Short approach toward the nonracemic A,B,E tricyclic core of calyciphylline B-type alkaloids

Abstract: A suitably functionalized tricyclic adduct containing the common A,B,E rings found in calyciphylline B-type alkaloids was obtained in nine linear steps. The key transformation features an efficient one-pot sequence of intramolecular Vilsmeier–Haack cyclization and azomethine ylide 1,3-dipolar cycloaddition in which three cycles, three new carbon–carbon bonds, and three stereocenters are formed, one being fully substituted. This work also demonstrates the first use of a chiral, nonracemic cyclic enol ether as an internal carbon nucleophile

General approach toward aspidospermatan-type alkaloids using one-pot Vilsmeier–Haack cyclization and azomethine ylide cycloaddition

Abstract: The development of a new one-pot reaction sequence afforded the tricyclic core of several aspidospermatan-type alkaloids from a linear, densely functionalized substrate. The key sequence features a highly chemoselective formamide activation that triggered a Vilsmeier–Haack cyclization, followed by an azomethine ylide generation and intramolecular cycloaddition. The choice of nucleophile, azomethine ylide precursor, and dipolarophile was crucial to the success of the sequence

Preparation of conformationally restricted β2,2- and β2,2,3-amino esters and derivatives containing an all-carbon quaternary center

Abstract: β-Amino acids are routinely incorporated into peptidic drugs to increase their stability and to incur conformational biases. However, the synthesis of highly substituted β-amino acids still represents a great challenge. A new approach to their preparation is reported involving a Vilsmeier–Haack reaction with nonaromatic carbon nucleophiles. The highly challenging preparation of contiguous tertiary and all-carbon quaternary centers was successfully used to generate several β2,2,3-amino esters, such as derivatives of homoproline, homoalanine, and homopipecolinic esters

Competition between alkenes in intramolecular ketene-alkene [2 + 2] cycloaddition: What does it take to win?

Abstract: In the course of developing a new synthetic methodology using ketenes in sequential cycloaddition steps, we were faced with a competition problem with molecules containing a ketene tethered to more than one reacting partner. To pinpoint the electronic and tethering requirements for a chemoselective reaction, we undertook a series of ketene−alkene [2 + 2] cycloaddition competition experiments. Those experiments were conducted on molecules containing either two identical alkenes having different tether lengths or two alkenes having the same tether length but being electronically different. We demonstrated that the reaction is much faster for forming five-membered rings than six-membered rings and calculated the Hammett constant ρ for intramolecular ketene−alkene [2 + 2] cycloadditions to be −1.39

Synthesis of the tricyclic core of alkaloid securinol B using a cascade of vilsmeier-haack and mannich cyclizations

Abstract: The Securinega alkaloids are a family of approximately 20 tetracyclic compounds isolated from diverse Securinega, Phyllanthus, and Margaritaria species of the Euphorbiaceae plant family. Most of these alkaloids possesses an indolizidine skeleton fused with an azabicyclo[3.2.1]octane system, as in securinine (1), the major Securinega alkaloid, and in viroallosecurinine (2) (Figure 1). These compounds exhibit interesting biological activity, such as acting on the central nervous system as γ-aminobutyric acid receptor antagonists. In 1965, Tamura and Iwamoto isolated much rarer hydroxy-substituted Securinega alkaloids, securinol A and B (0.0005% and 0.00009%, respectively), from S. suffriticosa. The structure of these alkaloids was first assigned as 3 and 4. In 1991, Arbain and Sargent identified 5 as the revised structure of securinol A, from X-ray analysis of its crystalline hydrobromide salt. Since both securinol A and B give viroallosecurinine (2) upon treatment with mesyl chloride and pyridine, it was therefore suggested that securinol B has structure 6

Sequential One-pot Vilsmeier–Haack and organocatalyzed Mannich cyclizations to functionalized benzoindolizidines and benzoquinolizidines

Abstract: The development of new one-pot sequential cyclizations involving a Vilsmeier–Haack reaction followed by an organocatalyzed Mannich reaction is reported. This synthetic strategy gives access to functionalized indolizidines and quinolizidines in one operation from readily synthesized precursors. Yields and diastereoselectivities are good to excellent when formamides are used to trigger the key step, bearing either an electron-rich aryl or a pyrrole as the nucleophilic partner in the first cyclization

Studies toward total synthesis of (±)-caldaphnidine C via one-pot sequential intramolecular Vilsmeier–Haack and azomethine ylide 1,3-dipolar cycloaddition

An application of a one-pot sequential Vilsmeier–Haack cyclization and intramolecular azomethine ylide 1,3-dipolar cycloaddition toward the total synthesis of (±)-caldaphnidine C is presented. It allowed an efficient formation of three cycles with perfect control of four of the five newly created stereogenic centers including one all-carbon quaternary center. Two synthetic strategies to produce the key-step precursor, the investigation and optimization of the cyclization partners (nucleophile, azomethine ylide, and dipolarophile), and further derivatization of the cycloadduct are reported

Mono-boratabenzene and phospholyl zirconocene(IV) derivatives : towards mixed heterocycles zirconocene complexes

In hopes of extending the existing knowledge on the chemistry of phospholyl and boratabenzene complexes of zirconium, which have shown potential notably as polymerization catalysts, this study aims at exploring the synthesis of mono boratabenzene and mono phospholyl zirconium complexes and at studying their reactivity towards the formation of mixed (boratabenzene)(phospholyl)zirconium complexes. Several derivatives of (η5-phospholyl)Zr(NMe2)xCl3−x and (η6-boratabenzene-NMe2)Zr(NMe2)xCl3−x were synthesized and used as precursors for the formation of mixed (boratabenzene)(phospholyl)zirconium complexes

Synthèse totale énantiosélective de la (11R)-(-)-8-épi-11-hydroxy-aphidicoline par réactions de Diels-Alder/aldol transannulaires en tandem

Au cours de cette thèse, nous verrons la synthèse totale de la (11R )-(-)-8-épi-11-hydroxy-aphidicoline et toutes les recherches pour y arriver. Le présent ouvrage sera divisé en quatre grandes parties. Dans un premier temps, nous étudierons la synthèse du tétracycle, en passant par un intermédiaire macrocyclique à quinze membres. Or, un problème de déprotection nous a obligé [i.e. obligés] à synthétiser plusieurs macrocycles, que nous aborderons un à un. Dans cette première partie seront aussi présentées les améliorations apportées à la séquence de première génération, soit l'augmentation de la convergence par un couplage de Stille et l'augmentation des rendements, surtout en ce qui a trait aux étapes-clé. Deuxièmement, nous nous attarderons sur les transformations du cycle D du produit tétracyclique de Diels-Alder/aldol transannulaires en tandem, en explorant toutes les voies essayées. En troisième lieu, nous nous pencherons sur les transformations du cycle A du squelette tétracyclique, en passant par les études modèles sur une décalone. Cette section se terminera par l'achèvement de la synthèse de la (11R )-(-)-8-épi-11-hydroxy-aphidicoline. Finalement, nous aborderons les voies envisagées pour compléter la synthèse du produit naturel, soit l'aphidicoline, en déviant quelque peu de la séquence développée. Une synthèse de troisième génération, plus courte et plus efficace mais toujours en utilisant les informations présentées dans cette thèse, sera aussi proposée

Synthesis of the tetracyclic core of daphnilactone B-type and yuzurimine-type alkaloid

Abstract: The core of daphnilactone B-type and yuzurimine-type alkaloids was synthesized in only 16 steps from a known β-allyl-γ-butyrolactone. The key sequence of Vilsmeier–Haack cyclization and intramolecular azomethine ylide cycloaddition allowed the construction of, in a single step, three of the five rings common to all alkaloids found in both of these classes with perfect chemocontrol