Diels-Alder reactions consecutive

In addition to conventional Diels-Alder reactions, consecutive [4-1-2] reactions have been subjected to extensive investigation through the iminium-enamine catalytic sequence. Wang, Rios, and others simultaneously described enantioselective cascade sulfa-, oxa-, and aza-Michael/aldol/dehydration reactions promoted by chiral secondary amines. An initial strategy for a one-pot synthesis of chiral thiochromenes with good to high enantioselectivities was reported (Schemes 1.46 and 1.47) [71]. 

Polymerization. CPD dimerizes spontaneously and exothermically at ambient temperature to DCPD. At temperatures above 100°C, CPD can be made to polymerize noncatalytically via a series of consecutive Diels-Alder reactions to trimer, tetramers, and higher oligomers. Eor example, the trimers, 3a,4,4a,5,8,8a,9,9a-octahydro-4,9 5,8-dimethanobenz-lJT-[ iQdene, [7158-25-0] (3) and l,4,4a,4b,5,8,8a,9a-octahydro-l,4 5,8-dimethano-lJT-fluorene [35184-08-8] (4), are formed ia the ratio 87 13 by the monomer adding to the dimer (19). 

When the cnolate of an enone is brought into reaction with an enone, usually a carbocyclic system is prepared by two consecutive Michael additions (M1MIRC reactions). Due to the lower temperatures employed and the absence of diene polymerization these reactions are useful alternatives for Diels-Alder reactions and proceed in general with high diastereoselectivities. When neither enolate nor enone is cyclic a monocyclic system is formed 338 which can be converted into a bicyclic system when the Michael addition is followed by an aldol reaction339. When, however, the enolate is cyclic a bicyclic or a tricyclic system is formed340 341. 

To rapidly construct complex structures, a recent synthetic strategy uses the Diels-Alder cycloaddition in sequence with another Diels-Alder reaction or with other reactions without isolating the intermediates (domino, tandem, cascade, consecutive, etc., reactions) [4-6]. Scheme 1.2 illustrates some examples. 

A consecutive or timed Diels Alder reaction is a one-pot process in which the first Diels-Alder does not promote the second, so it is necessary to change the experimental conditions or add reagents to allow the successive cycloadditions (Equations 1.31 [62] and 1.32 [63]). 

It becomes intriguing to inquire what leads to the observed contrasteric reactivity. Intensive studies to disclose the origin of Tt-facial selectivity examined various dienes having unsymmetrical 7t-plane, since their reactions potentially generate five or more consecutive stereocenters with one operation. In this chapter, we review the theories to disclose the origin of 7t-facial selectivity in Diels-Alder reactions of the substrates having unsymmetrical 7t-planes. Recent works are discussed. 

The synthesis of the macrocycles 43 (Scheme 9) is an example of repetitive, highly stereoselective Diels-Alder reaction between bis-dienes 41 and bis-dienophiles 42, containing all oxo or methano bridges syn to one another. The consecutive inter- and intramolecular Diels-Alder reactions only succeed at high pressure. Obviously, both reactions are accelerated by pressure. The macrocycles are of interest in supramolecular chemistry (host-guest chemistry) because of their well-defined cavities with different sizes depending on the arene spacer-units. 

Benzo[c]furans (isobenzofurans) are reactive molecules usually employed as reactive dienes in the synthesis of more complex molecules. In the synthesis of spiro compounds related to fredericamycin A, Kumar generated the trimethylsiloxytrimethylsilylbenzo[c]furan 125 from phthalide via two consecutive deprotonations and silylations of the resulting anions. Diels-Alder reaction of the isobenzofuran as shown below with a spiroenedione leads to the formation of an endo-exo mixtures that can be smoothly converted to the dihydroxydione <00IJC(B)738>. 

Tandem pericyclic processes offer the opportunity to synthesize complex highly substituted cyclic molecules in a completely stereocontrolled fashion in a few consecutive steps. As a consequence, tandem processes have been studied extensively. Some tandem processes involving Diels-Alder reactions have recently been reviewed38,40,107. 

Winkler and Kwak144 recently prepared tricyclic ester 221 from 215 by means of three consecutive Diels-Alder reactions with 216, 218 and 91b to give 217, 219 and 220, respectively, followed by cleavage of the triple adduct 221 from the resin (equation 61). The overall yield was almost three times higher than when the same reaction sequence was performed in solution, thereby demonstrating the efficiency of resin-bound reactions in this case. 

Cobalt, as its CpCo(CO)2 complex, has proven to be especially suited to catalyze [2 + 2 + 2] cycloadditions of two alkyne units with an alkyne or alkene. These cobalt-mediated [2 + 2 + 2] cycloaddition reactions have been studied in great detail by Vollhardt337. The generally accepted mechanism for these cobalt mediated cycloadditions, and similar transition metal mediated cycloadditions in general, has been depicted in equation 166. Consecutive co-ordination of two triple bonds to CpCo(CO)2 with concomitant extrusion of two molecules of carbon monoxide leads to intermediates 578 and 579 via monoalkyne complex 577. These react with another multiple bond to form intermediate 580. The conversion of 578 to 580 is said to be kinetically favored over that of 579 to 580. Because intermediates like 580 have never been isolated, it is still unclear whether the next step is a Diels-Alder reaction to form the final product or an insertion to form 581. The exact circumstances might determine which pathway is followed. 

A more versatile approach uses an inner-outer ring diene system such as compound 496, which reacted with iV-methylmaleimide in toluene at 145 °C in a sealed tube to give cycloadduct 497 in 91% yield <2004TL7255>. Similar procedures with different electrophiles have been reported by other workers who were able to combine consecutively the preparation of the inner-outer diene by RCM reaction (see Section 2.04.9.3) and the Diels-Alder reaction in a one-pot process, which gave increased yields in most cases for the polycyclic compounds when compared with the two-pot approach <2004S2665>. 

In the 1950s two very effective pesticides were launched and their names were Dieldrin and Aldrin. As you may guess they were made by the Diels-Alder reaction. Aldrin is derived from two consecutive Diels-Alder reactions. In the first, cyclopentadiene reacts with acetylene to give a simple symmetrical cage molecule norbomadiene ... 

An interesting sequence of two consecutive Heck-type cyclizations and a subsequent Diels-Alder addition was observed when the methoxycarbonyl-substituted 2-bromo-trideca-1,1 l-dien-6-yne ( /Z)-63 was treated with the typical palladium catalyst (Scheme 3-20) [172]. The cyclization of dienyne 63 at 80 °C gave two diastereomeric trienes ( /Z)-64. At higher temperature (130 °C), an intramolecular Diels-Alder reaction of only the ( J)-isomer ( )-64 occurred to give the tetracyclic 65, whereas (Z)-64 remained as such, probably due to steric interference of the methoxy group. 

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