Catalytic reactions which involve the cleavage of an sp(3) C-H bond adjacent to a nitrogen atom in N-2-pyridynyl alkylamines are described. The use of Ru(3)(CO)(12) as the catalyst results in the addition of the sp(3) C-H bond across the alkene bond to give the coupling products. A variety of alkenes, including terminal, internal, and cyclic alkenes, can be used for the coupling reaction. The presence of directing groups, such as pyridine, pyrimidine, and an oxazoline ring, on the nitrogen of the amine is critical for a successful reaction. This result indicates the importance of the coordination of the nitrogen atom to the ruthenium catalyst. In addition, the nature of the substituents on the pyridine ring has a significant effect on the efficiency of the reaction. Thus, the substitution of an electron-withdrawing group on the pyridine ring as well as a substitution adjacent to the sp(2) nitrogen in the pyridine ring dramatically retards the reaction. Cyclic amines are more reactive than acyclic ones. The choice of solvent is also very important. Of the solvents examined, 2-propanol is the solvent of choice.

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The ruthenium-catalyzed intermolecular cyclocoupling of ketones (or aldehydes), alkenes (or alkynes), and CO, which leads to γ-butyrolactones, is described. The reaction represents the first example of the catalytic synthesis of heterocycles via an intermolecular carbonylative [2 + 2 + 1] cycloaddition. A wide variety of ketones, such as R-dicarbonyl compounds and N-heterocyclic ketones, can be used in this cycloaddition. The addition of phosphines is quite effective in reactions of R-dicarbonyl compounds. Of the phosphines examined, P(4-CF 3 C 6 H 4 ) 3 represents the additive of choice. Cyclic olefins, unpolarized terminal olefins, and internal alkynes can be successfully used in the synthesis of highly functionalized lactones. The introduction of a CF 3 group to the aromatic portion of an aromatic keto ester accelerates the reaction of the keto ester with ethylene, while the introduction of a MeO group enhances the rate of the reaction of N-heterocyclic ketones with ethylene. The rate of the reaction increases with increasing pressure of ethylene or a lower pressure of CO relative to the reaction of a keto ester. However, these pressure-rate relations are reversed for the reaction of an N-heterocyclic ketone with ethylene. Such differences can be rationalized by assuming that the rate-limiting step in the catalytic cycle is different for these reactions.

The reaction of imines which contain N-heterocycles or an ester group with alkenes or alkynes and carbon monoxide in the presence of a catalytic amount of a ruthenium carbonyl results in [2+2+1] cyclocoupling to give g-butyrolactams in good yields.A [2+2+1] cycloaddition represents one of the most direct and convenient strategies for the construction of fivemembered carbocyclic and heterocyclic carbonyl compounds from simple acyclic building blocks. 1 In particular, the Pauson-Khand reaction, in which an alkyne, an alkene, and carbon monoxide are assembled into cyclopentenones, mediated by Co 2 (CO) 8 (Scheme 1, a), has been a subject of great interest. 2[2+2+1] Cycloaddition approaches to the construction of five-membered carbonyl compounds Scheme 1It should be noted, however, that the application of the [2+2+1] cycloaddition to the synthesis of heterocycles, such as g-lactone and g-lactam derivatives (Scheme 1, b), has met with limited success. In 1996, Crowe and Buchwald independently reported on the cyclocarbonylation of olefinic aldehydes and ketones leading to bicyclic g-butyrolactones, mediated 3,4 or catalyzed 4 by a titanocene complex. Subsequently, we reported on the Ru 3 (CO) 12 -catalyzed cyclocarbonylation of yne-aldehydes 5 and yneimines 6 to give bicyclic g-lactones and g-lactams, respectively. In these cases, a C=X moiety (X = O, N) and an alkene or alkyne are incorporated in an intramolecular manner. Quite recently, we reported the first example of the intermolecular [2+2+1] cyclocoupling of ketones, olefins, and CO catalyzed by Ru 3 (CO) 12 , a reaction which leads to the formation of g-butyrolactones bearing carbonyl or N-heterocyclic groups at the g-position. 7 This finding prompted us to examine the possibility of using imines in place of ketones for the synthesis of g-lactams, which are of importance for use as pharmaceutical agents. 8 Herein, we wish to report that the intermolecular [2+2+1] cyclocoupling of imines, alkene or alkynes, and CO can be achieved catalytically, using Ru 3 (CO) 12 as the catalyst.We initially examined the reaction of an imine which contained a 2-pyridyl group, since it has been reported that such a group, when adjacent to a carbonyl group has an accelerating effect in the ketone cycloadditions. 7 We were pleased to observe that the reaction proceeded smoothly and efficiently. The reaction of imine 1a (1 mmol) with ethylene (3 atmospheres) at 5 atmospheres of CO in toluene (3 mL) in the presence of Ru 3 (CO) 12 (0.025 mmol) at 160°C for 20 hours furnished the expected g-lactam 2a in 97% isolated yield, based on 1a (eq 1). The yields were lower when a tert-butyl group (38%), or a benzyl group (57%), or a p-toluenesulfonyl group (0%) were used as the N-protecting groups of the imine moiety. The introduction of an additional 2-pyridyl group at the imino carbon (i.e. 1b) resulted in the formation of the corresponding g-lactam 2b in quantitative yield. Imine 1c (E-isomer only) also underwent cycloaddition to give lactam 2c in a good yield. In contrast, the use of benzo...

The direct carbonylation of C-H bonds in the benzene ring of N-phenylpyrazoles via catalysis by ruthenium or rhodium complexes is described. The reaction of N-phenylpyrazoles with carbon monoxide and ethylene in the presence of Ru(3)(CO)(12) or Rh(4)(CO)(12) resulted in the site-selective carbonylation of the ortho C-H bonds in the benzene ring to give the corresponding ethyl ketones. A variety of functional groups on the benzene ring can be tolerated. N-Phenylpyrazoles have higher reactivities than would be expected, based on the pK(a) values of the conjugate acid of pyrazole. The choice of solvent for this reaction is significant, and N, N-dimethylacetamide (DMA) gives the best result.