As reações de metatese assim como o desenvolvimento de complexos metal-carbeno (W, Mo, Ru) se tornaram amplamente conhecidos na química graças aos avanços que trouxeram. Na química orgânica, possibilitou a síntese de macrocíclos por meio da RCM e na química de polímeros a ROMP permitiu um alto grau de controle da polimerização além da alta reatividade dos catalisadores. Isso fez desta reação uma poderosa ferramenta no desenvolvimento de novos materias. A tentativa de combinar a processabilidade dos polímeros com as propriedades luminescentes de determinandos compostos tem sido tema de muitas pesquisas.O objetivo deste trabalho é derivatizar compostos luminescentes , como o complexo metálico [Ru(bpy)3] (PF6)2e a porfirina tetrakis-(pentafluorfenil)porfirina (TPPF20), com o monômero norborneno (NBE) para obtenção de monômeros lumiscentes passíveis de serem polimerizados via ROMP. Aqui será apresentado e discutido a síntese e a caracterização desses compostos partindo-se dos reagentes: ácido-5-norborneno-2carboxílico; etilenodiamina e o ácido-2,2\'-bipiridina-4,4\'-dicarboxílico, cis-[RuCl2(bpy)2] e a porfirina TPPF20. Os compostos foram sintetizados com rendimentos superiores a 60%, com exceção da obtenção da porfirina, e caracterizados por RMN - 1H e 13C; FTIR; UV-vis. Os estudos de copolimerização entre NEN (norborneno-etilenodiamina-norborneno), NBE-TPPF e [Ru(bpy)2(NBbpy)](PF6)2 foram feitos usando o catalisador de Grubbs segunda gereação. Os polímeros gerados foram caracterizados usando TG-FTIR e RMN-1H, as massas moleculares não puderam ser calculadas por GPC porém os estudos indicam obtenção de baixo peso molelcular. O material obtido foi testado como sensibilizador em vidro condutor ITO, porém não houve adsorção do composto necessitam algumas modificações no metalomonômero. / The metathesis reactions as well as the development of metal-carbene complexes (W, Mo, Ru) became widely known in chemistry thanks to advancements brought. In organic chemistry, it enabled the synthesis of macrocycle by RCM. Useful for the synthesis of natural products. In polymer chemistry, ROMP, allow a high degree of polymerization control. This made the ROMP reaction a powerful tool in the development of new materials. In attempt to combine the processability of polymers with luminescent properties of such compounds has been the subject of several researchs. The aim of this work is to synthesize luminescent compounds based on [Ru(bpy)3] (PF6)2 metal complex and on the porphyrin tetrakis-(pentafluorphenyl)porphyrin (TPPF20), funcionalized with pendant norbornene monomer (NBE) to obtain lumiscentes monomers which can undergo ROMP polymerization. Here will be discussed the synthesis and characterization of these compounds using as starting materials: 5-norbornene-2-carboxylic acid; ethylenediamine; 2,2\'-bipyridine-4,4\'dicarboxylic acid, cis-[RuCl2(bpy)2] and the porphyrin TPPF20. The compounds were synthesized with yields higher than 60%, with the exception of the porphyrin, and characterized by 1H and 13C-NMR; FTIR; UV-vis. Copolymerization reaction between NEN (Norbornene-Ethylenediamine-Norbornene), NBE-TPPFe [Ru(bpy)2(NBbpy)] (PF6)2 were performed using Grubbs second generation catalyst. Resultinf polymers were characterized by TG-FTIR and 1H-NMR, molecular weight could not be measured by GPC, since polymers were insoluble, but studies indicate low molelcular weight. The material obtained was tested as sensitizer in conductive glass ITO. The polymer didn\'t adsorb in to the ITO surface. Some changes in the compound molecular structure are required to improve adsorption.

As reações de metatese assim como o desenvolvimento de complexos metal-carbeno (W, Mo, Ru) se tornaram amplamente conhecidos na química graças aos avanços que trouxeram. Na química orgânica, possibilitou a síntese de macrocíclos por meio da RCM e na química de polímeros a ROMP permitiu um alto grau de controle da polimerização além da alta reatividade dos catalisadores. Isso fez desta reação uma poderosa ferramenta no desenvolvimento de novos materias. A tentativa de combinar a processabilidade dos polímeros com as propriedades luminescentes de determinandos compostos tem sido tema de muitas pesquisas.O objetivo deste trabalho é derivatizar compostos luminescentes , como o complexo metálico [Ru(bpy)3] (PF6)2e a porfirina tetrakis-(pentafluorfenil)porfirina (TPPF20), com o monômero norborneno (NBE) para obtenção de monômeros lumiscentes passíveis de serem polimerizados via ROMP. Aqui será apresentado e discutido a síntese e a caracterização desses compostos partindo-se dos reagentes: ácido-5-norborneno-2carboxílico; etilenodiamina e o ácido-2,2\'-bipiridina-4,4\'-dicarboxílico, cis-[RuCl2(bpy)2] e a porfirina TPPF20. Os compostos foram sintetizados com rendimentos superiores a 60%, com exceção da obtenção da porfirina, e caracterizados por RMN - 1H e 13C; FTIR; UV-vis. Os estudos de copolimerização entre NEN (norborneno-etilenodiamina-norborneno), NBE-TPPF e [Ru(bpy)2(NBbpy)](PF6)2 foram feitos usando o catalisador de Grubbs segunda gereação. Os polímeros gerados foram caracterizados usando TG-FTIR e RMN-1H, as massas moleculares não puderam ser calculadas por GPC porém os estudos indicam obtenção de baixo peso molelcular. O material obtido foi testado como sensibilizador em vidro condutor ITO, porém não houve adsorção do composto necessitam algumas modificações no metalomonômero. / The metathesis reactions as well as the development of metal-carbene complexes (W, Mo, Ru) became widely known in chemistry thanks to advancements brought. In organic chemistry, it enabled the synthesis of macrocycle by RCM. Useful for the synthesis of natural products. In polymer chemistry, ROMP, allow a high degree of polymerization control. This made the ROMP reaction a powerful tool in the development of new materials. In attempt to combine the processability of polymers with luminescent properties of such compounds has been the subject of several researchs. The aim of this work is to synthesize luminescent compounds based on [Ru(bpy)3] (PF6)2 metal complex and on the porphyrin tetrakis-(pentafluorphenyl)porphyrin (TPPF20), funcionalized with pendant norbornene monomer (NBE) to obtain lumiscentes monomers which can undergo ROMP polymerization. Here will be discussed the synthesis and characterization of these compounds using as starting materials: 5-norbornene-2-carboxylic acid; ethylenediamine; 2,2\'-bipyridine-4,4\'dicarboxylic acid, cis-[RuCl2(bpy)2] and the porphyrin TPPF20. The compounds were synthesized with yields higher than 60%, with the exception of the porphyrin, and characterized by 1H and 13C-NMR; FTIR; UV-vis. Copolymerization reaction between NEN (Norbornene-Ethylenediamine-Norbornene), NBE-TPPFe [Ru(bpy)2(NBbpy)] (PF6)2 were performed using Grubbs second generation catalyst. Resultinf polymers were characterized by TG-FTIR and 1H-NMR, molecular weight could not be measured by GPC, since polymers were insoluble, but studies indicate low molelcular weight. The material obtained was tested as sensitizer in conductive glass ITO. The polymer didn\'t adsorb in to the ITO surface. Some changes in the compound molecular structure are required to improve adsorption.

Les réactions de métathèse sont des méthodes performantes pour la création de doubles liaisons carbone-carbone et leurs popularités s’expliquent par l’accessibilité des catalyseurs nécessaires à celles-ci et par la facilité de mise en oeuvre de ces réactions. Elles ont par ailleurs trouvé de nombreuses applications dans la synthèse de molécules naturelles.Les aurisides A et B sont des molécules naturelles d’origine marine isolées du lièvre des mers Dolabella Auricularia en 1996. Ces macrolides présentent une activité cytotoxique intéressante contre des lignées de cellules cancéreuses HeLaS3 avec des valeurs d’IC50 de 0,17 et 1,2 μg/mLrespectivement.Nous avons dans un premier temps développé une voie d’accès au fragment C1-C9 des composés naturels en se basant sur la réaction de métathèse croisée des oléfines. Une étude sur le mode formation de la structure macrocylique par un processus séquentiel impliquant une réaction demétathèse cyclisante et une cétalisation transannulaire a ensuite été conduite sur des composés modèles permettant l’obtention de macrolactones analogues. Cette méthodologie a ensuite été appliquée à la synthèse stéréocontrôlée du squelette carboné des aurisides seulement dépourvu de sa chaîne latérale attaché sur l’atome de carbone C13.Enfin la réaction de métathèse croisée a également été exploitée dans un processus tandem avec celle d’hydrogénation pour la synthèse énantiosélective du 6-hydroxydodécanoate de pentadécyle,composant principal de l’huile essentiel Ylang-Ylang, et qui est également utilisé en médecine traditionnelle contre le choléra. / Metatheses are very useful synthetic tool for the formation of carbon-carbon bonds and their popularityis due to the facile access of the required catalyst for those reactions and also to the ease to performthem. So far, these reactions have found many for the total synthesis of natural products.The aurisides A and B are natural products and have been isolated from the sea hare Dolabella Auricularia in 1996. These macrolides have shown significant cytotoxicity with IC50 values againstHeLaS3 cervical cancer cells of 0.17 and 1.2 μg/mL respectively.We have first developed an access to the C1-C9 fragment of these compounds using the crossmetathesis reaction as a key step. A study for the formation of the macrocyclic core of the aurisides,using a sequential ring closing metathesis / transannular ketalization process was then developed. Thismethodology was first performed on unfonctionnalized substrates and allowed the synthesis ofmacrolactone analogs. It was then further applied on a stereocontrolled synthesis of the aurisideswithout the side chain attached on carbon C13.Finally, the cross metathesis reaction was also combined in a tandem process with a hydrogenation reaction for the enantioselective synthesis of pentadecyl-6-hydroxydodecanoate, the major componentof essantial oil Ylang-Ylang, and is also used in traditional medical treatment against cholera.

La formation de liaisons carbone-carbone est primordiale dans le domaine de la chimie organique. Parmi les nombreuses méthodes existantes, les réactions de métathèse des oléf ines et de chimie radicalaire constituent deux techniques de choix mais n'ont été que très rarement utilisées de façon concomitante en synthèse organique. Cette constatation a été le point de départ de ces travaux de thèse dont le but a alors été d'appliquer ces deux réactions à la synthèse de molécules aux possibles propriétés biologiques. Une première étude combinant les réactions de métathèse qu'elles soient croisées ou d'énynes, et de cyclisation de type radicalaire ou de Heck, a été menée et a permis l'obtention de molécules à forte valeur ajoutée : des sultames à six chaînons et une nouvelle famille de spiro-sultames. Une seconde étude a quant à elle utilisé pour la première fois de façon séquentielle et en un seul pot les réactions de photodéconjugaison et de métathèse cyclisante permettant d'aboutir à la synthèse de composés intéressants mais difficiles à préparer, à savoir des lactones α,β-insaturées possédant un groupement alkyle en position α. Un troisième sujet utilisant à la fois les réactions d'addition de Michael asymétrique organocatalysée et de cyclisation radicalaire induite par le diiodure de samarium a permis de synthétiser des cyclopentanols trisubstitués comportant trois stéréocentres contigus. Enfin, une approche synthétique vers la nhatrangine A, molécule naturelle possédant six centres stéréogènes, et la synthèse totale du (+)-guaymasol ont été réalisées / Carbon-carbon bond formation constitutes a crucial research field in organic chemistry. Among all existing methods, olefin metathesis and radical reactions are particularly attractive ones but were rarely used in a concomitant way. That was the starting point of this PhD work, whose aim was to apply these two reactions to the synthesis of molecules having a potential biological interest. The first topic which was taken up was the use of cross- or enyne metathesis combined with a radical or an Heck cyclization for the synthesis of very valuable compounds : sultams and their spirocyclic derivatives. The second subject allowed the synthesis of α,β-unsaturated lactones bearing an alkyl group at the α position by using for the first time, in a one-pot and sequential manner, photochemistry and ringclosing metathesis. The third study led to cyclopentanol derivatives bearing three contiguous stereocentres by associating organocatalysis and radical cyclization induced by the use of samarium diiodide. Last but not least, a synthetic approach to nhatrangin A, natural compound holding six stereocentres, and total synthesis of (+)-guaymasol were carried out

Chapter one; “(-)-Rhazinilam and (-)-Rhazinal: Alkaloids with Anti-mitotic Properties Derived from Kopsia teoi”, provides the background information behind the motives that initiated this research project. The plant alkaloid (-)-rhazinilam [(-)-1] and its naturally-occurring derivative (-)-rhazinal [(-)-13] both exhibit potent anti-mitotic activities and, as such, are interesting targets for total synthesis. Chapter one is a review of the literature regarding these two compounds and discusses the occurrence, proposed biosynthetic origins, structural elucidation and biological activites of compound (-)-1 and that of its analogues including alkaloid (-)-13. Previous total syntheses of these two compounds are then examined, concluding with the only reported total synthesis of compound (-)-13. Developed within the Banwell research group, this total synthesis produced the racemic modification of alkaloid (-)-13 due to a lack of any stereocontrol in the key intramolecular Michael addition step. This unprecedented key step, involving cyclisation of the C2 of pyrrole onto an N-tethered and ?,?-disubstituted acrylate to produce a quaternary-carbon stereogenic centre, would be of greatly enhanced utility if it could be achieved in a catalytic-enantioselective fashion. The realisation of this goal is the central aim of the research conducted within this thesis. ¶ Chapter two; “Investigating Asymmetric Induction in the Intramolecular Michael Addition of pyrrole to N-Tethered Acrylates and Related Species”, introduces the model study used to direct research towards achieving the goal of asymmetric induction in the title process. The model is a somewhat simplified version of the original process used in the total synthesis of compound (-)-13 involving cyclisation of the C2 of pyrrole onto an N-tethered and ?-monosubstituted Michael acceptor, to produce a tertiary-carbon stereogenic centre. This simplification allows the rapid synthesis of a broad range of potential substrates for use in the title process, thus enabling the investigation of various different approaches to inducing asymmetry therein. High levels of asymmetric induction are observed with the use of chiral substrates or catalysts, facilitating the synthesis of both 6- and 7-membered rings annulated to pyrrole with construction of the relevant tertiary-carbon stereogenic centre in enantio-enriched form. For the reactions producing a 6-membered ring annulated to pyrrole, unambiguous proof of the absolute sense of asymmetric induction observed in the intramolecular Michael addition event is established using a chemical correlation study involving elaboration of a key indolizine-type cyclisation product, to the plant alkaloid of known absolute stereochemistry, (-)-tashiromine [(-)-75]. For the reaction producing a 7-membered ring annulated to pyrrole, the same information is obtained via X-ray crystallographic analyses of a dibrominated derivative of a key pyrroloazepine-type cyclisation product. ¶ Chapter three “An Enantioselective Total Synthesis of the Alkaloid (-)-Rhazinal: An Anti-mitotic Agent Isolated from Kopsia teoi.”, focuses on the application of methodology developed in the previous chapter, to the original goal of inducing asymmetry in the intramolecular Michael addition reaction, involving cyclisation of the C2 of pyrrole onto an N-tethered and ?,?-disubstituted acrylate to produce a quaternary-carbon stereogenic centre. This is ultimately achieved in a catalytic-enantioselective fashion, resulting in the first such total synthesis of the anti-mitotic alkaloid (-)-rhazinal [(-)-13]. ¶ Chapter four “Extending the Reaction Manifold to the Syntheses of Related Natural Products: A Formal Total Synthesis of (+)-Aspidospermidine and Syntheses of (-)-Rhazinilam and (-)-Leuconolam from (-)-Rhazinal”, describes three extensions to the reaction manifold used in the enantioselective total synthesis of alkaloid (-)-13: The acquisition in an enantioselective manner, of an intermediate previously obtained in racemic form, en route to the racemic modification of the natural product (±)-aspidospermidine [(±)-134], constitutes a formal and enantioselective total synthesis of (+)-aspidospermidine [(+)-134]. The direct deformylation of (-)-rhazinal [(-)-13], is carried out, to produce the parent alkaloid (-)-rhazinilam [(-)-1]. The pyrrole ring present in (-)-rhazinilam [(-)-1] is oxidised, to produce the related natural product (-)-Leuconolam [(-)-12] which has not, hitherto, been prepared by total synthesis. ¶Chapter five contains the experimental procedures and characterisation data associated with compounds described in chapters two to four.

Several organic transformations are mediated by group(IV) metal alkoxides. The reactivity is based on the basic nature of alkoxide group, Lewis acidic nature of the group(IV) metals, insertion of unsaturated molecules into the M-OR bond and the reduction of M(OR)4 to low valent species. The thesis deals with insertion reactions and the reductive and metathetic coupling reactions mediated by group(IV) metal alkoxides. Titanium(IV) alkoxides and zirconium(IV) alkoxides promote insertion and metathesis of aryl isocyanates. It was observed that aryl isocyanates underwent double insertion in addition to mono insertion. At room temperature, head to tail double insertion is observed whereas at elevated temperatures, head to head double insertion occurred leading to metathesis. The reaction has also been extended to metathesis between heterocumulenes and heteroalkenes. Titanium and zirconium carry out these reactions with different efficiencies. The reasons for these differences have been sought through computational methods. New organic transformations promoted by group(IV) metal alkoxides that are reduced with Grignard reagents and silanes have been explored. Grignard reagents do show reactivity towards imines in the presence of group(IV) metal alkoxides. The reactions have been studied with stoichiometric and catalytic amounts of titanium(IV) isopropoxide and are shown to follow different pathways. Isotope labeling studies indicate that alkylated products formed in stoichiometric reactions arise due to metal-olefin intermediates. However in catalytic reactions, a metal-alkyl complex is responsible for alkylation. Titanium(IV) alkoxides when used in combination with silanes such as phenylsilane bring about the reductive coupling of imines. One of the interesting features is that this pinacol type coupling is diastereospecific.

Among Nature's creation, terpenoids are more versatile and exciting natural products. In a remarkable display of synthetic ingenuity and creativity, nature has endowed terpenes with a bewildering array of carbocyclic frameworks with unusual assemblage of rings and functionalities. This phenomenal structural diversity of terpenes makes them ideal targets for developing and testing new synthetic strategies for efficient articulation of carbocyclic frameworks. The thesis entitled “Synthetic Approaches to Herbertenoid and Cuperenoid Sesquiterpenes" describes the application of ring-closing metathesis and Claisen rearrangement based approach to some herbertenoid and cuparenoid natural products. The results are described in five different sections, viz., a) First Total Synthesis of (±)-γ-Herbertenol; b) First Total Synthesis of (±)-HM-2; c) First Total Synthesis of (±)-HM-4 and HM-3; d) First Total Synthesis of Herbertenones A and B; and e) Total Synthesis of Lagopodin A. Complete details of the experimental procedures and the spectroscopic data were provided in a different section. A brief introduction is provided wherever appropriate to keep the present work in proper perspective. The compounds are sequentially numbered (bold), references are marked sequentially as superscripts and listed in the last section of the thesis. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. To begin with, the first total synthesis of γ-herbertenol, an herbertene isolated from a non-herbertus source, has been accomplished starting from 3,5-dimethylphenol. Claisen rearrangement of 3-(3-methoxy-5-methylphenyl)but-2-en-1-ol, obtained in eight steps from 3,5-dimethylphenol, furnished a γ,δ-unsaturated ester, which was transformed into 4-aryl-4,5,5-trimethylcyclopent-2-enone employing RCM reaction as the key step, which was further transformed into (±)-γ-herbertenol, which exhibited spectral data identical to that of the natural product. An alternative RCM reaction based methodology was also developed for the synthesis of γ-herbertenol methyl ether starting from ethyl 3-aryl-3-methylpent-4-enoate, an intermediate in the first sequence. The methodology has been extended for the synthesis of the putative structure of HM-2 starting from 2,4-dimethoxy-5-methylacetophenone via the corresponding ethyl 3-aryl-3-methylpent-4-enoate. However, the spectral data of the synthetic compound was found to be different from that reported for the natural product. A new cuperenoid structure for HM-2 was proposed. Total synthesis of cuparene-1,4-diol starting from toluhydroquinone, followed by its conversion to mono methyl ether and mono acetyl derivative confirmed the structures of HM-1 and the revised structure of HM-2. In a similar manner, total synthesis of the putative structure of HM-3 starting from 4-methylresorcinol dimethyl ether proved it to be wrong. A cupereniod structure, HM-4 monoacetate was proposed for HM-3. Synthesis of HM-4, and its conversion to mono acetate confirmed the structures of HM-4 and the revised structure of HM-3. The methodology has been further extended to the first total synthesis of herbertenones A and B starting from 2,5-dimethoxybenzaldehyde. By readily identifying the similarity between lagopodin A and HM-1 and HM-2, an intermediate in the synthesis of HM-1 and HM-2 has been further transformed in to (±)lagopodin A.

This thesis is divided into four separate parts with amino alcohols as the common feature. The first part of the thesis describes the development of an efficient three-component approach to the synthesis of α-hydroxy-β-amino esters. Utilizing a highly diastereoselective Rh(II)-catalyzed 1,3-dipolar cycloaddition of carbonyl ylides to various aldimines, syn-α-hydroxy-β-amino esters are formed in high yields and excellent diastereoselectivities. An asymmetric version was also developed by employing chiral α-methylbenzyl imines as dipolarophiles yielding enantiomerically pure syn-α-hydroxy-β-amino esters. This methodology was also applied on a short asymmetric synthesis of the paclitaxel side-chain as well as in an asymmetric synthetic approach towards the proteasome inhibitor omuralide. Furthermore, the use of chiral Rh(II) carboxylates furnishes the syn-α-hydroxy-β-amino esters in moderate enantioselectivity (er up to 82:18), which indicates that the reaction proceeds via a metal-associated carbonyl ylide. The second part describes the development of a 1,3-dipolar cycloaddition reaction of azomethine ylides to aldehydes for the synthesis of α-amino-β-hydroxy esters. Different methods for the generation of the ylides, including Vedejs’ oxazole methology and an Ag(I)/phosphine-catalyzed approach have been evaluated. The best results were obtained with the Ag(I)/phosphine approach, which yielded the desired α-amino-β-hydroxy ester in 68% yield and 3.4:1 syn:anti-selectivity. The last two parts deals with the total synthesis of the amino alcohol-containing natural products D-erythro-sphingosine and (−)-stemoamide. The key transformation in the sphingosine synthesis is a cross-metathesis reaction for the assembly of the polar head group and the aliphatic chain. In the stemoamide synthesis, the key feature is an iodoboration/Negishi/RCM-sequence for the construction of the β,γ-unsaturated azepine core of stemoamide followed by a stereoselective bromolactonization/1,4-reduction strategy for the installation of the requisite C8-C9 trans-stereochemistry. / QC 20100820

In this thesis, carbohydrate mimicry is investigated through the syntheses of carbohydrate analogues and evaluation of their inhibitory effects on carbohydrate-processing enzymes. Galactofuranosides are interesting structures because they are common motifs in pathogenic microorganisms but not found in mammals. M.tuberculosis, responsible for the disease tuberculosis, has a cell wall containing a repeating unit of alternating (1→5)- and (1→6)-linked β-D-galactofuranosyl residues. Synthetic inhibitors of the enzymes involved in the biosynthesis of the cell wall could find great therapeutic use. The first part of this thesis describes the first synthesis of the hydrolytically stable carbasugar analogue of galactofuranose, 4a-carba-β-D-Galf, and the synthetic work of synthesising β-linked pseudodisaccharides containing carba-Galf, which were tested for glycosyltransferease inhibitory activity. The pseudodisaccharide carba-Galf-(β1→5)-carba-Galf was found to be a moderate inhibitor of the glycosyltransferase GlfT2 of M.tuberculosis. The thesis also describes how a general method towards biologically relevant α-linked carba-Galf ethers was developed. The final part of this thesis is focussed on the formation of nitrogen-linked monosaccharides without the participation of the anomeric centre. Such a mode of coupling is called tail-to-tail neodisaccharide formation. The couplings of carbohydrate derivatives via the Mitsunobu reaction are successfully reported herein. The method describes the key introduction of an allylic alcohol in the electrophile and the subsequent functionalisation of the alkene to obtain the neodisaccharide. Two synthesised neodisaccharides presented in this thesis have been sent to be tested for glycosidase inhibitory activity. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript. Paper 5: Manuscript. Paper 6: Manuscript.

Externally initiated o-tolyl initiated poly(3-hexylthiophene) (P3HT) was synthesized according to Grignard metathesis polymerization at varying chain length to compare number average molecular weights (Mn) obtained by gel permeation chromatography (GPC) and 1H NMR end group analysis. The extent of overestimation by GPC (1.3) was determined to be lower than previously reported for low Mn polymers. However, an apparent GPC quantification limit was observed as NMR Mn correlated well to predicted results. Static light scattering studies on high Mn polymers provided evidence that the true molecular weight was more similar to GPC-derived Mn. Despite nearly 100% external initiation efficiency, at a certain Mn limit new uninitiated chains may be synthesized. It is suggested that the synthesis of externally initiated P3HT should be limited to Mn below 40 kDa to ensure fully externally initiated chains. A proposal for the synthesis of externally initiated macrocyclic P3HT will also be discussed.