This thesis focuses on methodology development using N-sulfinyl metallodienamines and metalloenamines derived from Davis-Ellman N-sulfinyl imines. The application of these methodologies toward the total syntheses of (+)-epiibogamine and (+)-chimonanthine is described. The vinylogous aldol reaction of N-sulfinyl metallodienamines was first reported in 2017 in the total synthesis of (−)-albocycline. However, the diastereoselectivity of this reaction was found to be incorrectly reported. Mosher ester analysis and HPLC analysis with a chiral column were employed to determine the dr. The vinylogous aldol reaction was optimized. Studies on the mechanisms affecting stereoselectivity revealed that stereochemical erosion occurred using SnCl4 combined with LiHMDS, but not with NaHMDS or KHMDS. A (Z)-metallodienamine with metal chelated transition state was proposed and supported by DFT calculations to rationalize the stereochemical course of the reaction. Iboga alkaloids have been historically used for anti-addictive properties and recently brought more attention as potential drug candidates for neurological disorders. However, the complex isoquinuclidine fused azapine scaffold of Iboga alkaloids are challenging to synthesize. To construct the key chiral 2-aminocyclohexene intermediate and isoquinuclidine ring more efficiently, three new methods were explored. These included the domino-Michael/Mannich annulation of N-sulfinyl metallodienamines, the Diels-Alder reaction of N-sulfinyl imines, and the three-component domino-Michael/Michael/Mannich (DM3) annulation of N-sulfinyl metalloenamines. The DM3 reaction provided the 1-amino-2,4-diester scaffold to access isoquinuclidine in high yield (84−94%) and excellent diastereoselectivity (up to >95:5 dr). Chiral N-sulfinyl silylenamines, were introduced to serve as a surrogate for poorly reacting N-sulfinyl aldimines in the DM3 reaction. This silyl-modified DM3 reaction enabled the shortest asymmetric total synthesis of (+)-epiibogamine in 7 steps. This isoquinuclidine intermediate would also provide access to (+)-dihydrocatharanthine and other Iboga alkaloids in future studies. Oxidative enolate coupling, via radical intermediates, was used to construct 1,4-dicarbonyl scaffold from the reaction between two enolate nucleophiles. An oxidative coupling of N-sulfinyl metalloenamines was discovered having the ability to construct vicinal quaternary stereocenters in high diastereoselectivity (16:1 dr). To showcase this new methodology, the synthesis of dimeric indole alkaloids, (+)-chimonanthine, was investigated. A new class of compounds, bis N-sulfinyl amidines, were prepared as the potential oxidative coupling monomers for the synthesis of (+)-chimonanthine in future studies. / Chemistry

The purpose of this investigation is to examine reactions of anions of oximes, oxime ethers and imines with acylating agents and other electrophiles. It is also an attempt to utilize the phenomenon of geometrical enantiomeric isomerism, in which absolute configuration is determined by double bond geometry, and the concept of regiospecific anion formation, also determined by double bond geometry, for stereospecific synthesis of tropinone derivatives.

Ce projet scientifique concerne le développement de nouvelles méthodes efficaces de fonctionnalisation d’imines par des procédés organocatalysés et photocatalysésDans un premier temps la réaction photocatalysée d’alkylation d’énamines en conditions douces à été étudiée. L’utilisation de photocatalyseurs sous forme de complexes organométalliques d’Iridium a permis de réaliser la double fonctionnalisation d’ènecarbamates, permettant ainsi d’obtenir des substituts d’imines hautement substitués. Ce procédé permet de s’affranchir de l’utilisation de métaux lourds et ne nécessite qu’une activation par la lumière visible pour fonctionner. Cette transformation radicalaire éco-compatible à par la suite été soumise à une étude mécanistique approfondie. Dans une deuxième partie, la réaction d’aza-Friedel-Crafts organocatalysée par des acides de Brønsted chiraux à été étudiée. Dans cette réaction, la bi-fonctionnalité des acides chiraux dérivés du BINOL a été exploitée. Elle permet l’addition énantiosélective d’une grande variété d’indoles substitués sur des acyl-pyrrolidinones générées in situ. Les composés synthétisés présentent des structures bioactives intéressantes notamment sur le système nerveux central.Enfin, la première réaction de Povarov asymétrique impliquant des amino-hétérocycles comme précurseurs de 2-azadiènes à été décrite. Cette étude s’appuie sur des travaux antérieurs du laboratoire et permet la synthèse des analogues hétérocycliques de tétrahydroquinoléines précédemment décrites. Le procédé met en jeu une séquence multicomposants réduction/Povarov catalysée par des acides phosphoriques chiraux et permet l’accès rapide à une large bibliothèque d’analogues. / The aim of this study is the development of new methodologies for imines functionalization by organocatalysed and photocatalysed processes.First, a photocatalysed alkylation reaction of enecarbamates have been described. The use of organometallic Iridium complexes allowed the double functionalization of enecarbamates leading to highly substituted imines surrogates. This process is a green alternative to the use of heavy metals and only needs visible light as an renewable energy source to proceed. This environment-friendly radical transformation has been submitted to mechanistic study.In a second part, an aza-Friedel-Crafts reaction organocatalysed by chiral Brønsted acid has been studied. The bi-fonctionnality of chiral phosphoric acids has been advantageously used to perform the Friedel-Crafts addition of various substituted indole to in situ generated acyl-iminium ions. The compounds obtained by this methodology are showing interesting biological activities on central nervous system. Finally, the first enantioselective Povarov reaction involving amino-heterocycles as 2-azadienes precursors has been reported. This reaction is based on previous lab reports and the synthesis of tetrahydroquinoline analogues has been described. The multicomponent reduction/Povarov reaction sequence catalyzed by chiral phosphoric acids derived gives a rapid access to a wide library of bioactives analogues.

Ce travail de thèse est consacré à la synthèse de composés azotés biologiquement actifs s’inspirant notamment d’une réaction biosynthétique. Dans un premier temps, nos travaux avaient pour but de développer une nouvelle voie d’accès aux acides alpha-aminés par une réaction d’isomérisation énantiosélective d’imines. Après différentes études préliminaires, les meilleurs précurseurs d’acides alphaaminés par cette méthode que nous ayons identifiés sont les alpha céto amides. L’isomérisation 1,3 d’une imine formée à partir d’un alpha céto amide et de la diphénylméthanamine à l’aide de différents alcoolates chiraux a été réalisée. L’utilisation de l’alcoolate dérivé de la (+)-N-méthylpseudoéphédrine, employé en quantité sub-stœchiométrique, a permis d’obtenir l’alpha amino amide correspondant avec un excès énantiomérique de 67%. Il reste encore à mettre au point des conditions opératoires satisfaisantes pour la conversion de cet adduit en acide alpha aminé. L’étude de l’isomérisation 1,3 d’imines nous a permis de mettre en évidence une réaction de déshydrogénation 1,4 permettant d’accéder de façon originale à des 2-azadiènes et nécessitant la présence d’oxygène. Ainsi, plusieurs 2-azadiènes non activés ont été préparés par traitement basique d’imines issues de la condensation d’acétophénones et de diphénylméthanamine sous atmosphère d’air. Dans une dernière partie, l’étude de l’addition conjuguée d’une oxazolidinone chirale sur des alkylidènemalonates de dialkyle a été réalisée dans le but de développer une méthode d’accès à des acides alpha aminés. Les conditions opératoires mises au point ont permis d’obtenir une excellente diastéréosélectivité à partir de la plupart des alkylidènemalonates de dialkyle. / This thesis work is devoted to the synthesis of biologically active nitrogen-containing compounds, particularly inspired by a biosynthetic reaction. Initially, our work aimed to develop a new pathway to a-amino acids using anenantioselective imine isomerization reaction. After various preliminary studies, the best precursors of a-amino acids that we have identified are a-keto amides. The 1,3isomerization of an imine formed from an a-keto amide and diphenylmethanamine using various chiral alkoxides was then conducted. The alkoxide derived from (+)-N-méthylpseudoéphédrine, employed in sub-stoichiometric quantities, allowed obtaining the corresponding a-amino amide with 67% enantiomeric excess. It still remains to develop satisfactory operating conditions for the conversion of this adduct to an a-amino acid.The study of the 1,3 isomerization of imines allowed us to bring to light a 1,4 dehydrogenation reaction, which allows an original access to 2-azadienes and which requires the presence of oxygen. Thus, several non-activated 2-azadienes have been prepared by basic treatment of imines derived from acetophenones anddiphenylmethanamine, under air atmosphere.In the last part, the study of the conjugate addition of a chiral oxazolidinone on dialkyl alkylidenemalonates was carried out, with the aim to develop a method of access to enantiopure b-amino acids. Reactions conditions developed allowed to obtain an excellent diastereoselectivity from most dialkyl alkylidenemalonates.

Nucleophilic additions are an important class of reactions in the preparation of several organic compounds. Metals facilitate nucleophilic additions in many cases. The present work Mechanistic Investigation of Metal Promoted Nucleophilic additions is an attempt to understand the mechanism of nucleophilic additions to imines and carbonyl compounds mediated by the transition metal complexes. Understanding the mechanism of metal promoted nucleophilic additions can facilitate the design and synthesis of more efficient catalysts. Chapter 1 provides a brief introduction to nucleophilic addition. A few named reactions that involve nucleophilic addition are described. An overview of the metal promoted nucleophilic addition reactions and their mechanisms are presented. A short note on the importance of understanding the mechanism of metal promoted nucleophilic addition is included. This section ends with the scope of the present work. Chapter 2 “Mechanistic Investigation of Titanium Mediated Reactions of Imines” deals with two reactions. The first reaction is the formation of reduced amines on reduction of imines. Amines and diamines are synthesized often from imines. A convenient route to such nitrogen containing compounds is through reduction of imines and through reductive coupling of imines respectively. Since both reactions occur in a parallel fashion, during the synthesis of diamines, amines are obtained as side products and vice versa. This problem is acute in the case of titanium based reducing agents. These reducing agents are called low valent titanium reagents because low valent titanium species are generated in situ either from titanium(IV) or titanium(III) reagents. There is no clear understanding of the nature of the low valent titanium involved in the reaction. To rectify this, a mechanistic understanding of this reaction is essential. An attempt was made to probe the mechanism of formation of amines using low valent titanium formed by using two different reducing agents namely phenylsilane and zinc. With the help of isotopic labelling studies, it was found that the mechanism of formation of an amine with phenylsilane involves a direct hydrogen transfer from phenylsilane to an imine. This was verified using deuterium labelled phenylsilane. With zinc, it follows a traditional titanacycle pathway which was verified by quenching with the deuterium oxide. A second reaction that has been probed is the alkylation of imines by Grignard reagents using chiral titanium complexes. Alkylation of imines is one of the suitable routes to prepare chiral amines. Alkylation of imines employing a Grignard reagent with Ti(OiPr)4 can proceed through two different pathways depending on the amount of the Grignard reagent used. Alkylation reaction with one equivalent of Grignard reagent can proceed through a Ti(IV) species and the alkylation reaction with two equivalents of the Grignard reagent can proceed through a Ti(II) species. The reaction proceeding through Ti(IV) is less wasteful as it only requires one equivalent of the Grignard reagent. The two pathways differ from each other in the nature of the transition state where the C-C bond is formed. To verify the favourable pathway, chiral titanium complexes were prepared and alkylation carried out. The alkylation results suggest that one equivalent of Grignard is sufficient to give good yields of the alkylated product and the reaction may proceed through a Ti(IV) promoted path. It was reported in the literature that at least three equivalents of Grignard reagent are required to get good yields of the alkylated product with zirconium complexes. This work suggests a greener alternate to alkylation of imines. Chapter 3 “Asymmetric Transfer Hydrogenation Reaction of Ketones in Water” deals with the synthesis of chiral ruthenium half-sandwich complexes employing a proline diamine ligand which has phenyl, ethyl, benzyl, or hydrogen as a substituent. These complexes were characterized by X-ray diffraction. In addition, all these complexes were obtained as single diastereoisomers. These complexes were used as catalysts for the reduction of a variety of ketones to chiral alcohols in water using sodium formate as a hydride source. Stoichiometric reaction between sodium formate and the catalysts showed the formation of hydride complexes as the active species. Based on the electronic effects observed, the key step is found to be a nucleophilic attack of hydride on the carbonyl carbon of ketones. In the transfer hydrogenation reaction with DCOONa, more of 1-phenylethanol- 1-2H1 was observed with all the ruthenium catalysts suggesting that the hydrogen from sodium formate is transformed into a metal hydride which is subsequently transferred to the ketones to form chiral alcohols. The catalysts were optimized with acetophenone as a model substrate. Only in the case of a catalyst which has a phenyl substituent, silver nitrate was found to enhance the formation of aqua complex which in turn resulted in good yields of the chiral alcohols. Among all the complexes studied, the catalyst bearing a phenyl group induces greatest enantioselectivity. It can also be recycled. Chapter 4 “On the Formation of a Ruthenium-PPh2H Complex Using 1- Phenylethane-1,2-diol” deals with the mechanism of formation of PPh2H from PPh2Cl. This unique transformation involves a ruthenium-cymene dimer, PPh2Cl and 1-phenylethane-1,2- diol. In the attempted synthesis of a ruthenium bisphosphinite complex, using the ruthenium-cymene dimer, chlorodiphenylphosphine and 1-phenylethane-1,2-diol, the formation of [Ru(η6-cymene)Cl2PPh2H] was observed in good yield. Formation of the expected ruthenium bisphosphinite complex was not observed. The reaction was carried out in the absence of 1-phenylethane-1,2-diol resulted in the formation of [Ru(η6- cymene)Cl2PPh2Cl] suggests that the diol acts as a reducing agent. To verify the source of hydrogen in the 1-phenylethane-1,2-diol, deuterated diols were prepared. The reactions with the deuterated diols revealed several interesting aspects of the formation of the Ru-PPh2H complex. Chapter 5 “Mechanistic Studies on the Diazo Transfer Reaction” deals with the synthesis of labelled azides and the labelled azidating reagent to probe the mechanism of the diazo transfer reaction. Azides are important precursors used for a variety of chemical transformations including the celebrated Cu(I) catalyzed click reaction. Azides are also used as protecting groups for amines as they can be conveniently reduced to amines. Azidation of amines usually yield azides, with retention of stereochemistry. There is a possibility that the azide formation can occur through the SNi mechanism with retention of configuration where nitrogen in the starting material will not be retained after forming an azide. The reaction was carried out with 13C and 15N labelled L-valine and L-isoleucine to probe this possibility. The resultant labelled azide has 15N retained in its position. This excluded the SNi pathway. To show where the nucleophilic amine group is attacking the azide, labelled imidazole-1¬sulfonyl azide was synthesized from NaN215N. Reactions were carried out with L-valine (labelled and unlabelled) in the presence of a metal catalyst and with unlabelled L-valine in the absence of catalyst. These results confirm the postulated pathways described in the literature.

The research described in this thesis is directed toward the efficient, enantioselective synthesis of chiral products that have useful functionality. This goal was pursued through catalytic asymmetric hydrogenation, a reaction class that selectively introduces one or two stereocenters into a molecule in an atom-efficient step. This reaction uses a small amount (often <1 mol%) of a chiral catalyst to impart stereoselectivity to the product formed. Though catalytic asymmetric hydrogenation is not a new reaction type, there remain many substrate classes for which it is ineffective. The present thesis describes efforts to extend the reaction to some of these substrates classes. Some of the products synthesized in these studies may eventually find use as building blocks for the production of chiral pharmaceuticals, agrochemicals, or flavouring or colouring agents. However, the primary and immediate aim of this thesis was to develop and demonstrate new catalysts that are rapid and effective in the asymmetric hydrogenation of a broad range of compounds. Paper I describes the design and construction of two new, related chiral iridium compounds that are catalysts for asymmetric hydrogenation. They each contain an N,P-donating phosphinooxazoline ligand that is held together by a rigid bicyclic unit. One of these iridium compounds catalyzed the asymmetric hydrogenation of acyclic aryl imines, often with very good enantioselectivities. This is particularly notable because acyclic imines are difficult to reduce with useful enantioselectivity. The second catalyst was useful for the asymmetric hydrogenation of two aryl olefins. In Paper II, the class of catalysts introduced into Paper I is expanded to include many more related compounds, and these are also applied to the asymmetric hydrogenation of prochiral imines and olefins. By studying a range of related catalysts that differ in a single attribute, we were able to probe how different parts of the catalyst affect the yield and selectivity of the hydrogenation reactions. Whereas iridium catalysts had been applied to the asymmetric hydrogenation of imines and largely unfunctionalized olefins prior to this work (with varied degrees of success), they had not been used to reduce fluoroolefins. Their hydrogenation, which is discussed in Paper III, was complicated by concomitant defluorination to yield non-halogenated alkanes. To combat this problem, several iridium-based hydrogenation catalysts were applied to the reaction. Two catalysts stood out for their ability to produce chiral fluoroalkanes in good enantioselectivity while minimizing the defluorination reaction, and one of these bore a phosphinooxazoline ligand of the type described in Papers I and II. Enol phosphinates are another class of olefins that had not previously been subjected to iridium-catalyzed asymmetric hydrogenation. They do, however, constitute an attractive substrate class, because the product chiral alkyl phosphinates can be transformed into chiral alcohols or chiral phosphines with no erosion of enantiopurity. Iridium complexes of the phosphinooxazoline ligands described in Papers I and II were extremely effective catalysts for the asymmetric hydrogenation of enol phosphinates. They produced alkyl phosphinates from di- and trisubstituted enol phosphinate, β-ketoester-derived enol phosphinates, and even purely alkyl-substituted enol phopshinates, in very high yields and enantioselectivities.

Esta tesis describe el estudio de la aplicación en síntesis de N-terc-butanosulfinil derivados de alquil, alquenil, homoalil y homopropargil aminas como intermedios para acceder a moléculas orgánicas de mayor complejidad. Por un lado, se ha estudiado la adición de compuestos organomagnesianos y organolíticos a N-terc-butanosulfinil iminas, y los distintos derivados de aminas que se obtienen como resultado se han usado como precursores de alcaloides pirrolodínicos y piperidínicos, así como para acceder a anillos tipo azepano. Por otro lado, también se presentan aplicaciones en síntesis de N-terc-butanosulfinil homoalil y homopropargil aminas, que pueden participar en reacciones de oxidación allílica y cicloadiciones [2+2+2], respectivamente, para dar lugar a compuestos polifuncionalizados, en el caso de los derivados de homoalil aminas, y derivados de 9-amino-9, 10-dihidrofenantrenos y 1,2,3,4-tetrahidroisoquinolinas, en el cado de los derivados de homopropargil aminas.

A determinação do excesso enantiomérico (ee) em compostos quirais por ressonância magnética nuclear (RMN) foi descoberta há mais de meio século por Raban e Mislow e permanece bastante atual e importante. Uma das formas de quantificar o ee consiste em formar diastereoisômeros através de agentes quirais de derivação (AQD). AQDs com a função aldeído tem sido amplamente usados na discriminação de aminas quirais devido a fácil formação de iminas em condições brandas. Existe uma preferência pelo uso de aldeídos cíclicos como AQD, uma vez que sua menor flexibilidade conformacional favorece a diferenciação dos derivados diastereoisoméricos. Até o momento, não havia estudos de AQD utilizando compostos acíclicos. Desta forma, o objetivo desse trabalho foi utilizar o terpeno acíclico (S)-citronelal como AQD para a determinação do excesso enantiomérico de aminas primárias, através da RMN de 1H e 13C. Inicialmente, nós conseguimos observar uma preferência por conformações dobradas do (S)-citronelal por NOE e pela comparação entre os deslocamentos químicos teóricos, obtidos a partir da otimização com a correção de dispersão D3, e experimentais de RMN de 1H. Em seguida, nossos resultados sugeriram que a causa do dobramento molecular do citronelal estaria baseada em interações de London e HOMO-LUMO. Após a análise conformacional do (S)-citronelal, nós reagimos este composto dentro do tubo de RMN (\"mix and shake\") com misturas racêmica e escalêmicas das aminas sec-butilamina, 1-(fenil)etanamina e anfetamina, do amino-álcool 2-aminobutan-1-ol e dos amino-ácidos metionina e fenilalanina. Em todos os casos foi possivel fazer a determinação do ee e da configuração absoluta com grande eficácia. Os resultados mostraram que a metila ligada ao centro estereogênico do (S)-citronelal é um sinal conveniente para se determinar o ee de aminas quirais por ser facilmente reconhecido no espectro, uma vez que esse sinal já faz parte do agente quiral de derivação e também por estar em uma região bastante blindada do espectro tanto no RMN de 1H como no de 13C. Com isso, a completa e minuciosa elucidação estrutural torna-se desnecessária. Posteriormente, as conformações das iminas formadas mostraram, através de estudos teórico e experimental (NOE), um dobramento molecular semelhante ao encontrado no citronelal. O motivo para esse efeito também se encontra nas interações de London e nas interações de orbitais moleculares adequadas. / The determination of enantiomeric excess (ee) in chiral compounds by nuclear magnetic resonance (NMR) was discovered more than half a century ago by Raban and Mislow and remains quite current and important. One of the ways of quantify the ee is to form diastereoisomers via chiral derivatizing agents (CDA). CDA with the aldehyde function has been widely used in discriminating chiral amines because of easy formation of the imines under mild conditions. There is a preference for the use of cyclic aldehydes as CDA since their lower conformational flexibility favors the differentiation of the diastereoisomeric derivatives. As far as we are aware, there were no studies of CDA using acylic compounds. Thus, the goal of this work was to use acylic terpene (S)-citronellal as CDA for the determination of the ee of primary amines, through 1H and 13C NMR. Initially, we observed the preference for a folded conformations of the (S)-citronellal by NOE and by comparing the theoretical chemical shifts obtained from the optimization with the D3 dispersion correction, and experimental 1H NMR. Next, our results suggested that the cause of the citronelal molecular folding could be attributed to London and HOMO-LUMO interactions. After the conformational analysis of the (S)-citronellal, we reacted this compound within the NMR tube (\"mix and shake\") with racemic and scalemic mixtures of the sec-butylamine, 1-(phenyl) ethanamine, amphetamine, 2-aminobutan-1-ol, methionine and phenylalanine. In all cases, it was possible to make the determination of the ee and absolute configuration with great effectiveness. The results showed that methyl group attached to the stereogenic center of the (S)-citronelal is a convenient signal to determine the ee of chiral amines, because it is easily recognized in the spectrum, since that signal is already part of the CDA and also for being in a fairly shielded region of the spectrum in both 1H and 13C NMR. With this, complete and rigorous structural elucidation becomes unnecessary. Subsequently, the conformations of the imines formed showed, by theoretical and experimental (NOE) studies, the same molecular folding similar to that found in citronellal. The reason for this effect is also found in the interactions of London and in the interactions of suitable molecular orbitals.

Neste trabalho é apresentada a síntese e a caracterização de cinco novas iminas derivadas de compostos do tipo 2-(2`-hidroxifenil)benzazóis, fluorescentes devido a um mecanismo de transferência protônica intramolecular no estado excitado (ESIPT). Estas iminas foram caracterizadas por espectroscopia de absorção na região do infravermelho (IV) e por espectroscopia de ressonância magnética nuclear de hidrogênio (1H-RMN) e apresentaram deslocamentos de Stokes compatíveis com compostos que sofrem o mecanismo de ESIPT. Os produtos apresentaram sensível variação do máximo de emissão de fluorescência devido à reação de protonação em meio ácido, o que permite seu uso como sensores ópticos de pH. Ensaios demonstraram que as iminas sintetizadas são sensíveis à presença de Ni2+ devido à reação de complexação com o metal, causando uma alteração do máximo de emissão de fluorescência. / The present work presents the synthesis and characterization of five new imines derived from 2-(2`-hydroxyphenyl)benzazole derivatives, fluorescent due to an excited state intramolecular proton transfer (ESIPT) mechanism. These imines were characterized by infrared absorption spectroscopy (IR) and by hydrogen-1 nuclear magnetic resonance spectroscopy (1H-NMR) and presented Stokes shifts compatible with ESIPT compounds. These products presented a considerable shift of the maximum fluorescence emission due to the protonation reaction in acid medium, which allows their use as pH optical sensors. Tests showed that the synthesized imines are sensitive to Ni2+ due to the complexation reaction with the metal, causing a shift of the maximum fluorescence emission.

Mechanistic studies on three different ruthenium-based catalysts have been performed. The catalysts have in common that they have been employed in hydrogen transfer reactions involving alcohols and ketones, amines and imines or both. Bäckvall’s catalyst, η5-(Ph5C5)Ru(CO)2Cl, finds its application as racemization catalyst in dynamic kinetic resolution, where racemic alcohols are converted to enantiopure acetates in high yields. The mechanism of the racemization has been investigated and both alkoxide and alkoxyacyl intermediates have been characterized by NMR spectroscopy and in situ FT-IR measurements. The presence of acyl intermediates supports a mechanism via CO assistance. Substantial support for coordination of the substrate during the racemization cycle is provided, including exchange studies with both external and internal potential ketone traps. We also detected an unexpected alkoxycarbonyl complex from 5-hydroxy-1-hexene, which has the double bond coordinated to ruthenium. Shvo’s catalyst, [Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)] is a powerful catalyst for transfer hydrogenation as well as for dynamic kinetic resolution. The mechanism of this catalyst is still under debate, even though a great number of studies have been published during the past decade. In the present work, the mechanism of the reaction with imines has been investigated. Exchange studies with both an external and an internal amine as potential traps have been performed and the results can be explained by a stepwise inner-sphere mechanism. However, if there is e.g. a solvent cage effect, the results can also be explained by an outer-sphere mechanism. We have found that there is no cage effect in the reduction of a ketone containing a potential internal amine trap. If the mechanism is outer-sphere, an explanation as to why the solvent cage effect is much stronger in the case of imines than ketones is needed. Noyori’s catalyst, [p-(Me2CH)C6H4Me]RuH(NH2CHPhCHPhNSO2C6H4-p-CH3), has successfully been used to produce chiral alcohols and amines via transfer hydrogenation. The present study shows that the mechanism for the reduction of imines is different from that of ketones and aldehydes. Acidic activation of the imine was found necessary and an ionic mechanism was proposed.