Heck-Diels-Alder

Another domino Heck/Diels-Alder process described by the same group [64] implies the Pd°-catalyzed reaction of 6/1-118 in the presence of acrylate or methyl vinyl ketone to give the corresponding bicyclic compounds 6/1-120 and 6/1-121 via the transient 6/1-119 (Scheme 6/1.32). Good yields were obtained only if potassium carbonate is used as base. 

Scheme 27. Domino Heck-Diels-Alder reaction and formation of dendralenes by cycloisomerization of enediynes...

Knoke and de Meijere [60] recently developed a highly flexible domino Heck-Diels-Alder reaction of a symmetrically substituted cumulene 125, which also involves cross-couplings of an allene at the central position. Both aryl and hetaryl halides react efficiently with l,3-dicyclopropyl-l,2-propadiene (125) and furnish 1,3,5-hexatriene derivatives 126 as intermediates, which are usually trapped by acceptor-substituted olefins in a subsequent cycloaddition, providing adducts 127a/b in moderate to good overall yields (Scheme 14.30). 

Domino Heck-Diels-Alder type reaction has been demonstrated by the reaction of l,3-dicydopropyl-l,2-propadiene with iodobenzene in the presence of dimethyl maleate under palladium catalysis (Scheme 16.28) [33]. 

Scheme 16.28 Domino Heck—Diels—Alder reaction.

Schemes . Domino Heck-Diels-Alder reactions of bicyclopropylidene (1) [147,148]...

Methyl 2-bromo-2-cyclopropylideneacetate (11a) has never been tested in these reactions, but has been used as a starting material for the stepwise construction of 1,6-heptadienes with methylenecyclopropane units for intramolecular Heck reactions. Thus, bromo ester 11a, after reduction, subsequent conversion of the resulting alcohol to the bromide and coupling with enolates of substituted malonates, was transformed into dienes of the type 254 (Scheme 73) - versatile synthetic blocks for the preparation of functionally substituted spirocyclopropanated bicyclo[4.3.0]nonenes 255a-d by a domino Heck-Diels-Alder reaction [122a]. 

Scheme 71. The application of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) in domino Heck-Diels-Alder chemistry [122,123]...

Scheme 8 Two-, three-, and fourfold donnino Heck-Diels-Alder reactions involving bicyclopropylidene 12 and nnethyl acrylate 1-C02Me. A Pd(OAc)2, PPhs, BU4NCI, K2CO3, MeCN, 80°C, 2 days. ...

In their pioneering work on the catalytic carbopalladation reaction of 1,2-heptadiene with phenyl iodide in the presence of a suitable base, Shimizu and Tsuji observed the formation of the corresponding substituted 1,3-dienes 62 via a / -hydride elimination from the 7z>allyl intermediate 61 [61]. Based on these observations, a three-component Heck-Diels-Alder cascade process has been developed by Grigg and co-workers [73]. A wide variety of aryl and heteroaryl iodides were used for the intermolecular reaction with dimethylallene to afford the corresponding 1,3-dienes. These subsequently react in situ with N-methylmaleimide to give the bicyclic adducts 63 (Scheme 8.30). 

When the carbopalladation of the bicyclopropylidene is performed in the presence of methyl acrylate, the reaction takes a different course (Scheme 8.34) [79]. The 1,3-diene intermediate 75 reacts in situ with the dienophile to give the spiro[2.5]octane derivative 76. An extension of this cascade Heck-Diels-Alder reaction involving l,3-dicyclopropyl-l,2-propadiene as the alkene partner, an alkenyl or aryl halide and a dienophile has been reported [80]. 

Scheme 2 Early examples of domino Heck-Diels-Alder reactions [19]...

These examples demonstrate that a selective Heck-Diels-Alder sequence with two different alkenes is only possible either in a stepwise manner, if an alkene reacts much faster in the Heck reaction than in the subsequent cycloaddition so that the 1,3-diene can be isolated, or as a real cascade reaction if one alkene is more reactive and thus selectively reacts as a coupling partner, whereas the other one is a better dienophile. Both concepts have been used by Kollar et al. for the annelation of cyclohexene rings onto the steroidal skeleton 26 (Scheme 4) [28-30]. At 60 °C the cycloaddition was sufficiently suppressed so that the Heck coupling product 29 could be isolated and subsequently subjected to Diels-Alder reactions with different dienophiles. For a domino reaction with both methyl acrylate and dimethyl fumarate (28) present in the reaction mixture, the conditions had to be precisely adjusted so that the mixed products 31 and 32 were formed predominantly along with only small amounts of the products of a twofold reaction of either 27 (R = CC Me) or 28 with 26. These conditions also proved suitable for a cascade reaction of 26 involving allyl alcohol 27 (R = CH2OH) or allyl acetate 27 (R = CH2OAc) and dimethyl fumarate (28). 

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]. 

Starting from suitably substituted 2-bromotrideca-l,ll-diene-6-ynes, an all-intramolecular domino Heck-Diels-Alder reaction can occur which features the formation of even four rings. When (E/Z)-125 is treated with... 

This is a general procedure for a domino Heck/Diels-Alder reaction [69] (Scheme 3-58). To a solution of diethyl allyl(2-bromoallyl)malonate (261) [257] (640 mg, 2.01 mmol) in acetonitrile (16 mL) in a screw-capped Pyrex bottle were added Pd(OAc)2 (14 mg, 3 mol%), PPh3 (42 mg, 8mol%), silver carbonate (665 mg, 2.41 mmol), and methyl 2-chloro-2-... 

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