TAMAL ROY

ORGANIC CHEMISTRY, KTH-THE ROYAL INSTITUTE OF TECHNOLOGY, STOCKHOLM, SWEDEN

Email: tamal@kth.se � Web: https://www.kth.se/en/che/divisions/orgkem/organisk-kemi-1.18262

Objectives I wish to continue an effective career in research, teaching and leadership in Chemistry and in addition I have an aspiration to engage in interdisciplinary efforts that can utilize my expertise towards achieving global sustainability.

Area of Research Synthetic Organic Chemistry, Homogeneous and Heterogeneous Catalysis

Educational Background/Research Experience 2014-Present 'Development of new nucleophilic catalysts for enantioselective synthesis'

KTH-The Royal Institute of Tehnology Department of Chemistry, Organic Chemistry Under the supervision of Associate Professor Peter Diner

2009-2014 Doctor of Philosophy ‘Synthesis and Characterization of chiral homogeneous & heterogeneous metal complexes as active catalyst for the synthesis of epoxides and their derivatives’

Central Salt and Marine Chemicals Research Institute, Under the supervision of Dr. R. I. Kureshy Thesis submitted to Maharaja Krishnakumarsinhji Bhavnagar University PhD awarded on July, 2014 2007-2009 Master of Science with specialization in Organic Chemistry University of Delhi, Delhi, India 2004-2007 Bachelor of Science (Chemistry Hons.) Presidency College, University of Calcutta, Kolkata, India

The PhD Research Involved • Synthesis and characterization of chiral homogeneous and heterogeneous transition metal

complexes. • Asymmetric epoxidation of non-functionalized olefins. • Asymmetric Aminolytic and Hydrolytic Kinetic Resolution of terminal epoxides. • Asymmetric cycloaddition reaction of epoxide and CO2. • Asymmetric nitroaldol reaction of aldehydes and imines. • New synthetic methodology development of bioactive drug molecules. • Synthesis of novel catalyst for large scale production of industrially important fine chemicals

like styrene oxide, phenylethyl alcohol etc.

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Technical Expertise • Synthesis of organometallic reagents and catalysts • Synthesis under anhydrous conditions and use of glove box • High pressure synthesis • Proficient with numerous analytical instruments, including HPLC, GC, NMR, IR, UV, CD,

Polarimeter, • LC-MS, GC-MS.

Computational Skills Well versed in MS Office (Word, Excel, PowerPoint), and chemistry software such as Chemdraw, Mestre Nova, Mercury and Origin.

Fellowships/ Awards 1) Awarded Junior Research Fellowship (JRF) in Chemical Sciences through National Eligibility

Test conducted by Joint Council of Scientific and Industrial Research (CSIR)-University Grants Commission (UGC) in December 2008.

2) Qualified Graduate Aptitude Test in Engineering with 93.62 percentile score held on February 08, 2009 conducted by Indian Institute of Technology, Roorkee, India.

Research results – List of publications and patents 1. Reusable Chiral Dicationic Chromium(III) Salen Catalysts for Aminolytic Kinetic Resolution of

trans-Epoxides. Rukhsana I. Kureshy*, K. Jeya Prathap, Tamal Roy, Nabin Ch. Maity, Noor-ul H. Khan, Sayed H. R. Abdi and Hari C. Bajaj, Adv. Synth. Catal., 2010, 352, 3053-3060.

2. Asymmetric Hydrolytic Kinetic Resolution with Recyclable Macrocyclic CoIII–Salen Complexes: A Practical Strategy in the Preparation of (R)-Mexiletine and (S)-Propranolol. Arghya Sadhukhan, Noor-ul H. Khan*, Tamal Roy, Rukhsana I. Kureshy, Sayed H. R. Abdi and Hari C. Bajaj, Chem. Eur. J., 2012, 18, 5256-5260.

3. Reusable chiral macrocyclic Mn(III) salen complexes for enantioselective epoxidation of nonfunctionalized alkenes. Rukhsana I. Kureshy*, Tamal Roy, Noor-ul H. Khan, Sayed H.R. Abdi, Arghya Sadhukhan and Hari C. Bajaj, J. Catal., 2012, 286, 41-50.

4. Immobilized dimeric chiral Mn(III) salen complex on short channel ordered mesoporous silica as an effective catalyst for the epoxidation of non-functionalized alkenes. Tamal Roy, Rukhsana I. Kureshy*, Noor-ul H. Khan, Sayed H.R. Abdi, Arghya Sadhukhan and Hari C. Bajaj, Tetrahedron, 2012, 68, 6314-6322.

5. Asymmetric cycloaddition of CO2 and an epoxide using recyclable bifunctional polymeric Co(III) salen complexes under mild conditions. Tamal Roy, Rukhsana I. Kureshy*, Noor-ul H. Khan, Sayed H.R. Abdi and Hari C. Bajaj, Catal. Sci. Technol., 2013, 3, 2661-2667.

6. Enantioselective Henry and aza-Henry Reaction in the synthesis of (R)-tembamide using Efficient Recyclable Polymeric Cu(II) Complexes as catalyst. Anjan Das, Manoj Chaudhary, Rukhsana I. Kureshy*, Tamal Roy, Noor-ul H. Khan, Sayed H. R. Abdi and Hari C. Bajaj, ChemPlusChem, 2014, 79, 1138-1146.

7. Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(III)-salen complexes: A practical strategy in the preparation of (S)-Metoprolol, (S)-Toliprolol and (S)-Alprenolol: Computational rationale for enantioselectivity. Tamal Roy, Sunirmal Barik, Manish Kumar,

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Rukhsana I. Kureshy*, Biswajit Ganguly*, Noor-ul H. Khan, Sayed H.R. Abdi, and Hari C. Bajaj, Catal. Sci. Technol., 2014, 4, 3899-3908.

8. Immobilization of cationic Al(III) salen in the interlayers of montmorillonite clay for the synthesis of cyclic carbonate. Shailesh Verma, Rukhsana I. Kureshy, Tamal Roy, Manish Kumar, Anjan Das, Noor-ul H. Khan, Sayed H.R. Abdi and Hari C. Bajaj, Catal. Commun., 2015, 61, 78-82.

9. Ordered short channel mesoporous silica modified with 1,3,5-triazine–piperazine as a versatile recyclable basic catalyst for cross-aldol, Knoevenagel and conjugate addition reactions with isatins. Naveen Gupta, Tamal Roy, Debashis Ghosh, Sayed H. R. Abdi, Rukhsana I. Kureshy, Noor-ul H. Khan and Hari C. Bajaj , 2015, 5, 17843-17850.

10. Self-supported chiral polymeric Mn(III) salen complexes as highly active and recyclable catalyst for epoxidation of non-functionalized olefins. Tamal Roy, Rukhsana I. Kureshy*, Noor-ul H. Khan, Sayed H.R. Abdi and Hari C. Bajaj, ChemPlusChem, 2015, 5, 1038-1044.

11. Hydrogenation of styrene oxide forming 2-phenyl ethanol. Hari C. Bajaj, Sayed H. R. Abdi, Rukhsana I. Kureshy, Noor-ul H. Khan, Asif A. Dabbawala, Tamal Roy, US20140330047.

12. Recyclable chiral catalyst for asymmetric nitroaldol reaction and process for the preparation thereof. Rukhsana I. Kureshy, Noor-ul H. Khan, Sayed H. R. Abdi, Hari C. Bajaj, Tamal Roy, Anjan Das, WO 2014118799 A1.

13. An Improved process for the synthesis of epoxides from olefins using a recyclable organic promoter. Rukhsana I. Kureshy, Noor-ul H. Khan, Sayed H. R. Abdi, Hari C. Bajaj, Tamal Roy, Minaxi S. Maru, 0053NF2014.

Poster Presented at Confereces: 1. 13th CRSI & 5th RSC-CRSI Symposium in Chemistry NISER & KIIT University, Bhubaneswar,

India, Feb 4-6, 2011. 2. 18th International Conference (Post ISCBC-2012), Institute of Advanced Study in Science &

Technology (IASST), Guwahati, India 3. 21st national symposium on catalysis, "catalysis for sustainable development", February 10-

13, 2013, IICT, Hyderabad, India.

Personal Details: Date of Birth: 17th February, 1987 Permanent Address: Vill + P.O- Galigram, Dist.-Burdwan, West Bengal, India-713406 Present Address: DIMC, CSMCRI, G. B. Marg, Bhavnagar, Gujarat, India-364002 Marital Status: Single Extra-Curricular Activities: Held editorial post for two years in school magazine Research results – Summary of research work Major achievements: successful completion of PhD in chemistry, with many high quality publications in international journals (see above list); presentation at a recent international conference (ISCB-2012).

The central tenet of my PhD work revolved around the use recyclable homogeneous and heterogeneous catalysts combined with the synthesis of important drug molecules. Our main experimental aims were to develop catalysts that are economical, recyclable as well as scalable. In our quest for the development of recyclable catalysts under homogeneous systems, one way is to increase the molecular weight of the catalyst so that it has lower solubility in some non-polar

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solvents, facilitating product isolation and catalyst recovery, which in turn makes the post reaction work up much more convenient than conventional methods. In contrary catalysts could be made recyclable under heterogeneous condition with the use of a suitable solid support such as mesoporous silica.

I was able to achieve excellent results for a number of different types of reaction. The research gave me skills in synthetic chemistry: reaction design, handling of chemicals, use of laboratory equipment, isolation and purification techniques, spectroscopic skills, data analysis, record keeping, critical appraisal and ability to propose research ideas. In addition, I have gained skills in scientific writing, scientific ethics, time management, working independently and in a team, and in basic health and safety.

The following is a summary of my research work.

A. Preparation of chiral epoxides from non-functionalized olefins using new catalysts

In the beginning of my research, I synthesized new monomeric and dimeric macrocyclic salen ligands and their manganese (III) complexes (Figure 1). These complexes were then investigated as catalysts for enantioselective epoxidation of olefins in the presence of inexpensive pyridine-N-oxide as an additive and buffered sodium hypochloride as an oxidant (Scheme 1).

Figure 1 Catalysts with built-in crown ether-like motif in chiral macrocyclic Mn(III) salen complexes.

These Mn(III) salen complexes turned out to be one of the most efficient recyclable systems reported so far in the literature. The interesting feature of this dimeric salen complex lies in its inherent tendency to precipitate in a nonpolar solvent like n-hexane as well as its better ability to transfer active oxidant from aqueous layer to organic layer due to crown like motif. The catalyst was recovered and worked well in up to six further cycles without any loss in reactivity. Moreover, the active Mn(III) macrocyclic dimeric salen complex retained its performance even at multi-gram level.

Scheme 1 Enantioselective epoxidation of non-functionalized olefins using chiral macrocyclic Mn(III) salen complexes.

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Chiral dimeric Mn(III) salen complex immobilized into disc like mesoporous silica of short channel was used for the enantioselective epoxidation of various non-functionalized alkenes, which showed activity and enantioselectivity comparable with dimeric macrocyclic homogeneous catalysts. The present support due to large pore size and short channel length was apparently responsible for least diffusional constrains in accessing the supported Mn(III) salen sites, thereby giving high activity and enantioselectivity even for relatively bulkier substrates such as indene and chromenes and the catalyst was easily recycled six times without any loss in its performance. This protocol with catalyst was used for the synthesis of (S)-Levchromakalim, a potent hypertensive drug in single step in good yield and enantioselectivity by using 6-cyano-2,2-dimethylchromene oxide (Scheme 2).

Scheme 2 Application of heterogeneous dimeric Mn(III) salen complex in the synthesis of (S)-Levchromakalim.

B. Asymmetric cycloaddition of epoxide and CO2 using bifunctional chiral catalyst

Due to its high abundance and inexpensive, renewable, non-toxic and non-flammable nature, CO2 is ideal for use as the starting material for valuable chemicals. In this direction utilization of carbon dioxide for kinetic resolution (KR) of racemic epoxides is a 100%-atom economical and environmentally friendly reaction to produce highly valuable enantiopure epoxides and cyclic carbonates in one go (Scheme 3). We have designed and synthesized a series ofrecyclable bifunctional polymeric Co(III) salen complexes based on a triazine–piperazine core and utilized them in the asymmetric cycloaddition of various terminal epoxides with CO2at atmospheric pressure and at low temperatures (20 οC to 0 οC). The best catalyst, Co(III)CCl3COO, gave optically active propylene carbonate with up to 74% ee under mild conditions without the use of any external Lewis base as an additive. Although the catalyst performance in the present report was on a par with previously reported catalysts, efficient catalyst recyclability (10 cycles) without any loss in activity or enantioselectivity is the most striking feature of the present catalyst design. The present catalyst framework with some modifications in the catalyst core reaction site is expected to enhance the ee of cyclic carbonates to the desired level for their commercial application.

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Scheme 3 Asymmetric Cycloaddition of CO2 and racemic epoxiode using bifunctional Co(III) salen complexes.

C. Asymmetric hydrolytic kinetic resolution of terminal epoxides using polymeric catalyst

By the year 2017, the global market for chiral technology is expected to reach $5.1 billion (according to a report by Global Industry Analysts Inc., April 2012) and to meet ever increasing demand for optically pure molecules in the pharmaceutical sector, the development of highly active and enantioselective catalysts is crucial. For example, medicines for stress related ailments and cardiovascular drugs can be synthesized via chiral epoxides. These chiral epoxides can be obtained by the hydrolytic kinetic resolution (HKR) of inexpensive racemic epoxides. In this direction a series of chiral polymeric Co(III) salen complexes based on a number of achiral and chiral linker were synthesized and their catalytic performances were assessed in asymmetric hydrolytic kinetic resolution of terminal epoxides. The effect of the linker were judiciously studied and it was found that in case of chiral BINOL based polymeric salen complex 7, there was certain enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yield of the unreacted epoxide (up to 46%) along with high enantioselectivity (up to >99%) was obtained in most of the cases using catalyst 7 (Scheme 4). Further studies exhibited that the catalyst 7 was recyclable for 6 cycles under the present reaction condition without any significant loss in activity and enantioselectivity. To show the practical applicability of the above synthesized catalyst we have carried out synthesis of some potent chiral β-blockers [(S)-Metoprolol, (S)-Toliprolol and (S)-Alprenolol] using complex 7 in moderate yield and high enantioselectivity.

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Scheme 4 Asymmetric hydrolytic kinetic resolution of racemic epoxiode using polymeric Co(III) salen complexes

Independent thinking, leadership qualities, and capacity to transfer knowledge

In 2009, I was entrusted to develop recyclable metal based catalysts for asymmetric epoxidation of non-functionalized olefins. Jacobsen and Katsuki type of manganese salen complexes are ground breaking catalysts for the production of chiral epoxides from non-functionalized olefins but the recyclability of these catalysts was a major issue. Moreover under biphasic reaction condition Jacobsen type salen complex require an expensive version of lyophobic N-oxides. To overcome these drawbacks I have designed and synthesized chiral macrocyclic Mn(III) salen complexes with built in crown ether type motif. Fine tuning in catalyst solubility with increase molecular weight resulting in better recyclability as well as ability to work even with inexpensive lyophilic PyNO makes the current catalyst system one of the most effective one. With this success in hand I was given full freedom from my supervisor to synthesize novel metal based homogeneous as well as heterogeneous catalysts for the synthesis of highly valuable chiral epoxides and their derivatives along with their application in the synthesis of pharmaceutically important targets.

Later on in 2012, I was given an important task by my research mentor to develop catalysts for asymmetric cycloaddition reaction of epoxide and CO2 as a part of an ambitious network project of CSIR-India on CO2 utilization. I have developed a bifunctional catalyst for this purpose and the results have been published in the form of a full paper.

I have demonstrated a high level of research competency during my PhD and have shown that I can take a research idea and turn it in to a successful conclusion, obtaining excellent results. I have contributed to the writing of several publications of his work and this demonstrates my ability to transfer knowledge and to develop skills as an independent academic. I have interacted with many different researchers to discuss my science and have started to develop my own research ideas.

After the second year of commencing my PhD studies, I was entrusted to take lead role in training my younger colleagues. I gave classes on instrumentation and research methodology. These were based on the handling and maintenance of sophisticated instruments (for example, a polarimeter, glove box, high performance liquid chromatography, gas chromatography (GC) and a high pressure reactor), the prediction of structures of organic compounds by NMR, UV, and IR spectroscopy, and by GC- and LC-mass spectrometry, together with reaction set up and research

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paper writing. I was also involved with guiding younger colleagues in designing new chiral catalysts for several asymmetric organic transformations. My current research work is based on CO2 utilization and asymmetric C-C bind formation reaction. I am simultaneously working on it as well as helping my younger colleagues working in this direction. I have also experience in industrial scale production of styrene oxide. Know-how of this process have been transferred to two national fine chemicals industry where I have taken an active part in the demonstration of the process.

References Dr. Rukhsana I. Kureshy Senior Principal Scientist (Ph.D. Supervisor) CSIR-Central Salt and Marine Chemical Research Institute Bhavnagar, Gujarat, India- 364 002 Phone: +91 278 2567760 Ext 7130 Fax: +91 278 2567562 Email: rukhsana93@yahoo.co.in Dr. Noor-ul H. Khan Principal Scientist CSIR-Central Salt and Marine Chemical Research Institute Bhavnagar, Gujarat, India- 364 002 Phone: +91 278 2567760 Ext 7130 Fax: +91 278 2567562 Email: nhkhan@csmcri.org Associate Prof. Peter Dinér KTH-The Royal Institute of Technology, Department of Chemistry, Organic Chemistry. Stockholm, SE-10044 Fax: ++46 (0)8-7912333, Email: diner@kth.se

I hereby declare that all the information furnished by me above is true to the best of my knowledge.

Place: Stockholm, Sweden

Date: 29th October, 2015 (Tamal Roy)