Catalyst- and additive-free Baeyer–Villiger-type oxidation of α-iodocyclopentenones to α-pyrones: using air as the oxidant

green chemistry, spectroscopy, SYNTHESIS, Uncategorized Comments Off

Oct 152019

Graphical abstract: Catalyst- and additive-free Baeyer–Villiger-type oxidation of α-iodocyclopentenones to α-pyrones: using air as the oxidant

An efficient synthetic approach for the synthesis of α-pyrones via Baeyer–Villiger-type oxidation of α-iodocyclopentenones through a catalyst- and additive-free system using air as an environmentally benign oxidant is described. The reaction exhibits excellent functional group compatibility and provides a simple and efficient protocol for the construction of highly functionalized α-pyrones under mild reaction conditions.

Catalyst- and additive-free Baeyer–Villiger-type oxidation of α-iodocyclopentenones to α-pyrones: using air as the oxidant†

Yuanyuan Zhou,^a Xianxiao Chen,^a Xiangxiang Ling^a and Weidong Rao

*^a

Author affiliations

*Corresponding authors

^aJiangsu Key Laboratory of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China
E-mail:weidong@njfu.edu.cn

6-Cyclohexyl-4-phenyl-2H-pyran-2-one (2e)[S3]

Product 2e was obtained as a pale-yellow solid in 68% yield (52 mg) following the general procedure, mp 96-97 °C;

1H NMR (600 MHz, CDCl3) δ 7.58-7.56 (m, 2H), 7.48-7.46 (m, 3H), 6.34 (d, J = 1.3 Hz, 1H), 6.26 (d, J = 0.8 Hz, 1H), 2.48 (tt, J = 11.8, 3.3 Hz, 1H), 2.04-2.01 (m, 2H), 1.87-1.84 (m, 2H), 1.47 (qd, J = 12.5, 3.0 Hz, 2H), 1.39-1.32 (m, 2H), 1.28-1.23 (m, 2H);

13C NMR (150 MHz, CDCl3) δ 169.8, 163.6, 155.6, 136.2, 130.5, 129.1, 126.7, 108.4, 100.9, 42.5, 30.6, 25.9, 25.8

http://www.rsc.org/suppdata/c9/gc/c9gc02725d/c9gc02725d1.pdf

/////////https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C9GC02725D?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Towards cleaner PolarClean: efficient synthesis and extended applications of the polar aprotic solvent methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate

green chemistry Comments Off

Jul 302019

Graphical abstract: Towards cleaner PolarClean: efficient synthesis and extended applications of the polar aprotic solvent methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate

Abstract

As a result of recent efforts in green solvent selection, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, sold under the brand name Rhodiasolv PolarClean, has received considerable scientific and industrial attention as a possible non-toxic replacement for common polar aprotic solvents. However, the multicomponent nature and multi-step synthesis of this solvent remains an obstacle for its more widespread use and niche applications. In this work, a retrosynthetic approach was taken to identify novel shorter synthetic routes in alignment with green chemistry principles. High purity methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate was obtained in novel single-step reactions via two different base-catalysed Michael additions from readily available building blocks. The more advanced synthetic route shows great potential owing to the swift (30 min), solvent-free reaction and catalytic amounts of base (<6.5 mol%). Green metrics analysis, including Atom Economy, Complete E factor, Carbon Intensity and hazard analysis found the new synthesis to be more sustainable than the patented routes. Application of this green solvent was demonstrated for the first time for O– and N-arylation in S_NAr reaction with solvent recovery with similar or superior yields compared to other green solvents. Moreover, broad opportunities for this green solvent in membrane science were identified, where the use of conventional, toxic polar aprotic solvents in large quantities is unavoidable. Important practical solvent properties and parameters such as dielectric constant, solubility parameters, solvent miscibility and NMR residual shifts have been determined to facilitate the uptake of methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate as a green solvent.

Towards cleaner PolarClean: efficient synthesis and extended applications of the polar aprotic solvent methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate

Levente Cseri*^a and Gyorgy Szekely*^a^b

Author affiliations

*Corresponding authors

^aSchool of Chemical Engineering and Analytical Science, University of Manchester, The Mill, Sackville Street, Manchester, UK
E-mail: levente.cseri@manchester.ac.uk, gyorgy.szekely@manchester.ac.uk
Tel: +44 (0)1613062662

^bAdvanced Membranes & Porous Materials Center, Physical Science Engineering Division (PSE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
E-mail: gyorgy.szekely@kaust.edu.sa
Tel: +966128082769

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https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C9GC01958H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Triple copper catalysis for the synthesis of vinyl triazoles

green chemistry, organic chemistry Comments Off

Jul 012019

Triple copper catalysis for the synthesis of vinyl triazoles

Green Chem., 2019, Advance Article
DOI: 10.1039/C9GC01066A, Communication

Lucas L. Baldassari, Eduardo A. Cechinatto, Angélica V. Moro
Herein, we report our studies on the synthesis of vinyl 1,2,3-triazoles through a one-pot sequence, enabled by the same copper catalyst, of three different reactions: hydroboration involving an alkyne, azidation for a vinyl boronate and azide–alkyne cycloaddition.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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Triple copper catalysis for the synthesis of vinyl triazoles

Lucas L. Baldassari,^a Eduardo A. Cechinatto^a and Angélica V. Moro*^a

Author affiliations

*Corresponding authors

^aInstitute of Chemistry, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre, Brazil
E-mail:angelica.venturini@ufrgs.br
Fax: +5551 3308 6259
Tel: +55 51 3308 9637

Abstract

Herein, we report our studies on the synthesis of vinyl 1,2,3-triazoles through a one-pot sequence, enabled by the same copper catalyst, of three different reactions: hydroboration involving an alkyne, azidation for a vinyl boronate and azide–alkyne cycloaddition.

https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C9GC01066A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

///////copper catalysis, vinyl triazoles

A solvent-free catalytic protocol for the Achmatowicz rearrangement

green chemistry, spectroscopy, SYNTHESIS Comments Off

Jan 292019

Graphical abstract: A solvent-free catalytic protocol for the Achmatowicz rearrangement

Abstract

Reported here is the development of an environmentally friendly catalytic (KBr/oxone) and solvent-free protocol for the Achmatowicz rearrangement (AchR). Different from all previous methods is that the use of chromatographic alumina (Al₂O₃) allows AchR to proceed smoothly in the absence of any organic solvent and therefore considerably facilitates the subsequent workup and purification with minimal environmental impacts. Importantly, this protocol allows for scaling up (from milligram to gram), recycling of the Al₂O₃, and integrating with other reactions in a one-pot sequential manner.

A solvent-free catalytic protocol for the

Achmatowicz rearrangement

Guodong Zhao^a and Rongbiao Tong*^a^b

Author affiliations

*Corresponding authors

^aDepartment of Chemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, China
E-mail: rtong@ust.hk
Fax: +(852)23581594
Tel: +(852) 23587357

^bHKUST Shenzhen Research Institute, Shenzhen 518057, China

https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C8GC03030H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

1n: colorless oil, 0.33 g, 73% yield for 2 steps.

1H-NMR (400 MHz, DMSO) δ: 7.59–7.58 (m, 1H), 7.45 (s, 2H), 6.40 (dd, J = 3.2, 1.8 Hz, 1H), 6.29 (d, J = 3.2 Hz, 1H), 5.49 (s, 1H), 4.74–4.60 (m, 1H), 4.18–4.07 (m, 2H), 2.09–2.04 (m, 2H).

13C-NMR (100 MHz, DMSO) δ: 157.6, 142.4, 110.7, 106.1, 66.5, 62.8, 35.2. IR (KBr) 3282.9, 2928.7, 1627.4, 1562.5, 1353.8, 1174.6, 1074.0, 999.7, 918.4, 742.8 cm-1 ;

HRMS (CI+ ) (m/z) calcd. for C7H11NO5S [M]+ 221.0352; found 221.0354.

2n (EtOAc/hexane = 3:1):colorless oil (dr 7:3), 46 mg, 97%.

1H-NMR (400 MHz, DMSO) δ: 7.48–7.47 (m, 2H), 7.34–7.02 (m, 2H), 6.12–6.03 (m, 1H), 5.61–5.48 (m, 1H), 4.60 (dd, J = 8.3, 4.1 Hz, 0.7H), 4.28 (ddd, J = 8.8, 4.0, 1.3 Hz, 0.3H), 4.20–4.11 (m, 2H), 2.27–2.20 (m, 1H), 1.97–1.86 (m, 1H).

13C-NMR (100 MHz, DMSO) δ: 196.7, 196.5, 151.9, 148.3, 127.7, 126.0, 90.9, 87.2, 74.6, 70.1, 65.8, 65.8, 30.3, 29.6. IR (KBr) 3370.4, 2987.0, 1689.5, 1364.3, 1268.0, 1178.4, 1023.3, 928.3, 755.1 cm-1 ;

HRMS (CI+ ) (m/z) calcd. for C7H11NO6S [M]+ 237.0302; found 237.0315.

////////////////Achmatowicz rearrangement

A call to (green) arms: a rallying cry for green chemistry and engineering for CO2 capture, utilisation and storage

green chemistry Comments Off

Sep 172018

Graphical abstract: A call to (green) arms: a rallying cry for green chemistry and engineering for CO2 capture, utilisation and storage

A call to (green) arms: a rallying cry for green chemistry and engineering for CO₂ capture, utilisation and storage

Julien Leclaire*^a and David J. Heldebrant*^b

Author affiliations

*Corresponding authors

^aUniversité Claude Bernard Lyon 1 – CNRS, France
E-mail: julien.leclaire@univ-lyon1.fr

^bPacific Northwest National Lab, USA
E-mail: david.heldebrant@pnnl.gov

Abstract

Chemists, engineers, scientists, lend us your ears… Carbon capture, utilisation, and storage (CCUS) is among the largest challenges on the horizon and we need your help. In this perspective, we focus on identifying the critical research needs to make CCUS a reality, with an emphasis on how the principles of green chemistry (GC) and green engineering can be used to help address this challenge. We identify areas where GC principles can readily improve the energy or atom efficiency of processes or reduce the environmental impact. Conversely, we also identify dilemmas where the research needs may be at odds with GC principles, and present potential paths forward to minimise the environmental impacts of chemicals and processes needed for CCUS. We also walk a different path from conventional perspectives in that we postulate and introduce potential innovative research directions and concepts (some not yet experimentally validated) in order to foster innovation, or at least stoke conversation and question why certain approaches have not yet been attempted. With elements of historical context, technological innovation, critical thinking, and some humour, we issue a call to arms and hope you may join us in this fight.

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C8GC01962B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Julien Leclaire

David Heldebrant

Pacific Northwest National Laboratory
PO Box 999
Richland, WA 99352

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Asymmetric Organocatalysis in Drug Development—Highlights of Recent Patent Literature

green chemistry, SYNTHESIS Comments Off

May 242018

Enantioselective organocatalytic reactions published in the recent patent literature are highlighted in this review and include inter- and intramolecular phase-transfer conjugate additions catalyzed by quaternized cinchona alkaloids, a Diels–Alder reaction catalyzed by oxazaborolidine complexes, asymmetric Betti reactions, the Lonza synthesis of l-carnitine, and several Corey–Bakshi–Shibata reductions.

Asymmetric Organocatalysis in Drug Development—Highlights of Recent Patent Literature

David L. Hughes*

Cidara Therapeutics, Inc., 6310 Nancy Ridge Drive, Suite 101, San Diego, California 92121, United States

Org. Process Res. Dev., 2018, 22 (5), pp 574–584

DOI: 10.1021/acs.oprd.8b00096

Publication Date (Web): April 19, 2018

*E-mail: dhughes@cidara.com.

https://pubs.acs.org/doi/10.1021/acs.oprd.8b00096

///////////////Asymmetric Organocatalysis

Pressurized CO2 as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

green chemistry Comments Off

Apr 242018

Green Chem., 2018, 20,1754-1759
DOI: 10.1039/C8GC00008E, Communication

Open Access

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Katharina Plasch, Gerhard Hofer, Walter Keller, Sam Hay, Derren J. Heyes, Alexander Dennig, Silvia M. Glueck, Kurt Faber
Utilization of gaseous carbon dioxide as a C₁-building block in the biocatalytic ortho-carboxylation of a phenol.
The content of this RSS Feed (c) The Royal Society of Chemistry

http://pubs.rsc.org/en/content/articlehtml/2018/gc/c8gc00008e

Pressurized CO2 as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

Pressurized CO₂ as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

Katharina Plasch,^a Gerhard Hofer,^b Walter Keller,^b Sam Hay,^c Derren J. Heyes,^c Alexander Dennig,^d Silvia M. Glueck*^a^e and Kurt Faber*^a

Author affiliations

* Corresponding authors

^a Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria
E-mail:Si.Glueck@Uni-Graz.at, Kurt.Faber@Uni-Graz.at

^b Institute of Molecular Biosciences, University of Graz, Humboldstrasse 50, 8010 Graz, Austria

^c Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK

^d Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, Petersgasse 12, 8010 Graz, Austria

^e Austrian Centre of Industrial Biotechnology (ACIB), Petersgasse 14, 8010 Graz, Austria

Abstract

The utilization of gaseous carbon dioxide instead of bicarbonate would greatly facilitate process development for enzyme catalyzed carboxylations on a large scale. As a proof-of-concept, 1,3-dihydroxybenzene (resorcinol) was carboxylated in the ortho-position using pressurized CO₂ (∼30–40 bar) catalyzed by ortho-benzoic acid decarboxylases with up to 68% conversion. Optimization studies revealed tight pH-control and enzyme stability as the most important determinants.


Fig. 1 (a) Enzyme-catalyzed de/carboxylation of resorcinol (1). Carboxylated product 2 is a mixture of regio-isomeric 2,6- (2,6-dhba, 2a) and 2,4-dihydroxybenzoic acid (2,4-dhba, 2b) with a ratio of 3:4;^10b (b) CO₂ pressure dependence of the carboxylation of 1 using 2,3-DHBD_Ao; (c) carboxylation activity of decarboxylases with CO₂ (30 bar) using 1 as a substrate; (d) stopped-flow measurements of the decarboxylation of 2,6-dhba (2a) with pressure-pretreated (≤1.5 kbar) 2,3-DHBD_Ao and 2,6-DHBD_Rs.

Conclusion

In summary, we have demonstrated that pressurized carbon dioxide can be used directly as a carboxylating agent in the enzyme catalyzed o-carboxylation of a phenol as an alternative to the high concentration of bicarbonate. Two enzyme candidates (2,3-DHBD_Ao and SAD_Tm) readily accepted the alternative CO₂ source for the carboxylation of the model substrate resorcinol. In contrast, 2,6-DHBD_Rs was inapplicable under CO₂ pressure due to irreversible inactivation, which was correlated to a decrease in pH caused by the dissociation of H₂CO₃.

Overall, the use of pressurized CO₂ gas significantly improves the efficiency of biocatalytic carboxylations and facilitates downstream-processing of this benign and sustainable approach in using CO₂ as a carbon feedstock for the synthesis of organic acids.

Katharina Plasch

DOCTORAL STUDENT,

Katharina Plasch

tel: +43-316-380-8646
e-mail:katharina.plasch(at)uni-graz.at

Katharina Plasch

Image result for Kurt Faber graz

Kurt Faber
Institute of Chemistry – Organic & Bioorganic Chemistry
Karl Franzens Universität Graz
Heinrichstrasse 28
8010 Graz

e-Mail: kurt.faber@uni-graz.at
phone: +43 316 380 5332
fax: +43 316 380 9840
web: http://biocatalysis.uni-graz.at

Kurt Faber, born 1953 in Klagenfurt (Carinthia/Austria), studied chemistry at the University of Graz, where he received his PhD in 1982. After a post-doctoral fellowship from 1982 to 1983 in St. John’s (Canada) he continued his career at the University of Technology in Graz, where he became associate professor in 1997. The following year he was appointed full professor at the University of Graz, where he since heads a research group devoted to the use of biocatalysts for the transformation of non-natural compounds. He was a visiting scientist at University of Tokyo (1987/1988), Exeter University (1990), University of Trondheim (1994), Stockholm University (2001) and University of Minnesota (2005).

Image result for Silvia M. Glueck graz

Silvia M. Glueck

Silvia M. Glueck, born 1973 in Bruck/Mur (Austria), studied Chemistry at the University of Graz, where she received her PhD under the supervision of Prof. K. Faber in 2004. From 2005 to 2006 she worked as a post-doctoral fellow with Prof. N. J. Turner at the University of Edinburgh and the University of Manchester (MIB). In 2007 she returned to the University of Graz to join Prof. W. Kroutil, and in 2008 she became Research Scientist at the Research Centre Applied Biocatalysis in the group of Prof. K. Faber. Her research interests are focusing on biocatalysis, molecular biology and organic synthesis.

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RESEARCHERS

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Pressurized CO₂ as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

K. Plasch, G. Hofer, W. Keller, S. Hay, D. J. Heyes, A. Dennig, S. M. Glueck and K. Faber, Green Chem., 2018, 20, 1754

DOI: 10.1039/C8GC00008E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

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For reproduction of material from all other RSC journals:
[Original citation] – Published by The Royal Society of Chemistry.

The Green ChemisTREE: 20 years after taking root with the 12 principles

green chemistry Comments Off

Apr 192018

The Green ChemisTREE: 20 years after taking root with the 12 principles

Green Chem., 2018, Advance Article
DOI: 10.1039/C8GC00482J, Critical Review

Hanno C. Erythropel, Julie B. Zimmerman, Tamara M. de Winter, Laurene Petitjean, Fjodor Melnikov, Chun Ho Lam, Amanda W. Lounsbury, Karolina E. Mellor, Nina Z. Jankovic, Qingshi Tu, Lauren N. Pincus, Mark M. Falinski, Wenbo Shi, Philip Coish, Desiree L. Plata, Paul T. Anastas
A broad overview of the achievements and emerging areas in the field of Green Chemistry.

The Green ChemisTREE: 20 years after taking root with the 12 principles

Hanno C. Erythropel,^a^b Julie B. Zimmerman,^a^b^c Tamara M. de Winter,^a^c Laurène Petitjean,^a^c Fjodor Melnikov,^a^c Chun Ho Lam,^a^c Amanda W. Lounsbury,^a^b Karolina E. Mellor,^a^c Nina Z. Janković,^a^b Qingshi Tu,^a^b Lauren N. Pincus,^a^c Mark M. Falinski,^a^b Wenbo Shi,^a^b Philip Coish,^a^c Desirée L. Plata^a^b and Paul T. Anastas*^a^b^c^d^e

Author affiliations

* Corresponding authors

^a Center for Green Chemistry and Green Engineering, Yale University, 370 Prospect Str., New Haven, USA
E-mail: paul.anastas@yale.edu

^b Dept. of Chemical and Environmental Engineering, Yale University, 10 Hillhouse Ave., New Haven, USA

^c School of Forestry and Environmental Science, Yale University, 195 Prospect Str., New Haven, USA

^d Dept. of Chemistry, Yale University, 225 Prospect Str., New Haven, USA

^e School of Public Health, Yale University, 60 College Str., New Haven, USA

Abstract

The field of Green Chemistry has seen many scientific discoveries and inventions during the 20 years since the 12 Principles were first published. Inspired by tree diagrams that illustrate diversity of products stemming from raw materials, we present here the Green ChemisTREE as a showcase for the diversity of research and achievements stemming from Green Chemistry. Each branch of the Green ChemisTREE represents one of the 12 Principles, and the leaves represent areas of inquiry and development relevant to that Principle (branch). As such, in this ‘meta-review’, we aim to describe the history and current status of the field of Green Chemistry: by exploring activity within each Principle, by summarizing the benefits of Green Chemistry through robust examples, by discussing tools and metrics available to measure progress towards Green Chemistry, and by outlining knowledge gaps, opportunities, and future challenges for the field.

Hanno C. Erythropel

Julie Zimmerman

ZIMMERMAN LAB

Professor of Chemical & Environmental Engineering & Forestry & Environmental Studies, julie.zimmerman@yale.edu

Tamara M. de Winter

Laurène Petitjean, laurene.petitjean@yale.edu

fjodor.melnikov@yale.edu

Image result for Paul T. Anastas yale Paul T. Anastas,

paul.anastas@yale.edu

//////////////Green ChemisTREE, green chemistry

Inspiring process innovation via an improved green manufacturing metric: iGAL

green chemistry Comments Off

Mar 292018

Inspiring process innovation via an improved green manufacturing metric: iGAL

Green Chem., 2018, Advance Article
DOI: 10.1039/C8GC00616D, Communication

Inspiring process innovation via an improved green manufacturing metric: iGAL

Frank Roschangar,*^a Yanyan Zhou,^b David J. C. Constable,^c Juan Colberg,^d David P. Dickson,^e Peter J. Dunn,^f Martin D. Eastgate,^g Fabrice Gallou,^h John D. Hayler,ⁱ Stefan G. Koenig,^j Michael E. Kopach,^k David K. Leahy,^l Ingrid Mergelsberg,^m Ulrich Scholz,ⁿ Austin G. Smith,^o Manuel Henry,^p Jason Mulder,^a Jörg Brandenburg,^q Juan R. Dehli,^q Daniel R. Fandrick,^a Keith R. Fandrick,^a Frieder Gnad-Badouin,^q Georg Zerban,^q Klaus Groll,^q Paul T. Anastas,^r Roger A. Sheldon^s^t and Chris H. Senanayake^a

Author affiliations

* Corresponding authors

^a Chemical Development, Boehringer Ingelheim Pharmaceuticals, Ridgefield, USA
E-mail: frank.roschangar@boehringer-ingelheim.com

^b Department of Statistics and Biostatistics, California State University East Bay, Hayward, USA

^c American Chemical Society Green Chemistry Institute, Washington District of Columbia 20036, USA

^d Pharmaceutical Sciences – Worldwide Research & Development, Pfizer, Groton, USA

^e Chemical Process R&D, Teva Pharmaceuticals, Malvern, USA

^f Pfizer, Sandwich, UK

^g Chemical and Synthetic Development, Bristol-Myers Squibb, New Brunswick, USA

^h Chemical & Analytical Development, Novartis Pharma, 4002 Basel, Switzerland

ⁱ API Chemistry, GlaxoSmithKline Medicines Research Centre, Stevenage, UK

^j Small Molecule Process Chemistry, Genentech, a Member of the Roche Group, South San Francisco, USA

^k Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, USA

^l Process Chemistry, Takeda Pharmaceuticals International, Cambridge, USA

^m Process Chemistry, Merck, Rahway, USA

ⁿ Chemical Development, Bayer AG – Pharmaceuticals, Wuppertal 42096, Germany

^o Process Development, Amgen, Thousand Oaks, USA

^p Chemical Process Development, Boehringer Ingelheim Pharma GmbH & Co. KG, 88307 Biberach an der Riß, Germany

^q Chemical Process Development, Boehringer Ingelheim Pharma GmbH & Co. KG, 55216 Ingelheim am Rhein, Germany

^r Yale University, New Haven, USA

^s Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg, South Africa

^t Delft University of Technology, 2628 BL Delft, Netherlands

Abstract

Following our goal to devise a unified green chemistry metric that inspires innovation in sustainable drug manufacturing across the pharmaceutical industry, we herein disclose joint efforts by IQ, the ACS GCI PR and academia, leading to the significantly improved ‘innovation Green Aspiration Level’ (iGAL) methodology. Backed by the statistical analysis of 64 drug manufacturing processes encompassing 703 steps across 12 companies, we find that iGAL affords an excellent proxy for molecular complexity and presents a valuable molecular weight-based ‘fixed’ goal. iGAL thereby accurately captures the impact of green process inventiveness and improvements, making it a useful innovation-driven green metric. We conclude by introducing the comprehensive, yet easy-to-use and readily adaptable Green Chemistry Innovation Scorecard web calculator, whose graphical output clearly and effectively illustrates the impact of innovation on waste reduction during drug manufacture.

Frank Roschangar

Frank Roschangar, PhD MBA

Director – Process Research & Global External Chemistry Management

Boehringer Ingelheim

Yanyan Zhou

Ange Zhou

Professor

California State University, East Bay

David Constable

David J. C. Constable

Juan Colberg

//////////////green manufacturing metric

http://www.rsc.org/suppdata/c8/gc/c8gc00616d/c8gc00616d1.pdf

Concise synthesis of ketoallyl sulfones through an iron-catalyzed sequential four-component assembly

green chemistry, spectroscopy, SYNTHESIS, Uncategorized Comments Off

Mar 092018

Concise synthesis of ketoallyl sulfones through an iron-catalyzed sequential four-component assembly

Green Chem., 2018, 20,973-977
DOI: 10.1039/C7GC03719H, Communication

Fuhong Xiao, Chao Liu, Dahan Wang, Huawen Huang, Guo-Jun Deng
A three starting material four component reaction (3SM-4CR) strategy is described to prepare [small beta]-acyl allylic sulfones from methyl ketones, sodium sulfinates and dimethylacetamide (DMA) in an iron-catalyzed oxidative system.

Concise synthesis of ketoallyl sulfones through an iron-catalyzed sequential four-component assembly

Fuhong Xiao,*^a Chao Liu,^a Dahan Wang,^a Huawen Huang^a and Guo-Jun Deng*^a

Author affiliations

* Corresponding authors

^a Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, Key Laboratory for Green Organic Synthesis and Application of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan 411105, China
E-mail: fhxiao@xtu.edu.cn, gjdeng@xtu.edu.cn

Abstract

A three starting material four component reaction (3SM-4CR) strategy is described to prepare β-acyl allylic sulfones from methyl ketones, sodium sulfinates and dimethylacetamide (DMA) in an iron-catalyzed oxidative system. In this process, DMA was used as a dual synthon to provide two carbons. A broad range of functional groups were tolerated in this reaction system.

1-phenyl-2-(tosylmethyl)prop-2-en-1-one (3ab)

43.2 mg, 72% yield).

1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2H), 7.68-7.65 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 6.25 (s, 1H), 6.02 (s, 1H), 4.35 (s, 2H), 2.39 (s, 3H).

13C NMR (100 MHz, CDCl3) δ 194.7, 144.9, 136.1, 135.8, 135.7, 133.9, 132.6, 129.8, 129.6, 128.3, 128.2, 57.7, 21.6.

HRMS calcd. for: C17H17O3S+ [M+H]+ 301.08929, found 301.08908