Heterocyclic substrates, 1,3-dienes

Monocyclic 1,2,3-triazines 1 behave like other six-membered heterocycles as dienes in Diels-Alder reactions with inverse-electron demand. Substrates are electron-rich dienes and acetylenes. 11 103, 284-290 jn mosl caseSi the formation of the isolated products can be explained by an attack of the dienophile at N1 and C4 or N3 and C6 of 1. In a few cases, products were obtained, the formation of which had to be explained by an intermediate formation of an azacyclobutadiene (azete) or by an N2 and C5 attack.284,285... 

In addition to the preceding advances primarily associated with heterocyclic substrates, similar additions were observed with simple ALformyl substrates (Scheme 3-100). Moreover, terminal alkynes were effective substrates in additions to styrenes and 1,3-dienes. Based on this combination of recent developments, the nickel-catalyzed fiinctionalization of a variety of relatively unreactive C-H bonds has now been demonstrated. Given the range of substrates that participates, many other classes of reactions that involve nickel-catalyzed C-H fimctionalization are to be expected. The special role of the combined effect of nickel and Lewis acid cocatalysis has emerged as an important influence in this growing body of catalytic processes. 

Studies by Mori demonstrate that triethylsilane and dienals undergo reductive cyclization in the presence of bis(T] -cycloocta-l,5-diene)nickel(0) (2) and triphenylphosphine (1 2) to produce the silyl ether of cycloalkanols P l in this instance, y.b-misaturated products are obtained. However, if the reaction is carried out in the presence of cyclohexa-l,3-di-ene, an analogous reaction proceeds to give 8,e-unsaturated products. This effect is reported to be derived from selective diene hydrometalation followed by addition of the or-ganonickel intermediate to the tethered aldehyde. The reaction proceeds with five-, six-, and seven-membered ring formation and with heterocyclic substrates. Several synthetic applications of this cyclization methodology are reported (Scheme 8). Intermolecular processes with simple dienes and aldehydes to afford y.S-unsaturated silyl ethers are also possible. 

Substrates for Diene Photooxygenation Carbocyclic Substrates Heterocyclic Substrates . . 25-3... 

Other advances include the construction of seven- and nine-membered rings via the analogous [4-1-3] and [6-1-3] cycloadditions with dienes and trienes respectively. Heterocycles, such as tetrahydrofurans and pyrrolidines, are accessible using carbonyl compounds and imines as substrates. The following discussion is organized around these recent discoveries. It serves to illustrate the versatility and the high degree of selectivity which are some of the distinctive features of the Pd-TMM chemistry. 

As the representative examples in Scheme 6.11 illustrate, similar stragies may be applied to the corresponding alkenyl ethers (vs. styrenyl ethers) [26], The Zr-catalyzed kinetic resolution/Ru-catalyzed metathesis protocol thus delivers optically pure 2-substituted di-hydrofurans that cannot be accessed by resolution of the five-membered ring heterocycles (see Scheme 6.8). It should be noted, however, that the efficiency of the Zr-catalyzed resolution is strongly dependent, and not in a predictable manner, not only on the presence but the substitution of the acyclic alkene site of the diene substrate. The examples shown in Scheme 6.11 clearly illustrate this issue. 

Abstract The basic principles of the oxidative carbonylation reaction together with its synthetic applications are reviewed. In the first section, an overview of oxidative carbonylation is presented, and the general mechanisms followed by different substrates (alkenes, dienes, allenes, alkynes, ketones, ketenes, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, phenols, amines) leading to a variety of carbonyl compounds are discussed. The second section is focused on processes catalyzed by Pdl2-based systems, and on their ability to promote different kind of oxidative carbonylations under mild conditions to afford important carbonyl derivatives with high selectivity and efficiency. In particular, the recent developments towards the one-step synthesis of new heterocyclic derivatives are described. 

The main types of substrates investigated so far are polycyclic aromatic compounds, aryl substituted carbo- and heterocyclic pentadienes, cyclic 1,3-dienes, furans, and olefins. It has turned out that type II photooxygenation of these compounds in solution occurs via the oxygen-activation mechanism. 

Metallacyclopentadienes undergo a range of synthetically versatile reactions which proceed with extrusion of the metal atom and attendant ligands. Thus, reactions with alkenes and alkynes afford cyclohexa-1,3-dienes and arenes (Scheme 6), and thiophenes, selena-cyclopentadienes, pyrroles and cyclopentadienones (indenones, fluorenones) can be obtained by treatment with sulfur, selenium, nitroso compounds and CO, respectively. The best studied substrates for such reactions are cobaltacyclopentadienes of the type (24a), which have been converted into a wide variety of arenes, cyclohexadienes and five-membered heterocycles, many of which would be very difficult to obtain by conventional organic procedures (74TL4549, 77JOM(139)169, 80JCS(P2)1344). 

Furthermore, the choice of enyne substrates can lead to cyclized products that contain other functionalities than dienes. Very recently, Muller and Kressierer [148] have shown that yne allyl alcohols 200 can be rapidly cyclo-isomerized by a Pd2dba3-W-acetyl phenyl alanine catalyst system to furnish heterocyclic enals 202 in excellent yields (Scheme 82). The intermediate product of the enyne cycloisomerization in this case is the enol 201, which rapidly tautomerizes to the aldehyde 202. 

A number of new Ni-catalyzed protocols have been developed recently for the coupling of carbonyl compounds and unsaturated substrates such as alkynes or 1,3-dienes. For instance, a three-component intramolecular coupling (alkyne/aldehyde/hydrosUane) has led to the formation of bicyclic N-heterocycles. A number of similar inter- and intramolecular coupling reactions have been developed into useful synthetic routes (Scheme 27). 

Complex 9 remains one of the most broadly applicable catalysts for this reaction, catalyzing hydroaminoalkylation with A -arylalkylamines, including controlled monoalkylation of dienes. This reactive catalyst 9 even displays tolerance of oxygen-containing substrates. Most importantly, this remains the only catalytic system capable of the direct C—H alkylation a to N of unprotected heterocyclic amine substrates. Such products are potentially important structural motifs for exploration in medicinal chemistry. In all cases this precatalyst shows regioselective hydroaminoalkylation to generate the branched product, and excellent diastereoselectivity when applicable (Scheme 20). [79]... 

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