Dienes domino reactions

In 1987, Vaultier and coworkers [27] developed a combination of a [4+2] cycloaddition of a bora-1,3-diene to provide an allylborane, which then reacts with an aldehyde to give a highly functionalized alcohol. The Lallemand group, as well as Hall and colleagues, has recently used this procedure. In an approach for the synthesis of the antifeedant natural product clerodin (4-83), Lallemand and coworkers performed a three-component domino reaction of 4-80, 4-81 and methyl acrylate to give 4-82 (Scheme 4.18) [28]. 

It is not quite clear which step takes place first - the Co-catalyzed [2+2+1] cycloaddition of the outer alkyne moiety, or the Diels-Alder reaction of the diene with the inner alkyne to form a 1,4-cyclohexadiene, which then undergoes a Pauson-Khand reaction with the remaining alkyne. Recently, it has been shown that a domino reaction can also be performed using 1 mol of a 1,7-diphenyl-1,6-diyne 6/4-20 and a 1,3-diene 6/4-21 in the presence of Co/C at 150 °C under 30 atm CO, to give the polycyclic compounds 6/4-22 as sole product (Scheme 6/4.7) [282]. 

Scheme 6/4.7. Co-catalyzed domino reactions of a 1,7-diyne with a 1,3-diene...

An interesting pericyclic-anionic-pericyclic domino reaction showing a high stereoselectivity is the cycloaddition-aldol-retro-ene process depicted in scheme 20.1581 The procedure presumably starts with a [4+2]-cycloaddition of diene 98 and S02 in presence of a Lewis acid. After opening of the formed adduct reaction with (Z)-silyl vinyl ether 99 leads to a mixture of alk-2-enesulfinic acids 101. It follows a retro-ene reaction which affords a 7 3 mixture of the products 102 and 103. The reaction described by Vogel et al is a nice example for the efficient generation of polypropionate chains with the stereoselective formation of three stereogenic centers and one (0-double bond in a three-component domino reaction in its strict definition. 

A domino reaction,in this case consisting of an inter- and an intramolecular Diels-Alder reaction, is a key step in the synthesis of the hydrocarbon pago-dane 30, reported by Prinzbach et al When the bA-diene 27 is treated with maleic anhydride 4, an initial intermolecular reaction leads to the intermediate product 28, which cannot be isolated, but rather reacts intramolecularly to give the pagodane precursor 29 ... 

Thiyl and selenyl radical-mediated domino reactions of dienes... 

Madsen and Hyldtoft proposed a novel zinc-mediated domino reaction to give functionalized dienes.267 Using a Barbier reaction, different approaches of interesting compounds have been reported vitamin D3 analogs, 1 bicy-... 

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). 

A substrate with several functionalities which undergo transformations individually in the same pot is not a domino reaction. Clearly, the preliminary formation of an intermediate such as a carbocation or a carbanion is not counted as a reaction step. On the other hand the formation of a diene by a retro-Diels-Alder reaction with a subsequent cycloaddition would be considered as a domino reaction. 

Pericyclic domino reactions of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 and dimethyl l,2,4,5-tetrazine-3,6-dicar-boxylate 150 with dienes offer convenient entries into azo cage compounds 156-160 under mild conditions (Scheme 42) <1997JPR623>. 

Domino cyclizations of various types of polyenynes offer powerful synthetic tools for efficient syntheses of polycyclic compounds. Among many possibilities, several representative patterns are cited here. A fully intramolecular version of a three-step domino reaction of 2-bromododeca-l,l l-dien-6-yne 184 and 2-bromotrideca-l,12-dien-7-yne 189 offers a useful synthetic method of the tricycles 188 and 191 with a central cyclohexa-1,3-diene moiety. In these compounds 184 and 189, an alkenyl bromide starter, an alkynyl relay, and an alkenyl terminator are all tethered as summarized by 184 in Scheme 3.14. The final step is facile 6- 7r-electrocyclization of 187 and 190 to give rise to 188 and 191 [61]. 

A phosphane-mediated domino reaction of suitable electron-poor dienes 143 with N-tosyUmines 144 using water both as a solvent and a hydrogen source was reported by Marinetti and coworkers [80] (Scheme 12.56). 

An excellent high-pressure domino reaction is shown by the four-component transformation of 2-methoxybuta-l,3-diene 172 with fS-nitrostyrene 174 and 2 equiv of N-phenyhnaleimide 173, as reported by Scheeren and coworkers (Scheme 12.71) [99]. The reaction was completed within 42 h at 15 kbar to give a mixture of the two diastereomeric nitroso acetals rac-175 and roc-176 in yields of 84%. The domino process consists of a [4+2]/[4+2]/[3- -2] cycloaddition and leads to the products 175/176 with the formation of six new bonds and eight stereogenic centers in good yield and high stereoselectivity just forming only the two diastereomers in a ratio of7 3. 

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