The Henry Reaction: Recent Examples
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(Nitroaldol) Reaction
MICROREVIEW DOI: 10.1002/ejoc.201101840 Biocatalytic Approaches to the Henry (Nitroaldol) Reaction Sinéad E. Milner,[a] Thomas S. Moody,[b] and Anita R. Maguire*[c] Keywords: Enzyme catalysis / Biocatalysis / C–C coupling / Nitroaldol reaction / Nitro alcohols Enantiopure β-nitro alcohols are key chiral building blocks approaches to the Henry (nitroaldol) reaction. The first for the synthesis of bioactive pharmaceutical ingredients. method is a direct enzyme-catalysed carbon–carbon bond The preparation of these target compounds in optically pure formation resulting in either an enantio-enriched or enantio- form has been the focus of much research and there has been pure β-nitro alcohol. The second approach describes the an emergence of biocatalytic protocols in the past decade. Henry reaction without stereocontrol followed by a biocata- For the first time, these biotransformations are the focus of lytic resolution to yield the enantiopure β-nitro alcohol. this review. Herein, we describe two principal biocatalytic Introduction The construction of carbon–carbon bonds is an essential element of synthetic organic chemistry. Among the various C–C bond forming reactions, the nitroaldol or Henry reac- tion[1] is one of the classical named reactions in organic synthesis. Essentially, this reaction describes the coupling of a nucleophilic nitro alkane with an electrophilic aldehyde or ketone to produce a synthetically useful β-nitro alcohol (Scheme 1).[2–5] Moreover, the Henry reaction facilitates the joining of two molecular fragments, under mild reaction conditions with the potential formation of two new ste- reogenic centres and a new C–C bond. The resulting β-nitro alcohols can undergo a variety of useful chemical transfor- mations which lead to synthetically useful structural motifs, e.g. -
Nitro Compounds As Oxidizing Agents
Class Book _______ Accession 1-f c6-- 111 Vol. ______ MORRISON . LIBRARY OF THE Municipal University of Wichita WICHITA. KANSAS THE IVERSI~Y ·o v !CHIT. NIT O COMPOUH ]).) 0 ID! ING AGENTw . SUBMITTED TO THE G.1. IDATE FACULTY IN C DI CY FOR THE ·n~G. OF TERO TS ) ) :l)-, .l)) )) ) ! ~ ):> ) ) ) .) ) .). J ) ,, ) ) ..) )) )) .) } ::> ) ) ) ) J ) J ) J ) .) ) .) ) .) ) . ) , ) ) ) ) ..) ) ) ) ) } ) J).) ' .J ) "):) ) ) .) .) ) ::> .) J ) ) ' J .) J ) ) s JUN t J.~32 Acknov~e gment is made to Professor ·orth A. Fletcher for his direction and assistance in the con uctance of this study. (ii) (ii) T BLE ·0] 1 COMTiilllT :e G.J.:J CKU ONLE DGlJCNT • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • . ii LIT OFT BLE • • • • • • • • • • • • • • • • • • • • • • • • , • • • , , • • • i V LI T OF FIGUl ~ ••••••••••••••••••••••• ' •••••••••• V IN Tl ODUCTI ON ••••••••••••••••••• , •••••••••••••••• l ~ pv. 11JI:E:t.i T L •· • • • • • • • • • • , • , •· • , , • • , • • • • • • • • • • • • • • • t ]? T B DFEECT OF TE1ft.PER TUHE •••• • • • • • • • • • • • .Id • C ffi.,' • y •••• •••••••••••• ............ •' • • • • • •••••• 13 LI 11: J:RE: CI TE'D. • • • • ••• , • • • • • • • • • • • • • • • , • • • • • •• 14 (iii) LI T O · BLE Table page I• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • .-:. • • • • • • 5 I I •• .. ................ ··~. ·~ ·· .....•..•........••.• 7 III. • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 8 rv~.. J ••••••••••••••••••••••••••••••• .•••••••••••• -
Nitroso and Nitro Compounds 11/22/2014 Part 1
Hai Dao Baran Group Meeting Nitroso and Nitro Compounds 11/22/2014 Part 1. Introduction Nitro Compounds O D(Kcal/mol) d (Å) NO NO+ Ph NO Ph N cellular signaling 2 N O N O OH CH3−NO 40 1.48 molecule in mammals a nitro compound a nitronic acid nitric oxide b.p = 100 oC (8 mm) o CH3−NO2 57 1.47 nitrosonium m.p = 84 C ion (pKa = 2−6) CH3−NH2 79 1.47 IR: υ(N=O): 1621-1539 cm-1 CH3−I 56 Nitro group is an EWG (both −I and −M) Reaction Modes Nitro group is a "sink" of electron Nitroso vs. olefin: e Diels-Alder reaction: as dienophiles Nu O NO − NO Ene reaction 3 2 2 NO + N R h 2 O e Cope rearrangement υ O O Nu R2 N N N R1 N Nitroso vs. carbonyl R1 O O O O O N O O hυ Nucleophilic addition [O] N R2 R O O R3 Other reaction modes nitrite Radical addition high temp low temp nitrolium EWG [H] ion brown color less ion Redox reaction Photochemical reaction Nitroso Compounds (C-Nitroso Compounds) R2 R1 O R3 R1 Synthesis of C-Nitroso Compounds 2 O R1 R 2 N R3 3 R 3 N R N R N 3 + R2 2 R N O With NO sources: NaNO2/HCl, NOBF4, NOCl, NOSbF6, RONO... 1 R O R R1 O Substitution trans-dimer monomer: blue color cis-dimer colorless colorless R R NOBF OH 4 - R = OH, OMe, Me, NR2, NHR N R2 R3 = H or NaNO /HCl - para-selectivity ΔG = 10 Kcal mol-1 Me 2 Me R1 NO oxime R rate determining step Blue color: n π∗ absorption band 630-790 nm IR: υ(N=O): 1621-1539 cm-1, dimer υ(N−O): 1300 (cis), 1200 (trans) cm-1 + 1 Me H NMR (α-C-H) δ = 4 ppm: nitroso is an EWG ON H 3 Kochi et al. -
Green Chemistry – Aspects for the Knoevenagel Reaction
2 Green Chemistry – Aspects for the Knoevenagel Reaction Ricardo Menegatti Universidade Federal de Goiás Brazil 1. Introduction Knoevenagel condensation is a classic C-C bond formation reaction in organic chemistry (Laue & Plagens, 2005). These condensations occur between aldehydes or ketones and active methylene compounds with ammonia or another amine as a catalyst in organic solvents (Knoevenagel, 1894). The Knoevenagel reaction is considered to be a modification of the aldol reaction; the main difference between these approaches is the higher acidity of the active methylene hydrogen when compared to an -carbonyl hydrogen (Smith & March, 2001). Figure 1 illustrates the condensation of a ketone (1) with a malonate compound (2) to form the Knoevenagel condensation product (3), which is then used to form the ,-unsaturated carboxylic compounds (3) and (4) (Laue & Plagens, 2005). R R R O O O O H O O O + base hydrolysis H O O O O R R (1) (2) (3) (4) Fig. 1. An example of the Knoevenagel reaction. Subsequent to the first description of the Knoevenagel reaction, changes were introduced using pyridine as the solvent and piperidine as the catalyst, which was named the Doebner Modification (Doebner, 1900). The Henry reaction is another variation of the Knoevenagel condensation that utilises compounds with an -nitro active methylene (Henry, 1895). The general mechanism for the Knoevenagel reaction, which involves deprotonation of the malonate derivative (6) by piperidine (5) and attack by the formed carbanion (8) on the carbonyl subunit (9) as an aldol reaction that forms the product (10) of the addition step is illustrated in Fig. -
Electrochemistry and Photoredox Catalysis: a Comparative Evaluation in Organic Synthesis
molecules Review Electrochemistry and Photoredox Catalysis: A Comparative Evaluation in Organic Synthesis Rik H. Verschueren and Wim M. De Borggraeve * Department of Chemistry, Molecular Design and Synthesis, KU Leuven, Celestijnenlaan 200F, box 2404, 3001 Leuven, Belgium; [email protected] * Correspondence: [email protected]; Tel.: +32-16-32-7693 Received: 30 March 2019; Accepted: 23 May 2019; Published: 5 June 2019 Abstract: This review provides an overview of synthetic transformations that have been performed by both electro- and photoredox catalysis. Both toolboxes are evaluated and compared in their ability to enable said transformations. Analogies and distinctions are formulated to obtain a better understanding in both research areas. This knowledge can be used to conceptualize new methodological strategies for either of both approaches starting from the other. It was attempted to extract key components that can be used as guidelines to refine, complement and innovate these two disciplines of organic synthesis. Keywords: electrosynthesis; electrocatalysis; photocatalysis; photochemistry; electron transfer; redox catalysis; radical chemistry; organic synthesis; green chemistry 1. Introduction Both electrochemistry as well as photoredox catalysis have gone through a recent renaissance, bringing forth a whole range of both improved and new transformations previously thought impossible. In their growth, inspiration was found in older established radical chemistry, as well as from cross-pollination between the two toolboxes. In scientific discussion, photoredox catalysis and electrochemistry are often mentioned alongside each other. Nonetheless, no review has attempted a comparative evaluation of both fields in organic synthesis. Both research areas use electrons as reagents to generate open-shell radical intermediates. Because of the similar modes of action, many transformations have been translated from electrochemical to photoredox methodology and vice versa. -
Nitroalkanes As Central Reagents in the Synthesis of Spiroketals
Molecules 2008, 13, 319-330 molecules ISSN 1420-3049 © 2008 by MDPI www.mdpi.org/molecules Review Nitroalkanes as Central Reagents in the Synthesis of Spiroketals Roberto Ballini 1,*, Marino Petrini 1 and Goffredo Rosini 2 1 Dipartimento di Scienze Chimiche, Università di Camerino, via S.Agostino, 1, I-62032 Camerino, Italy; E-mail: [email protected]. 2 Dipartimento di Chimica Organica ‘A. Mangini’, Alma Mater Studiorum–Università di Bologna, Viale del Risorgimento n. 4, 40136 Bologna, Italy; E-mail: [email protected]. * Author to whom correspondence should be addressed; E-mail: [email protected]; Fax: +39 0737 402297 Received: 8 January 2008; in revised form: 2 February 2008 / Accepted: 4 February 2008 / Published: 7 February 2008 Abstract: Nitroalkanes can be profitably employed as carbanionic precursors for the assembly of dihydroxy ketone frameworks, suitable for the preparation of spiroketals. The carbon-carbon bond formation is carried out exploiting nitroaldol and Michael reactions, while the nitro to carbonyl conversion (Nef reaction) ensures the correct introduction of the keto group. Several spiroketal systems endowed with considerable biological activity can be prepared using this synthetic strategy. Keywords: Conjugate addition, Nef reaction, nitroaldol reaction, nitroalkanes, spiroketals. 1. Introduction The spiroketal moiety is a key motif embodied in a large number of natural products present in plants, fungi, insect secretions, shellfish toxins and other living organisms [1-5]. Many of these compounds also display a considerable biological activity as antibiotics and pheromones. From a synthetic standpoint, among various practical strategies currently available for the assembling of the spiroketal unit, the one based on the acid promoted intramolecular acetalization of dihydroxy ketone derivatives 1 firmly occupies a prominent position (Scheme 1). -
Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes: Recent Results
Chem. Rev. 2005, 105, 933−971 933 Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes: Recent Results Roberto Ballini,* Giovanna Bosica, Dennis Fiorini, Alessandro Palmieri, and Marino Petrini* Dipartimento di Scienze Chimiche, Universita` di Camerino, via S. Agostino, 1, I-62032 Camerino, Italy Received September 30, 2004 Contents Conjugate additions using highly stabilized carban- ions are still of interest since a growing number of 1. Introduction 933 these procedures can be carried out in environmen- 2. General Aspects of the Conjugate Addition of 934 tally benign solvents such as water and using cata- Nitroalkanes lytic amounts of the basic promoter. In addition, the 2.1. Multiple Additions 934 achievement of diastereo- and enantioselective pro- 2.2. Basic Catalysts 935 cesses is no longer an exclusive domain of highly 3. New Basic Catalysts for the Conjugate Addition 936 reactive carbanionic systems working in carefully 4. Diastereoselective Conjugate Additions 936 controlled conditions3 but can be nowadays conducted 4.1. Intermolecular Additions 936 even at room temperature using easily available 4.2. Intramolecular Additions 948 substrates and suitable base/solvent combinations. 5. Asymmetric Conjugate Additions Promoted by 949 Nitroalkanes are a valuable source of stabilized Chiral Catalysis carbanions since the high electron-withdrawing power 6. Conjugate Addition−Elimination Reactions 953 of the nitro group provides an outstanding enhance- R 7. Synthetic Applications 957 ment of the hydrogen acidity at the -position (cf. pka ) 4-8 7.1. Pyrrolidines and Derivatives 957 MeNO2 10). Nitronate anions 2 that can be generated from nitroalkanes 1 using a wide range of 7.2. Lactones and Oxygenated Heterocycles 960 bases act as carbon nucleophiles with common elec- 7.3. -
UNITED STATES PATENT Orricsg. 2,623,904 Nrrao ALDEHYDES and Preraaarion TPEREGF Curtis W
Patented Dec. 30, ‘1952 2,623.04 UNITED STATES PATENT orricsg. 2,623,904 nrrao ALDEHYDES AND PRErAaArioN _ TPEREGF Curtis W. Smith, ‘Berke ley, Calif., assignor to Shell Development Company, San Francisco, Calif., a corporation of Delaware No Drawing. Application December 3, 1948, Serial No. 63,455 13 Claims. (Cl. 260-601) substituent group is directly linked to an- all This invention relates to organic compounds phatic carbon atom to which there is also direct and to a process for the preparation of organic ly attached an atom of hydrogen, nitro-aldehydes compounds. rather than nitro-alcohols, are produced. ' More particularly, the invention relates to The alpha-methylidene aldehydes are those nitrmaldehydes and to a process for the prepara aldehydes which have directly linked to the car tion of nitro-aldehydes. The invention also re bon atom in the alpha position relative to the lates to a new and unexpected reaction of ‘un formyl group a methylidene radical (CI-I2=),. saturated aldehydes with organic nitro com Thus, they are the alpha, beta-ole?nic aldehydes pounds whereby the nitro-aldehydes of the in in which the remaining valences of thecarbon vention may be prepared. atom in the beta position are satis?ed byatoms It has been discovered that nitro-aldehydes of hydrogen. The alpha-methylidene aldehydes may be prepared by condensing alpha-methyli may also be described by means of the formula dene aldehydes with nitro-substituted compounds wherein a nitro substituent group is directly linked to an aliphatic carbon atom to which there is also directly attached an atom of hydrogen. -
The Development and Use of Chiral 4-Dimethylaminopyridine-N-Oxide As an Organocatalyst
THE DEVOLOPMENT AND USE OF CHIRAL 4- DIMETHYLAMINOPYRIDINE-N-OXIDE AS AN ORGANOCATALYST A Dissertation Submitted to the Graduate Faculty of the North Dakota State University of Agriculture and Applied Science By Jesse Jo Joyce In Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Major Department: Chemistry and Biochemistry July 2018 Fargo, North Dakota North Dakota State University Graduate School Title The Development and Use of Chiral 4-Dimethylaminopyridine-N-Oxide as an Organocatalyst By Jesse Jo Joyce The Supervisory Committee certifies that this disquisition complies with North Dakota State University’s regulations and meets the accepted standards for the degree of MASTER OF SCIENCE SUPERVISORY COMMITTEE: Mukund Sibi, PhD Chair Gregory Cook, PhD Seth Rasmussen, PhD Yongki Choi, PhD Approved: 11/09/18 Gregory Cook, PhD Date Department Chair ABSTRACT Organocatalysis is a field that has bloomed over the last decades. With the field’s promise of being able to mimic nature and afford products in a synergistic manner to traditional Lewis acid catalysis, several interesting discoveries have been made. Owing to the vastness of the field as it exists today, this document will focus on two main aspects; cinchona alkaloid (and derivatives) as used in common carbon-carbon bond forming reactions and kinetic resolution via 4-dimethyl aminopyridine-N-oxide derivative driven acylation. Kinetic resolution via organocatalysis has the potential to react one enantiomer of a racemic mixture without affecting the other. The highlight of this screening was an s factor of 9 which was produced using optimized conditions using a catalyst designated DMAPO-IV. -
12.2% 122,000 135M Top 1% 154 4,800
We are IntechOpen, the world’s leading publisher of Open Access books Built by scientists, for scientists 4,800 122,000 135M Open access books available International authors and editors Downloads Our authors are among the 154 TOP 1% 12.2% Countries delivered to most cited scientists Contributors from top 500 universities Selection of our books indexed in the Book Citation Index in Web of Science™ Core Collection (BKCI) Interested in publishing with us? Contact [email protected] Numbers displayed above are based on latest data collected. For more information visit www.intechopen.com Chapter Hydrolase-Catalyzed Promiscuous Reactions and Applications in Organic Synthesis Yun Wang and Na Wang Abstract The potential of biocatalysis becomes increasingly recognized as an efficient and green tool for modern organic synthesis. Biocatalytic promiscuity, a new frontier extended the use of enzymes in organic synthesis, has attracted much attention and expanded rapidly in the past decade. It focuses on the enzyme catalytic activities with unnatural substrates and alternative chemical transformations. Exploiting enzyme catalytic unconventional reactions might lead to improvements in existing catalysts and provide novel synthesis pathways that are currently not available. Among these enzymes, hydrolase (such as lipase, protease, acylase) undoubtedly has received special attention since they display remarkable activities for some unexpected reactions such as aldol reaction and other novel carbon-carbon and carbon-heteroatom bond-forming reactions. This chapter introduces the recent progress in hydrolase catalytic unconventional reactions and application in organic synthesis. Some important examples of hydrolase catalytic unconventional reac- tions in addition reactions are reviewed, highlighting the catalytic promiscuity of hydrolases focuses on aldol reaction, Michael addition, and multicomponent reactions. -
First and Efficient Method for Reduction of Aliphatic and Aromatic Nitro Compounds with Zinc Borohydride As Pyridine Zinc Tetrah
Journal of the Chinese Chemical Society, 2003, 50, 267-271 267 First and Efficient Method for Reduction of Aliphatic and Aromatic Nitro Compounds with Zinc Borohydride as Pyridine Zinc Tetrahydroborato Complex: A New Stable Ligand-Metal Borohydride Behzad Zeynizadeh* and Karam Zahmatkesh Chemistry Department, Faculty of Sciences, Urmia University, Urmia 57159, Iran Pyridine zinc tetrahydroborate, [(Py)Zn(BH4)2], as a new stable ligand-metal borohydride, is prepared quantitatively by complexation of 1:1 zinc borohydride and pyridine at room temperature. This reagent effi- ciently reduces different aromatic and aliphatic nitro compounds to their primary amines in refluxing THF. In addition, the reduction shows chemoselectivity for aliphatic nitro compounds over the aromatic nitro com- pounds. Keywords: Reduction; Zinc borohydride; Nitro compound; Chemoselectivity; Amine. INTRODUCTION been reviewed. These successes prompted us to prepare 13 [(Py)Zn(BH4)2] and investigate its reducing ability. In our For over forty years, sodium borohydride has been study, we also observed that this reagent efficiently reduces widely recognized as the reagent of choice for the reduction aliphatic and aromatic nitro compounds to their correspond- of carbonyl compounds and acid chlorides in protic solvents.1 ing primary amines in refluxing THF (Scheme I). Over the past decades, the utility of sodium borohydride has been greatly expanded and different techniques and modifi- Scheme I cations have been developed for it to reduce organofunctional groups in various -
Organic Chemistry Masterclasses
Organic Chemistry Masterclasses By S. Ranganathan All rights reserved. No parts of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopy- ing, recording, or otherwise, without prior permission of the publisher. © Indian Academy of Sciences Published by Indian Academy of Sciences 2 Foreword The Masterclass series of eBooks published by the Indian Academy of Sciences, Bengaluru brings together pedagogical articles on single broad topics reproduced from Resonance, Journal of Science Education that is published monthly by the Academy since January 1996. Primarily directed at students and teachers at the undergraduate level, the journal has brought out a wide spectrum of articles in a range of scientific disciplines. Articles in the journal are written in a style that makes them appealing to readers from diverse backgrounds, and in addition, they provide a useful source of instruction that is not always available in textbooks. It is fitting that the first book in this series,Organic Chemistry Masterclasses, is by a legendary teacher, Professor Subramania Ranganathan, highly acclaimed and distinguished Organic Chemist. Ranga, as he is fondly known to generations of students at the IIT Kanpur where he taught for over three decades, has been a regular contributor to Resonance and his articles enjoy wide popularity among the journal’s readership. Indeed his first contribution toResonance was in the very first issue of the journal. We are also delighted that this collection of over fifteen articles, reformatted as an eBook will mark his 80th birthday. Those of us who were fortunate to have learned some of these topics as he was devising ways of teaching them will be very pleased that some of Ranga’s masterly instructions can reach a much wider audience through this means.