We developed a sustainable three-component reductive amination protocol for the chemoselective coupling of optically active functionally rich donor–acceptor carbonyl-cyclopropanes with various amines under 10 mol % of diphenyl phosphate in the presence of Hantzsch ester as a hydride source. The catalytic selective reductive C–N coupling has wide advantages like no epimerization, no ring opening, large substrate scope, generating only mono N-alkylation products and simultaneously resulting in chiral cyclopropane-containing amines possessing many applications in the medicinal chemistry.
Pharmaceutically and structurally important methanobenzo[7]annulenes were synthesized in very good yields with excellent enantio‐ and diastereoselectivities through an unprecedented organocatalytic formal [3+2] cycloaddition from readily available 2‐alkyl‐3‐hydroxynaphthalene‐1,4‐diones and alkyl vinyl ketones.
A Ca(OTf)2- and self-promoted ynone–amidine atom-economic formal [4 + 2]-cycloaddition of various ynones with amidines is reported for the construction of highly functionalized tricyclic azepines. High reaction rate, ease of operation, and high product selectivity with wide substrate scope are the key advantages of the present annulation protocol.
Pharmaceutically and structurally important methanobenzo[7]annulenes were synthesized in very good yields with excellent enantio‐ and diastereoselectivities through an unprecedented organocatalytic formal [3+2] cycloaddition from readily available 2‐alkyl‐3‐hydroxynaphthalene‐1,4‐diones and alkyl vinyl ketones.
An ideal stereo selective insertion of in situ generated benzynesintolawsones through domin oformal[2+2]-cyclo addition followed by rearrangement is dis-closed.The reaction allowed for the preparation of biolog-icallyimportantbenzannulated bicyclo[3.3.0]octanesin good yield sandwi the excellent selectivities by using simple substrates and conditions.
Multicatalysis cascade process for the synthesis of highly substituted chiral building blocks is presented based on the cascade three-component reductive alkylation’s platform. Herein, we developed the high-yielding alkylation of a variety of CH-acids with (R)- glyceraldehyde acetonide/(S)-Garner aldehyde and Hantzsch ester through amino acid-catalyzed TCRA reaction without racemization at the α-position to carbonyl. Direct sequential combination of the L-proline-catalyzed TCRA reaction with other reactions like cascade alkylation/ketenization/ esterification, alkylation/ketenization/esterification/alkylation, Brønsted acid catalyzed cascade hydrolysis/lactonization/esterification, hydrolysis/esterification, hydrolysis/oxy-Michael/dehydration, and Robinson annulation of CH-acids, chiral aldehydes, Hantzsch ester, diazomethane, methyl vinyl ketone, various active olefins, and acetylenes furnished the highly functionalized chiral building blocks in good to high yields with excellent diastereoselectivities. In this context, many of the pharmaceutically applicable chiral building blocks were prepared via MCC reactions.
Creating sequential one-pot combinations of multi-component reactions (MCRs) and multi-catalysis cascade (MCC) reactions is a challenging task that has already emerged as a new technology in synthetic organic chemistry. Through one-pot sequential combination of MCRs/MCC reactions, the chemical products (fine chemicals, agrochemicals and pharmaceuticals) that add value to our lives can be produced with less waste and greater economic benefits. Within this emerging area, we describe our recent developments and designs for sequential one-pot MCRs/MCC reactions to facilitate their realization as biomimetics in organic chemistry.
A general, sustainable and practical process for the sequential cascade one-pot synthesis of library of highly substituted push−pull olefins, phenols and 2-methyl-2H-chromenes was reported through multi catalysis cascade (MCC) reactions. Direct sequential one-pot combination of amine- or amino acid-catalyzed cascade Knoevenagel/Michael/aldol condensation/decarboxylation with other reactions like amine- or amino acid-catalyzed cascade Claisen−Schmidt/iso-aromatization, Claisen−Schmidt/isomerization, Claisen−Schmidt/iso-aromatization/isomerization, Michael addition, Claisen−Schmidt/Michael, ruthenium-base-silica-catalyzed ring closing metathesis/base-induced ring-opening/benzylic oxidation/[1,7]-sigmatropic hydrogen shift, or ruthenium-base-heat-catalyzed ring closing metathesis/base-induced ring-opening/[1,7]-sigmatropic hydrogen shift reactions of alkyl acetoacetates, a variety of aldehydes and alkyl halides furnished the highly functionalized push−pull olefins, phenols and 2-methyl-2H-chromenes with high yields. The yields and regioselectivities were good to excellent. Evidence for a new reaction pathway involving in situ formation of novel push−pull dienamines under amine- or amino acid-catalysis is presented along with examples demonstrating the amenability of the process to MCC chemistry.
A practical and sustainable chemical process for the synthesis of highly substituted aldol↔lactol products was achieved for the first time through the asymmetric Barbas-List aldol (BLA) reaction of 2-hydroxybenzaldehydes with acetone in the presence of a catalytic amount of trans-4-OH-L-proline.
1. D. B. Ramachary, Adluri B. Shashank, and S. Karthik, An Organocatalytic Azide-Aldehyde [3+2] Cycloaddition: High-Yielding Regioselective Synthesis of 1,4-Disubstituted 1,2,3-Triazole, Angew. Chem. Int. Ed. 2014, 53, 10420-10424. [Most accessed Article in August-2014]
2. Sequential One-Pot Combination of Multi-Component and Multi-Catalysis Cascade Reactions: An Emerging Technology in Organic Synthesis Org. Biomol. Chem., 2011, 9, 1277-1300 is featured in top 1% of the most highly cited articles published in published in the latest Impact Factor window (2011-2012).
3. D. B. Ramachary, P. Srinivasa Reddy and M. Shiva Prasad, Neighboring ortho-Hydroxyl Group Directed Catalytic Asymmetric Triple Domino Reactions of Acetaldehyde with (E)-2-(2-Nitrovinyl)Phenols, Eur. J. Org. Chem., 2014, 3076-3081. [Top ten Most accessed Article in April-2014]
4. D. B. Ramachary and Y. V. Reddy, Dienamine-Catalysis: An Emerging Technology in Organic Synthesis, Eur. J. Org. Chem. 2012, 865-887
5. Pfizer Worldwide Research and Development Company Demonstrated the Pilot Plant (15 kg Scale) Synthesis of Active Pharmaceutical Ingredient, Filibuvir (Hepatitis C Virus Polymerase Inhibitor) by using recently our Laboratory Developed Three-Component Reductive Alkylation (TCRA) Reaction as key Coupling Protocol.
Semi-batch addition of β-keto-lactone (2) to aldehyde (3) and HEH (12):
6. D. B. Ramachary, M. Shiva Prasad, S. Vijaya Laxmi and R. Madhavachary, Asymmetric Synthesis of Drug-like Spiro[chroman-3,3'-indolin]-2'-ones through Aminal-catalysis, Org. Biomol. Chem., 2014, 12, 574-580. [Top ten Most accessed Article in 12/2013]
7. Dr. R. Sakthidevi has Won the Lilly-2013 Outstanding Thesis Award for her Studies on the Observation of Neighboring Group Participation in Organocatalytic Asymmetric Reactions.
8. D. B. Ramachary, Ch. Venkaiah, and P. M. Krishna, Stereoselective Synthesis of Five-membered Spirooxindoles through Tomita Zipper Cyclization, Org. Lett., 2013, 15, 4714-4717. [Top 20 Most downloaded article in September-2013]
9. D. B. Ramachary and Adluri B. Shashank, Organocatalytic Triazole Formation, Followed by Oxidative Aromatization: Regioselective Metal-free Synthesis of Benzotriazoles, Chem. Eur. J., 2013, 19, 13175-13181. [Top ten Most accessed Article in August-2013]
10. D. B. Ramachary and Y. V. Reddy, Dienamine-Catalysis: An Emerging Technology in Organic Synthesis, Eur. J. Org. Chem. 2012, 865-887. [Top ten Most accessed Article in 9/2012-8/2013]
11. B.M Birla Science Prize distribution ceremony (Video)
12. News on B. M. Birla Science Prize in Chemical Sciences-2011
13. D. B. Ramachary and Y. V. Reddy, Dienamine-Catalysis: An Emerging Technology in Organic Synthesis, Eur. J. Org. Chem. 2012, 865-887. [Top ten Most accessed Article in November-2012]
14. Our Recent Review on Dienamine-Catalysis: An Emerging Technology in Organic Synthesis by D. B. Ramachary and Y. V. Reddy is Now Freely Available Top-25 Most-accessed Article Through Eur. J. Org. Chem. 2012, 865-887
15. Dr. Y. V. Reddy has Won the Lilly-2012 Outstanding Thesis Award for his Studies on the Application of TCRA Reaction in Synthetic and Medicinal Chemistry
16. D. B. Ramachary, R. Sakthidevi and K. S. Shruthi, Asymmetric Supramolecular-catalysis: A Bio-inspired Tool for the High Asymmetric Induction in the Enamine-based Michael Reactions, Chem. Eur. J., 2012, 18, 8008-8012. [Top Ten Most accessed Article in June/2012]
17. The Importance of Asymmetric Supramolecular Catalysis is Highlighted in The PHARMABIZ
18. The Importance of Novel Technology Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions is Highlighted in The Reachout Hyderabad
19. The Importance of Novel Technology Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions is Highlighted in The PHARMABIZ
20. The Importance of New Technology Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions is Disclosed in The Indiamart SME news
21. News on Importance of New Technology Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions is Disclosed in The The Hans India
22. News on Importance of New Chemical Technology Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions is Disclosed in The The Asian Age
23.News on Importance of New Chemical Tool Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions by Senior Editor, Deccan Chronicle, Syed Akbar, in his Blog
24. News on Importance of New Chemical Tool Asymmetric Supramolecular Catalysis for the Understanding Unstable Pre- or Post-Transition States of Asymmetric Reactions by Syed Akbar, Senior Editor in Deccan Chronicle
25. D. B. Ramachary and Y. V. Reddy, Dienamine-Catalysis: An Emerging Technology in Organic Synthesis, Eur. J. Org. Chem. 2012, 865-887. [Most accessed Article in 5/2011-4/2012]
26. D. B. Ramachary and Y. V. Reddy, Dienamine-Catalysis: An Emerging Technology in Organic Synthesis, Eur. J. Org. Chem. 2012, 865-887. [Top ten Most accessed Article in Feb-2012]
27. Dr. Sangeeta Jain has Won the Academic Excellence Award from Madhya Pradesh Health University, Jabalpur for her recent review on Sequential Combination of Multi-catalysis/Multi-component Reactions
28. D. B. Ramachary and Y. V. Reddy, Dienamine-Catalysis: An Emerging Technology in Organic Synthesis, Eur. J. Org. Chem. 2012, 865-887. [Top ten Most accessed Article in December 2011]
29. Dr. M. Kishor has Won the 1st Prize of Lilly-2011 Outstanding Thesis Award for his Studies on Discovery of TCRA Reactions.
30. D. B. Ramachary, K. Ramakumar, A. Bharanishashank, and V. V. Narayana, Sequential One-Pot Combination of Multi Reactions Through Multicatalysis: A General Approach to Rapid Assembly of Functionalized Push−Pull Olefins, Phenols, and 2-Methyl-2H-Chromenes, J. Comb. Chem., 2010, 12 (6), 855-876, [Top 20 Most downloaded Articles over the last 12 months]
31. D. B. Ramachary and K. Ramakumar, Direct Organocatalytic Asymmetric Approach to the Baylis-Hillman-Type Products via Push-Pull Dienamine Platform, Eur. J. Org. Chem. 2011, 2599-2605. [Top ten Most accessed Article in May 2011]
32. D. B. Ramachary and K. Ramakumar, Direct Organocatalytic Asymmetric Approach to the Baylis-Hillman-Type Products via Push-Pull Dienamine Platform, Eur. J. Org. Chem. 2011, 2599-2605. [Top ten Most accessed Article in April 2011]
33. D. B. Ramachary and Sangeeta Jain, Sequential One-Pot Combination of Multi-Component and Multi-Catalysis Cascade Reactions: An Emerging Technology in Organic Synthesis, Org. Biomol. Chem., 2011, 9, 1277-1300, [Top ten Most accessed Article in March 2011]
34. D. B. Ramachary, M. Shiva Prasad and R. Madhavachary, A General Approach to High-yielding Asymmetric Synthesis of Chiral 3-Alkyl-4-Nitromethylchromans via Cascade Barbas-Michael and Acetalization Reactions, Org. Biomol. Chem., 2011, 9, 2715-2721. [Top ten Most accessed Article in March 2011]
35. D. B. Ramachary and Sangeeta Jain, Sequential One-Pot Combination of Multi-Component and Multi-Catalysis Cascade Reactions: An Emerging Technology in Organic Synthesis, Org. Biomol. Chem., 2011, 9, 1277-1300, [Number One in Top ten Most accessed Articles in February 2011]
36. News on Importance of Sequential One-Pot Combination of Multi-Component and Multi-Catalysis Cascade Reactions: An Emerging Technology in Organic Synthesis Highlighted in University of Hyderabad SPOTLIGHTS
37. News on Importance of Sequential One-Pot Combination of MCR’s and MCC Reactions in Synthetic Organic/Pharmaceutical Chemistry by Syed Akbar, Senior Editor in Deccan Chronicle
38. Highlights on our Recent Emerging Area Article of Sequential One-Pot Combination of MCR and MCC Reactions by Lorena Tomas Laudo, Deputy Editor of OBC in Organic & Biomolecular Chemistry Blog
39. D. B. Ramachary and Sangeeta Jain, Sequential One-Pot Combination of Multi-Component and Multi-Catalysis Cascade Reactions: An Emerging Technology in Organic Synthesis, Org. Biomol. Chem., 2011, 9, 1277-1300, [Highlighted on Journal Cover Page] [Top ten Most accessed Article in December 2010]
40. D. B. Ramachary, K. Ramakumar, A. Bharanishashank, and V. V. Narayana, Sequential One-Pot Combination of Multi Reactions Through Multicatalysis: A General Approach to Rapid Assembly of Functionalized Push−Pull Olefins, Phenols, and 2-Methyl-2H-Chromenes, J. Comb. Chem., 2010, 12 (6), 855-876, [Most read Article ]
41. D. B. Ramachary, Rumpa Mondal, C. Venkaiah, Rapid Synthesis of Functionalized Indenes, Triazoles, and Glucocorticoid Receptor Modulators by Sequential Multicatalysis Cascade Reactions, Eur. J. Org. Chem. 2010, 3205-3210, [One of the Top ten Most accessed Article in 05/2010 from Eur. J. Org. Chem.]
42. D. B. Ramachary and R. Sakthidevi, Sequential Combination of Michael and Acetalization Reactions: Direct Catalytic Asymmetric Synthesis of Functionalized 4-Nitromethyl-Chromans as Drug Intermediates, Org. Biomol. Chem., 2010, 8, 4259-4265, [One of the Top ten Most downloaded OBC article in August 2010]
43. D. B. Ramachary, Rumpa Mondal and C. Venkaiah, Rapid Two-Step Synthesis of Drug-Like Polycyclic Substances by Sequential Multi-Catalysis Cascade Reactions, Org.Biomol. Chem., 2010, 8, 321-325. [One of the Top ten Most downloaded OBC article in January 2010]
44. D. B. Ramachary, V. V. Narayana, M. Shiva Prasad and K. Ramakumar, High-Yielding Synthesis of Nefopam Analogues (Functionalized Benzoxazocines) by Sequential One-Pot Cascade Operations, Org. Biomol. Chem., 2009, 7, 3372-3378. [One of the Top ten Most downloaded OBC article in August 2009]
45. D. B. Ramachary and R. Sakthidevi, Direct Catalytic Asymmetric Synthesis of Highly Functionalized 2-Methylchroman-2,4-diols via Barbas-List Aldol Reaction, Chem. Eur. J., 2009, 15, 4516-4522. [One of the Top ten Most accessed Chem. Eur. J, article in March 2009]
46. D. B. Ramachary and R. Sakthidevi, Direct Catalytic Asymmetric Synthesis of Highly Functionalized 2-Methylchroman-2,4-diols via Barbas-List Aldol Reaction, Chem. Eur. J., 2009, 15, 4516-4522. [One of the Top ten Most accessed Chem. Eur. J, article in April 2009]
47. D. B. Ramachary, K. Ramakumar and V. V. Narayana, Amino Acid-Catalyzed Cascade [3+2]-Cycloaddition/Hydrolysis Reactions Based on the Push-Pull Dienamine Platform: Synthesis of Highly Functionalized NH-1,2,3-Triazoles, Chem. Eur. J., 2008, 14, 9143-9147. [One of the Top ten Most accessed Chem. Eur. J. article in September 2008]
48. D. B. Ramachary, V. V. Narayana and K. Ramakumar, A New One-Pot Synthetic Approach to the Highly Functionalized (Z)-2-(Buta-1,3-dienyl)phenols and 2-Methyl-2H-chromenes: Use of Amine, Ruthenium and Base-Catalysis, Eur. J. Org. Chem., 2008, 3907-3911. [One of the Top ten Most accessed Eur. J. Org. Chem., article in July 2008]
49. D. B. Ramachary, M. Kishor and Y. Vijayendar Reddy, Development of Pharmaceutical Drugs, Drug Intermediates and Ingredients by Using Direct Organo-Click Reactions, Eur. J. Org. Chem., 2008, 975-993. [One of the Top 25 Most accessed Eur. J. Org. Chem., article in 2008 and 2009]
50. D. B. Ramachary, G. Babul Reddy and Rumpa Mondal, A new organocatalyst for Friedel-Crafts alkylation of 2-naphthols with isatins: application of an organo-click strategy for the cascade synthesis of highly functionalized molecules, Tetrahedron Lett., 2007, 48, 7618-7623. (One of the TOP25 Hottest Articles - downloaded during October, November and December-2007)
51. D. B. Ramachary and G. Babul Reddy, Towards Organo-Click Reactions: Development of Pharmaceutical Ingredients by Using Direct Organocatalytic Bio-Mimetic Reductions, Org. Biomol. Chem., 2006, 4, 4463-4468. [One of the Most downloaded OBC article in December 2006]
52. D. B. Ramachary and Rumpa Mondal, Direct Organocatalytic Hydroalkoxylation of a,b-Unsaturated Ketones, Tetrahedron Lett., 2006, 47, 7689-7693. (One of the TOP25 Hottest Articles - downloaded during October, November and December-2006)
53. D. B. Ramachary, M. Kishor and K. Ramakumar, A Novel and Green Protocol for Two-Carbon Homologation: A Direct Amino Acid/K2CO3-Catalyzed Four-Component Reaction of Aldehydes, Active Methylenes, Hantzsch Esters and Alkyl Halides, Tetrahedron Lett., 2006, 47, 651-656. [Highlighted on Journal Cover Page]
54. D. B. Ramachary and Carlos F. Barbas III, Towards Organo-Click Chemistry: Development of Organocatalytic Multicomponent Reactions Through Combinations of Aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen Cycloaddition Reactions, Chem. Eur. J., 2004, 10, 5323-5331. [Most requested article in 2005 according to CAS] and [Highlighted on Journal Cover Page]
55. D. B. Ramachary, K. Anebouselvy, Naidu S. Chowdari and Carlos F. Barbas III, Direct Organocatalytic Asymmetric Hetero-Domino Reactions: The Knoevenagel/Diels-Alder/Epimerization (K-DA-E) Sequence for the Highly Diastereoselective Synthesis of Symmetrical and Non-Symmetrical Synthons of Benzoannelated Centropolyquinanes, J. Org. Chem., 2004, 69 (18), pp 5838-5849 [Most requested article in 2004 according to ACS]
