Metal catalyzed ring expansion carbonylation, rearrangement, cyclization and oxidation reactions of nitrogen containing heterocyclic compounds.
Creators: name: Wang, Ming De.
Publisher: name: Université d'Ottawa / University of Ottawa
Year: 1993
Subjects: subject: Chemistry, Organic.

description: An important class of carbonylation reactions to construct lactams are those that involve the direct "stitching" of carbon monoxide into a nitrogen heterocycle resulting in ring expansion. Cobalt carbonyl catalyzed the carbonylation of a series of 2-substituted pyrrolidines to form piperidinones. The reaction is regiospecific in most cases and the yield of product is increased when ruthenium carbonyl is present as a second catalyst. Chapter 2 of this thesis describes this piece of work. During the investigation of the ring expansion carbonylation reactions of pyrrolidines, a new rearrangement process was discovered which occurred with nitrogen heterocyclic ketones $\rm\lbrack (CH\sb2)\sb{n}NCH\sb2COR,$ n = 4-7) to give lactams in 72-93% yields, catalyzed by the dual metallic $\rm\lbrack Co\sb2(CO)\sb8/Ru\sb3(CO)\sb \rbrack$ system. Studies, including several labelling experiments, indicated a hydrogen-oxygen positional exchanging path. After rearrangement, Ru$\sb3$(CO)$\sb $ could be recovered, and no Ru-Co clusters was detected. The most probable explanation for this finding may be that some of the steps in the reaction pathway are catalyzed by ruthenium while others are more effectively catalyzed by cobalt complexes. This work is discussed in detail in Chapter 3. A novel cyclization reaction was also observed during mechanistic studies giving information on the rearrangement reaction. That is, when ketones in which only one of the hydrogen atoms at an $\alpha$-carbon atom of a nitrogen-containing heterocycle is replaced by an alkyl group (e.g. 2-methyl (or 2,6-dimethyl)piperidinyl ketones), the reaction afforded the bicyclic 5,6,7,8-tetrahydroindolizines in 72-94% yields. In contrast to the rearrangement process which requires both Co$\sb2$(CO)$\sb8$ and Ru$\sb3$(CO)$\sb $ as catalysts, Co$\sb2$(CO)$\sb8$ or Ru$\sb3$(CO)$\sb $ only could catalyze the cyclization reaction in high yields. These bicyclic products are well known precursors of many alkaloids. Reaction of 2-aryl-5,6,7,8-tetrahydroindolizines with singlet oxygen, whether generated under sensitized photoreaction conditions or by cobalt catalyzed oxidation under mild conditions, gave 2-aryl-8a-hydroxy-6,7,8,8a-tetrahydro-3(5H)indolizinones in 63-71% yield. Chapter 4 deals with these transformations. Under phase transfer catalysis conditions some five and six-membered nitrogen-containing heteroaromatics reacted with acetylcobalt tetracarbonyl, generated in situ from CO, CH$\sb3$I and dicobalt octacarbonyl. Isoxazoles or isothiazoles gave N-acylated 1-amino-2-alken-3-ones or thiones, i.e. ring-cleavage reductive acylation products. The highest stereoselectivity (Z/E: 10/1) of the acylation reaction was found in the case of 5-methylisoxazole. Under the same conditions phthalazine, quinoline and isoquinoline gave N-acylated dimers in low to moderate yields. The reactivity of several other nitrogen-containing heterocycles such as pyrazoles was also investigated and the results are summarized in Chapter 5.