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

 

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.
STR1 STR2
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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

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Tuesday 21 November 2017

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

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

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

 

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

Hind MAMLOUK, PhD

R&D in Organic Materials Chemistry Looking for a New Challenge
Texas A&M University
 
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 .
 
 STR1 STR2
 
 
Image result for Sherzod T. Madrahimov Texas A&M University at Qatar

Sherzod Madrahimov

Asst. Prof.

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
Image result for Texas A&M University at Qatar
Texas A&M University at Qatar

A headshot
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

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





“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
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Thursday 16 November 2017

Synthesis with Catalysts

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Axay Parmar

Axay Parmar

Founder at Synthesis with Catalysts Pvt. Ltd

 

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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
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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

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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

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Double bond migration reactions
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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

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

Basu Agarwal

CEO at Synthesis with Catalysts Pvt Ltd
Phone 9999972051 (Mobile)
Email
IM basu.ag@gmail.com (Google Talk)
Chiral India 2017, Nov7-8 Ramada plaza palm grove, Juhu, Mumbai, India
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Sunday 5 November 2017

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
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 without oxidants and hydrogen acceptors.

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



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






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Learn spectroscopy, Valeric acid or pentanoic acid. PROBLEM 1


Image result for MOTHER TO TEACH NMR
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
Image result for MOTHER TO TEACH NMR






2D [1H,1H]-TOCSY, 7.4 spectrum for Valeric acid

2D [1H,1H]-TOCSY

Concentration: 100 mM
temperature: 298 K
pH: 7.4



1D DEPT90, 7.4 spectrum for Valeric acid

1D DEPT90

Concentration: 100 mM
temperature: 298 K
pH: 7.4







1D DEPT135, 7.4 spectrum for Valeric acid


1D DEPT135

Concentration: 100 mM
temperature: 298 K
pH: 7.4


2D [1H,13C]-HSQC, 7.4 spectrum for Valeric acid

2D [1H,13C]-HSQC

Concentration: 100 mM
temperature: 298 K
pH: 7.4



2D [1H,13C]-HMBC, 7.4 spectrum for Valeric acid

2D [1H,13C]-HMBC

Concentration: 100 mM
temperature: 298 K
pH: 7.4
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“ORG SYNTHESIS 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