 4-hydroxypyrid-2-one and citronellal undergoes an intramolecular Diels-Alder reaction to give the chroman (5) structurally related to the free radical scavenger pyridoxatin and the antiinsectan Leporin A (94TL531). 

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