Thursday 23 November 2017

Catalytic C-H amination at its limits: challenges and solutions

Catalytic C-H amination at its limits: challenges and solutions

Org. Chem. Front., 2017, 4,2500-2521
DOI: 10.1039/C7QO00547D, Review Article

Damien Hazelard, Pierre-Antoine Nocquet, Philippe Compain
Pushing C-H amination to its limits fosters innovative synthetic solutions and offers a deeper understanding of the reaction mechanism and scope.

Catalytic C–H amination at its limits: challenges and solutions

Damien Hazelard,^a Pierre-Antoine Nocquet^a and Philippe Compain*^a

*Corresponding authors

^aLaboratoire de Synthèse Organique et Molécules Bioactives (SYBIO), Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), 25 rue Becquerel, 67087 Strasbourg Cedex 2, France
E-mail: philippe.compain@unistra.fr

Abstract

Catalytic C–H amination reactions enable direct functionalization of non-activated C(sp³)–H bonds with high levels of regio-, chemo- and stereoselectivity. As a powerful tool to unlock the potential of inert C–H bonds, C–H amination chemistry has been applied to the preparation of synthetically challenging targets since major simplification of synthetic sequences are expected from this approach. Pushing C–H amination to its limits has led to a deeper understanding of the reaction mechanism and scope. In this review, we present a description of the specific challenges facing catalytic C–H amination in the synthesis of natural products and related compounds, as well as innovative tactics created to overcome them. By identifying and discussing the major insights gained and strategies designed, we hope that this review will stimulate further progress in C–H amination chemistry and beyond.

Conclusion Since the seminal works of Du Bois in the early 2000s, the pace of discovery in the field of metal-catalysed C–H amination has been breath-taking. Not surprisingly, this synthetic tool has been applied to the total synthesis of many compounds of interest, given the high prevalence of the amino group in natural products and synthetic pharmaceuticals.67 Chemist’s confidence in the high potential of the C–H amination methodology to unlock inert C–H bonds has been demonstrated by its application to more and more challenging substrates. This has been a powerful drive for progress in the field. New valuable insights have been gained allowing, for example, a better regiochemical control via stereoelectronic and/or conformational effects. Innovative strategies have been discovered to direct the insertion event in substrates bearing a large degree of attendant functionality. Solutions have spanned from the elegant exploitation of kinetic isotope effects to the tactical use of protecting groups with different sizes or electronic characteristics. Systematic exploration of different catalytic systems has been also performed leading to the opening of new possibilities in C–H amination technology. Manganese-based catalysts have thus given rise to nitrenoids that overcome the low reactivity of primary aliphatic C–H bonds without interfering with weaker secondary/tertiary C–H bonds. Despite these impressive achievements, much remains to be done. Counterintuitive selectivity and unexplained reactivity should serve as a reminder that further studies are highly needed to understand in depth catalytic C–H amination chemistry. Many challenges remain on the way, from basic to applied research. A clear mechanistic view based on definitive evidence concerning the details of the C–N bond forming process would undoubtedly facilitate the rational design of efficient catalytic systems leading to higher regio-, chemio- and stereoselectivity. In particular, the quest for site-selective C–H amination through catalyst control has to be pursued.10d,e In this context, the development of efficient intermolecular C–H amination process still represents a major challenge and upcoming advancements are expected to increase the impact of this technology in organic synthesis. Future progress made in the field of catalytic C–H amination chemistry might also lead to industrial-scale applications in the next decade. It is likely that total synthesis of synthetically challenging targets related to natural products will continue to be a powerful driving force towards this goal.

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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

amcrasto@gmail.com

Tuesday 21 November 2017

Highly active, separable and recyclable bipyridine iridium catalysts for C–H borylation reactions

Hind Mamlouk,^a Jakkrit Suriboot,^b Praveen Kumar Manyam,^a Ahmed AlYazidi,^a David E. Bergbreiter*^b and Sherzod T. Madrahimov*^a

*Corresponding authors

^aDepartment of Chemistry, Texas A&M University at Qatar, P.O. Box 23874, Doha, Qatar
E-mail: sherzod.madrahimov@qatar.tamu.edu

^bDepartment of Chemistry, Texas A&M University, College Station, USA
E-mail: bergbreiter@tamu.edu

Abstract

Iridium complexes generated from Ir(I) precursors and PIB oligomer functionalized bpy ligands efficiently catalyzed the reactions of arenes with bis(pinacolato)diboron under mild conditions to produce a variety of arylboronate compounds. The activity of this PIB bound homogeneous catalyst is similar to that of an original non-recyclable catalyst which allows it to be used under milder conditions than other reported recyclable catalysts. This oligomer-supported Ir catalyst was successfully recovered through biphasic extraction and reused for eight cycles without a loss of activity. Biphasic separation after the initial use of the catalyst led to an insignificant amount of iridium leaching from the catalyst to the product, and no iridium leaching from the catalyst was observed in the subsequent recycling runs. Arylboronate products obtained after extraction are sufficiently pure as observed by ¹H and ¹³C-NMR spectroscopy that they do not require further purification.

Hind MAMLOUK, PhD

R&D in Organic Materials Chemistry Looking for a New Challenge

3-Chloro-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)anisole (5). Transparent oil. Yield: 87%.

1H NMR (600 MHz, CDCl3) δ 7.37 (s, 1H), 7.22 – 7.16 (m, 1H), 6.99 (s, 1H), 3.82 (s, 3H), 1.34 (s, 12H);

13C NMR (101 MHz, CDCl3) δ 159.88, 134.57, 126.84, 117.71, 117.43, 84.15, 55.52, 24.82.

GCMS: RT=14.55 min, M+ = 268.1 vs MW= 268.54 g.mol-1 .

Sherzod Madrahimov

Asst. Prof.

Texas A&M University at Qa... , Doha · Science

Research experience

Aug 2015–present

Asst. Prof.

Texas A&M University at Qatar · Chemistry

Qatar · Doha
Jul 2012–Jul 2015

PostDoc Position

Northwestern University · Department of Chemistry

United States · Evanston
Aug 2007–Jul 2012

Graduate student

University of Illinois, Urbana-Champaign · Department of Chemistry

United States · Urbana

Texas A&M University at Qatar

David Bergbreiter
Professor
Contact

Department of Chemistry
Texas A&M University
College Station, TX 77843-3255

P: 979-845-3437
F: 979-845-4719
bergbreiter@chem.tamu.edu

Current Activities

Our group explores new chemistry related to catalysis and polymer functionalization using the tools and precepts of synthetic organic chemistry to prepare functional oligomers or polymers that in turn are used to either effect catalysis in a greener, more environmentally benign way or to more efficiently functionalize polymers. Often this involves creatively combining the physiochemical properties of a polymer with the reactivity of a low molecular weight compound to form new materials with new functions. These green chemistry projects involve undamental research both in synthesis and catalysis but has practical aspects because of its relevance to practical problems.
A common theme in our catalysis studies is exploring how soluble polymers can facilitate homogeneous catalysis. Homogeneous catalysts are ubiquitously used to prepare polymers, chemical intermediates, basic chemicals and pharmaceuticals. Such catalysts often use expensive or precious metals or expensive ligands or are used at relatively high catalyst loadings. The products often contain traces of these catalysts or ligands - traces that are undesirable for esthetic reasons or because of the potential toxicity of these impurities. Both the cost of these catalysts of these issues require catalyst/product separation - separations that often are inefficient and lead to chemical waste. These processes also use volatile organic solvents - solvents that have to be recovered and separated. Projects underway in our lab explore how soluble polymers can address each of these problems. Examples of past schemes that achieve this goal in a general way as highlighted in the Figure below.
We also use functional polymers to modify existing polymers. Ongoing projects involve molecular design of additives that can more efficiently modify polymers' physical properties. We also use functional polymers in covalent layer-by-layer assembly to surface polymers' surface chemistry. An example of this work is our use of 'smart' polymers that reversibly change from being water soluble cold to being insoluble and hydrophobic on heating. Such polymers' have been used by us to prepare 'smart' catalysts, 'smart' surfaces and membranes, and to probe fundamental chemistry underlying temperature and salt-dependent protein solvation.

Jakkrit Suriboot

Research Assistant at Texas A&M University

Image result for Praveen Kumar Manyam TEXAS

Dr. Praveen Kumar

Title: Research Assistant Professor

Education: M.S., I.I.T. Roorkee
Ph.D., Panjab University Chandigarh (2008)
Visiting Fellow (w/ Prof. G. G. Balint-Kurti), Bristol University, UK
Postdoctoral Research Associate (w/ Prof. Svetlana Malinovskaya), Stevens Institute of Technology, Hoboken, NJ
Senior Postdoctoral Research Associate (w/ Prof. Seogjoo Jang), Queens College of CUNY, NY
Office: Chemistry 010
Phone: 806-742-3124
Email: praveen.kumar@ttu.edu

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“ORG SYN INT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Thursday 16 November 2017

Synthesis with Catalysts

Axay Parmar

Founder at Synthesis with Catalysts Pvt. Ltd

axayrp@gmail.com

+91- 999-997-2051

info@synthesiswithcatalysts.com

Synthesis with Catalysts Pt. Ltd. is a company started with an aim to produce chiral and achiral precious metal based catalysts on commercial scale in line with “Clean and Green India” and “Make in India” vision of Government of India. These catalysts have been developed to promote efficient, economical and environmentally benign processes for the target compounds being produced in aroma, fine chemicals and pharmaceutical industries. These catalysts and their intermediates are also extensively used in academic and industrial R&D centres across globe. In India these catalysts are currently imported at a very prohibitive cost, due to which their use is limited for want of funds. In this direction Synthesis with Catalysts Pvt. Ltd. is striving to make these products available to indigenously available at a very competitive price at small and bulk scale. We are also doing in-house research to optimize process parameters ofvarious organic transformations particularly asymmetric hydrogenation and isomerization reactionsfor customers as and when required.
For the list of our products please visit our wesitewww.synthesiswithcatalysts.com
ABOUT US

Our vision is to be the most respected catalyst manufacturing company in the country
Our goal is to help our customers:
to further improve their production methodologies

increase productivity,
develop new products with the intervention of catalysts to make the process green and clean

Highly selective catalysts for intended application
Competitive pricing with short delivery lead times
Custom product and process development

Activities:A
Manufacture of Homogeneous catalysts using metal ions viz. Rh, Pt, Ir, Pd, Ru, Co, and Mn
Manufacture of ligands and intermediates
Pharmaceutical, bulk drugs, API, aroma chemical, essential oil industries served
Focus on chiral chemistries
Gram to kilogram quantities
ASYMMETR

Some of the representative reactions are:

ASYMMETRIC/ CHEMOSELECTIVE HYDROGENATION CATALYSTS

Statements

Catalysts are chiral metal complexes derived from a precious metal ion and chiral ligands
Ru used most frequently, Rh used in some cases to enhance chemo- and enantio- selectivity
Chiral ligands can be selected from variety of simple and substituted BINAP alone or in combination with chiral/achiral diamines
Suggested catalysts:
- RuCl₂[(S)-BINAP](dmf)n
- RuCl₂[(S)- tolBINAP][(S,S)-dpen]
- (S)-XylBINAP/(S)-DAIPEN-Ru
- (S)-XylBINAP/(S,S)-DPEN-Ru
- RuCl₂[(S)-tolBINAP](pica)
- RuCl[(S,S)-TsDPEN](η⁶-p-cymene)
- Ru(OTf)(TsDPEN)(p-cymene)
- BINAP-Ru(II) dicarboxylate complexes

ENANTIOSELECTIVE EPOXIDATION / HKR / DKR

Statements:

Transition metal complexes are used for chiral and non-chiral epoxidation of internal and prochiral olefins
The epoxides are important intermediates for host of industrially important products
In cases where epoxides are required in high optical purity, racemic epoxides can be subjected to Hydrolytic kinetic resolution (HKR), Aminolytic kinetic resolution (AKR), Dynamic kinetic resolutions (DKR)
Suggested catalysts:
- Mn, Co, Cr, Al complexes of chiral SALEN ligands

ASYMMETRIC ISOMERIZATION

Double bond migration reactions

Statements:

Rh-catalyzed asymmetric isomerization of allylic amines into the corresponding enamines is one of the most revered industrial organic transformation in asymmetric catalysis
It has accommodated a wide range of substrates and is a key step in the industrial production of menthol
Other industrially important isomerization is migration of terminal double bond to produce selectively trans-internal olefins
Commercially important products like isoeugenol and trans-anetheole are produced by these transformations
Suggested catalysts:
- Ru(acac)₃
- RuHCl(CO)(PPh₃)₃
- Rh/Pd complexes

Tree of popular asymmetric organic transformations

At Chiral India event in Mumbai where our technical director Dr. Abdi Is a speaker. With Basu Agarwal

Basu Agarwal

CEO at Synthesis with Catalysts Pvt Ltd

basu.ag@gmail.com

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Sunday 5 November 2017

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Org. Chem. Front., 2018, Advance Article
DOI: 10.1039/C7QO00749C, Research Article

Qiangqiang Jiang, Xinghui Qi, Chenyang Zhang, Xuan Ji, Jin Li, Renhua Liu

Oxidant- and hydrogen acceptor-free palladium catalyzed dehydrogenative cyclization of acylhydrazones to substituted oxadiazoles

Qiangqiang Jiang,a Xinghui Qi,a Chenyang Zhang,a Xuan Ji,a Jin Li*b and Renhua Liu*a

*Corresponding authors

aSchool of Pharmacy, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China
E-mail: liurh@ecust.edu.cn

bChina Catalyst Holding Co., Ltd, Jingjiu Road 3, Chemical Park, Songmu Island, Puwan New District, Dalian 116699, China
E-mail: lijin@china-catalyst.com

Abstract

An efficient method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles has been developed through palladium(0) catalyzed dehydrogenative cyclization of N-arylidenearoylhydrazides. By using this method, a wide range of functionalized and potentially biologically relevant 1,3,4-oxadiazole-containing compounds have been accessed in moderate to high isolated yields. The dehydrogenative cyclization process is characterized by the nonuse of any sacrificing hydrogen acceptors or oxidants and hydrogen gas as the only by-product, and therefore circumvents the recurring problems of over-oxidation and the compatibility with easily oxidizable functionalities in oxidation protocols.

109.6 mg, 87 % yield; White solid,

1H NMR (400 MHz, CDCl3) δ 8.13 – 8.08 (m, 2H), 8.06 (d, J = 8.7 Hz, 2H), 7.52 (m, 3H), 7.01 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H);

13C NMR (100 MHz, CDCl3) δ 164.51, 164.10, 162.33, 131.54, 129.03, 128.67, 126.80, 124.05, 116.38, 114.50, 55.46; M.p. 145-146 oC.

2-(4-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole

1H NMR CDCL3

http://pubs.rsc.org/en/Content/ArticleLanding/2018/QO/C7QO00749C#!divAbstract

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Learn spectroscopy, Valeric acid or pentanoic acid. PROBLEM 1

HE IS EXCITED TOO

Product Name: Valeric acid
CAS:109-52-4 valeric acid pentansäure acide pentanoic ペンタン酸 109-52-4 CAS C5H10O2

Valeric acid, or pentanoic acid.

This ¹³C spectrum exhibits resonances at the following chemical shifts, and with the multiplicities indicated:

Shift (ppm)	Mult.
180.8	S
33.8	T
26.8	T
22.4	T
3.58	Q

(C₅H₁₀O₂)

A= 13.4

B=22.4

C=26.8

D=33.8

E=180.6

1H NMR BELOW

t=0.78

m=1.22

m=1.46

t=2.2

s=11.8

NMR IS EASY

EVEN MOM CAN TEACH YOU