High-pressure Diels-Alder cycloaddition

Synthesis and high-pressure Diels-Alder cycloadditions of 6-methoxycarbonyl-3-oxo-2-azabicyclo[2.2.0]hex-5-ene [86]... 

Polysubstituted pyridines 312 can be prepared by a sequence involving an intramolecular thermal or high-pressure Diels-Alder cycloaddition of oximino dienophile 310,... 

Even though a Birch reduction to give the requisite dihydronaphthalene for the Plieninger indolization is obviously successful, it is not an attractive or general method for providing these dihydronaphthalenes. In 1995, Kerr combined a high-pressure Diels-Alder cycloaddition of quinone mono ketals with 1,3-butadienes to give cycloadducts that readily aromatize to 1,4-dihydronaphthalenes (Scheme 3,... 

In a cycloaddition reminiscent of the Moody indole synthesis (Chapter 54), Ko5evar and Kranjc effected the high-pressure Diels-Alder cycloaddition of 2/7-pyran-2-ones with (Z)-l-methoxy-l-en-3-yne to afford indoles after acid-cycUzation (Scheme 10, equation 1) [39]. In some cases the 2,2-dimethoxyethyl intermediates were formed, but these were transformed to indoles under the same acidic conditions. An intramolecular [4+2] cycloaddition between ynamides and conjugated enynes to indolines and indoles was featured by Danheiser and Dunetz (equation 2)... 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

Drawn from these examples it is apparent that controlling the chemose-lectivity in inter-intermolecular Heck-Diels-Alder reactions of two different alkenes can be tedious if the alkenes show comparable reactivities. Nevertheless, the stepwise approach was realized in several other cases. In a synthesis of a derivative of cephalostatin 1 containing a central benzene instead of the pyrazine ring, Winterfeldt et al. linked two steroidal systems by a Heck coupling and subsequently performed high pressure Diels-Alder reactions of the conjugated diene with electron-deficient alkynes [34], Another example, reported by Hayashi et al., involves a selective Heck reaction of a bromoglu-cal with ethylene or acrylic acid derivatives followed by cycloadditions with maleic anhydride or N-phenylmaleimide [35]. 

First, some high-pressure Diels-Alder reactions in the solid phase will be described in the following paragraphs. The main part of this chapter will be devoted to high-pressure multicomponent domino cycloaddition reactions in the liquid phase and on the sohd phase. 

Synthesis by Cycloaddition.—Further details have been given of high-pressure Diels-Alder addition of maleic anhydride to thiophen, and we note the formation of Diels-Alder adducts from 2//-thiopyran, of the dimer (132), and of the adduct (133). ... 

Iwase and Aoki reported a very efficient synthesis of 3- or 4-substitufed pyridines via high-pressure Diels-Alder reaction of oxazole 1. For example, 1 reacted with acrylonitrile at 1.1 Mpa to produce 3-cyanopyridine 1652 in 95% yield (Scheme 1.425). Kondrat eva and co-workers described cycloaddition reactions of 2-aminoox-azoles 1653 with maleimide (Scheme 1.425). The authors isolated several different... 

A convenient synthetic route to obtain these compounds is the thermal Diels Alder cycloaddition of 1 -methoxybutadiene (18b) with carbonyl compounds, but this route is limited to aldehydes activated by an electron-withdrawing substituent. Non-activated carbonyl compounds require drastic conditions or fail to react. Application of high pressure overcomes this limitation. 

Cycloalkenones and/or their derivatives can also behave as dienic partners in the Diels-Alder cycloaddition. It is well documented [41] that cyclic acetals, for example, can interconvert with ring-opened enol ether forms, in a reversible manner the latter compounds can then be trapped by various dienophiles. Thus dienes 119 and 120 reacted with [60]-fullerene (Ceo) at high pressure, affording highly thermally stable products [42] (Scheme 5.16). Ketones 123 and 124 could be directly obtained by cycloaddition of enol forms 121 and 122 of 2-cyclopen-ten-and 2-cyclohexen-l-one, respectively. 

High-pressure and thermally induced asymmetric Diels-Alder cycloadditions of heterosubstituted dienes to homochiral ot, -didehydro amino acid derivatives [82]... 

The reaction of furan with 2,5-dihydrothiophene-3,4-dicarboxylic anhydride is remarkable (Scheme 6.19). Furan is a poor diene and requires high pressure to affect cycloadditions [39]. On the other hand, high temperatures are forbidden because cycloaddition products derived from furan undergo cycloreversion under these conditions. In 5.0m LP-DE, the Diels-Alder reaction of furan with 2,5-dihydrothiophene-3,4-dicarboxylic anhydride proceeds at room temperature and atmospheric pressure in 9.5 h with 70 % yield and with the same diastereos-electivity found when the reaction is carried out under high pressure [40]. 

The classic example of a reaction that demands control of translational entropy is surely the Diels-Alder cycloaddition. It is accelerated by high pressure and by solutions 8 m in LiCl (Blokzijl and Engberts, 1994 Ciobanu and Matsumoto, 1997 Dell, 1997) and proceeds through an entropi-cally disfavoured, highly ordered transition state, showing large activation entropies in the range of -30 to -40 cal mol-1 K 1 (Sauer, 1966). 

M-substituted pyrroles 55 entered the Diels-Alder cycloaddition with 1-Me only under high pressure to give mixtures of endo- and exo-adducts 56 (the ratio was not determined) (Scheme 14) [301. 

Oximes of type XON=CW2 (X = Ts, Tf, Ac W = CN, COiEt) are of interest as cycloaddition partners in [4-1-2] cycloaddition reactions of dienes For example, addition of acetoxyimino Meldrum s acid to dienes at high pressure afforded tetrahy-dropyridine derivatives. Recently, such reactions were studied in detail by Renslo and Danheiser. Thus, Diels-Alder cycloaddition of oximinotosylate 292 with a variety of 1,3-dienes afforded tetrahydropyridines 293, which can be easily transformed to... 

The hetero-Diels-Alder reaction of activated butadienes with carbonyl compounds is a convenient method for the preparation of precursors of sugars. Up to three chiral centers are created simultaneously. The high-pressure [4 + 2]cycloaddition of l-methoxybuta-1,3-diene 32 to N-mono- and N,N-diprotected alaninals was investigated [42-45]. The Eu(fod)3-mediated reaction of 32 with alaninal 25 gave a mixture of four diastereoisomers, which was then subjected to acidic isomerization, leading to the thermodynamically more stable pair of adducts syn-33 and anti-34, with predominance of the latter isomer (Scheme 12). The N-monoprotected alaninals reacted with a moderate ryn-diastereoselectivity. This method was used in the synthesis of purpurosamines (see Sec. DI.C). 

While studies of reactions in supercritical fluids abound, only a few researchers have addressed the fundamental molecular effects that the supercritical fluid solvent has on the reactants and products that can enhance or depress reaction rates. A few measurements of reaction rate constants as a function of pressure do exist. For instance, Paulaitis and Alexander (1987) studied the Diels Alder cycloaddition reaction between maleic anhydride and isoprene in SCF CO2. They observed bimolecular rate constants that increased with increasing pressure above the critical point and finally at high pressures approached the rates observed in high pressure liquid solutions. Johnston and Haynes (1987) found the same trends in the... 

The first Diels-Alder reaction studied under high pressure was the dimerization of cyclopen-tadiene [751]. For recent, more detailed studies of the pressure-dependence of Diels-Alder cycloaddition reactions in solvents of different polarity, as well as discussions of the corresponding mechanistic aspects, see references [857, 874]. 

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