Illuminating a Path4914. Copyright 2016 Wiley for Organic Synthesis Towards Sustainability. No One Said It Would Be Easy…

Abstract

A personalized account is presented describing some of the stories behind the scenes in efforts to convert organic chemistry into a more sustainable discipline. These are part of a group ‘crusade’ started almost 15 years ago aimed at providing technologies illustrative of how key reactions used today can be ‘faster, better, cheaper’ when run in recyclable water. Hence, the option now exists to do organic synthesis in a far more environmentally responsible fashion. By contrast, most of organic chemistry developed over the past 200 years that relies on organic solvents continues to generate enormous amounts of pollution, while depleting finite petroleum reserves and our supplies of many precious and base metals. Making the switch to water, Nature’s chosen reaction medium, akin to that in which bio-catalysis is typically performed, is inevitable.

1 The Story Begins: A Different Type of Prejudice

2 Are We up to the Challenge? Too Late Now…

3 ‘Impossible’ Reactive Metal Chemistry in Water

4 Didn’t I Once Say: ‘It’s All about the Ligand’?

5 What Happens When Our Supply of Palladium Runs Out?

6 What Are the Implications from These Tales for Today and Tomorrow?

7 What Is the ‘Broader Impact’ of This Work?

8 The Bottom Line…

Key words

sustainability - green chemistry - chemistry in water - chemo-catalysis - ppm level Pd

Publication History

Received: 30 December 2020

Accepted after revision: 15 April 2021

Article published online:
15 April 2021

• References

• 1 Cortes-Clerget M, Yu T.-Y, Kincaid JR. A, Walde P, Gallou F, Lipshutz BH. Chem. Sci. 2021; 12 in press; DOI:
• 2 See, for example: de Bernardins V, Guerard-Helaine C, Darli E, Bastard K, Helaine V, Mariage A, Petit J.-L, Poupard N, Sanchez-Moteno I, Stam M, Gefflaut T, Salanoubat M, Lemaire M. Green Chem. 2017; 19: 519
• 3 See, for example: Dilauro G, Quivelli AF, Vitale P, Caprioti V, Perna FM. Angew. Chem. Int. Ed. 2019; 58: 1799
• 4a Devine PN, Howard RM, Kumar R, Thompson MP, Truppo MD, Turner NJ. Nat. Rev. Chem. 2018; 2: 409
• 4b Hughes GJ, Lewis JC. Chem. Rev. 2018; 118: 1
• 5a Arnold FH. Angew. Chem. Int. Ed. 2019; 58: 14420
• 5b Hammer SC, Knight AM, Arnold FH. Curr. Opin. Green Sustainable Chem. 2017; 7: 23
• 6 Constable DJ. C, Jimenez-Gonzalez C, Henderson RK. Org. Process Res. Dev. 2007; 11: 133
• 7 Motley Fool Transcribers, BP (BP) Q2 2020 Earnings Call Transcript, see (accessed Feb 19, 2021): https://www.fool.com/earnings/call-transcripts/2020/08/06/bp-bp-q2-2020-earnings-call-transcript.aspx.
• 8a See (accessed Feb 19, 2021): https://hcss.nl/sites/default/ files/files/reports/HCSS_Scarcity_of_Minerals.pdf
• 8b See also (accessed Feb 19, 2021): https://www.pwc.com/ua/en/industry/metal_mining/assets/impact_of_minerals_metals_scarcity_on_business.pdf
• 9 See (accessed Nov 15, 2020): https://www.kitco.com/charts/ livepalladium.html
• 10a PTS: Lipshutz BH, Ghorai S, Leong WW. Y, Taft BR, Krogstad DV. J. Org. Chem. 2011; 76: 5061
• 10b TPGS-750-M: Lipshutz BH, Ghorai S, Abela AR, Moser R, Nishikata T, Duplais C, Krasovskiy A. J. Org. Chem. 2011; 76: 4379
• 11 Lipshutz BH, Aguinaldo GT, Ghorai S, Voigtritter K. Org. Lett. 2008; 10: 1325
• 12 Lipshutz BH, Taft BR. Org. Lett. 2008; 10: 1329
• 13 Lipshutz BH, Petersen TB, Abela AR. Org. Lett. 2008; 10: 1333
• 14 Dwars T, Paetzold E, Oehme G. Angew. Chem. Int. Ed. 2005; 44: 7174
• 15 Hayashi Y. Angew. Chem. Int. Ed. 2006; 45: 8103
• 16 Blackmond DG, Armstrong A, Coombe V, Wells A. Angew. Chem., Int. Ed. 2007; 46: 3798
• 17 Myers D. Surfactant Science and Technology, 3rd ed. 2006
• 18 Lipshutz BH. Curr. Opin. Green Sustainable Chem. 2018; 11: 1
• 19 Duplais C, Forman AJ, Baker BA, Lipshutz BH. Chem. Eur. J. 2010; 16: 3366
• 20a Breton GW, Shugart JH, Hughey CA, Conrad BP, Perala SM. Molecules 2001; 6: 655
• 20b Li C.-J. Tetrahedron 1996; 52: 5643
• 21a Krasovskiy A, Duplais C, Lipshutz BH. J. Am. Chem. Soc. 2009; 131: 15592
• 21b See also: Duplais C, Krasovskiy A, Lipshutz BH. Organometallics 2011; 30: 6090

See, as examples:
• 22a Lipshutz BH. Synthesis 1987; 325
• 22b Lipshutz BH. Synlett 1990; 119
• 22c Lipshutz BH. Synthetic Procedures Involving Organocopper Reagents, In Organometallics. A Manual; Schlosser, M., Ed.; Wiley: Chichester, 1994; 283
• 23 Huang S, Voigtritter KR, Under JB, Lipshutz BH. Synlett 2010; 2041
• 24a Mahoney WS, Brestensky DM, Stryker JM. J. Am. Chem. Soc. 1988; 110: 291
• 24b See also: Lipshutz BH. Synlett 2009; 509
• 25 Lipshutz BH, Huang S, Leong WW. Y, Zhong G, Isley NA. J. Am. Chem. Soc. 2012; 134: 19985
• 26a Lipshutz BH, Sengupta S. Org. React. 1992; 41: 138
• 26b It is appreciated that ‘RCu’ is more likely scribed as a halocuprate, R(X)CuZnX, but these halozinc (and not lithio- or magnesio-) cuprates are far from the electrophilic species needed to carry out the intended 1,4-additions.
• 27 Lipshutz BH, Ellsworth EL, Dimock SH. J. Am. Chem. Soc. 1990; 112: 5869
• 28 Lipshutz BH, Ghorai S, Cortes-Clerget M. Chem. Eur. J. 2018; 24: 6672
• 29 Zhao Q, Li C, Senanayake CH, Tang W. Chem. Eur. J. 2013; 19: 2261 ; and references therein
• 30 Handa S, Andersson MP, Gallou F, Reilly J, Lipshutz BH. Angew. Chem. Int. Ed. 2016; 55: 4914
• 31 See (accessed Feb 19, 2021): https://www.acsorg/content/acs/en/greenchemistry/research-innovation/endangered-elements.html.
• 32 Carole WA, Bradley J, Sarwar M, Colacot TJ. Org. Lett. 2015; 17: 5472
• 33 Martin R, Buchwald SL. Acc. Chem. Res. 2008; 41: 1461
• 34 Landstrom EB, Handa S, Aue DH, Gallou F, Lipshutz BH. Green Chem. 2018; 20: 3436
• 35 Handa S, Wang Y, Gallou F, Lipshutz BH. Science 2015; 349: 1087
• 36 Handa S, Jun B, Bora PP, Wang Y, Zhang X, Gallou F, Reilly J, Lipshutz BH. ACS Catal. 2019; 9: 2423
• 37 Pang H, Hu Y, Yu J, Gallou F, Lipshutz BH. J. Am. Chem. Soc. 2021; 143: 3373
• 38 Johansson SeechurnC. C. C, Kitching MO, Colacot TJ, Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
• 39 Forero-Cortes PA, Haydl AM. Org. Process Res. Dev. 2019; 23: 1478
• 40 Ruiz-Castillo P, Buchwald SL. Chem. Rev. 2016; 116: 12564
• 41 Zhang Y, Takale BS, Gallou F, Reilly J, Lipshutz BH. Chem. Sci. 2019; 10: 10556
• 42 Friis SD, Johansson MJ, Ackermann L. Nat. Chem. 2020; 12: 511
• 43 Zhao D, Xu P, Ritter T. Chem 2019; 5: 97
• 44 Uehling MR, King RP, Krska SW, Cernak T, Buchwald SL. Science 2019; 363: 405
• 45 Kutchukian PS, Dropinski JF, Dykstra KD, Li B, DiRocco DA, Strekfuss EC, Campeau L.-C, Cernak T, Vachal P, Davies IW, Krska SW, Dreher SD. Chem. Sci. 2016; 7: 2604
• 46 Thakore RR, Takale BS, Singhania V, Gallou F, Lipshutz BH. ChemCatChem 2021; 13: 212
• 47 Takale BS, Thakore RR, Casotti G, Li X, Gallou F, Lipshutz BH. Angew. Chem. Int. Ed. 2021; 60: 4158
• 48 See (accessed Feb 19, 2021): https://www.news.ucsb.edu/2020/ 019977/fighting-malaria-sustainably
• 49 Lipshutz BH. J. Org. Chem. 2017; 82: 2806
• 50 See (accessed Feb 19, 2021): https://www.coons.senate.gov/news/press-releases/senate-passes-sen-coons-bipartisan-bill-backed-by-delaware-companies-to-promote-sustainable-chemistry

For representative reports, see:
• 51a Lippincott DJ, Landstrom E, Cortes-Clerget M, Lipshutz BH, Buescher K, Schreiber R, Durano C, Parmentier M, Ye N, Wu B, Shi M, Yang H, Andersson M, Gallou F. Org. Process Res. Dev. 2020; 24: 841
• 51b Gallou F, Isley NA, Ganic A, Onken U, Parmentier M. Green Chem. 2016; 18: 14
• 52 Krell C, Schreiber R, Hueber L, Sciascera L, Zheng X, Clarke A, Haenggi R, Parmentier M, Rodde S, Baguia H, Keusch J, Gallou F. Org. Process. Res. Dev. submitted for publication
• 53 See (accessed Feb 19, 2021): https://www.epa.gov/greenchemistry/green-chemistry-challenge-winners

Reviews:
• 54a Lipshutz BH, Gallou F, Handa S. ACS Sustainable Chem. Eng. 2016; 4: 5838
• 54b Lipshutz BH, Ghorai S. Green Chem. 2014; 16: 3660

Reviews:
• 55a Steven A. Synthesis 2019; 51: 2632
• 55b La Sorella G, Strukul G, Scarso A. Green Chem. 2015; 17: 644
• 56 See (accessed Feb 19, 2021): https://www.acsgcipr.org/advancing-research
• 57a See (accessed Feb 19, 2021): https://communities.acs.org/ community/science/sustainability/green-chemistry-nexus-blog/blog/2020/03/26/the-recipient-of-the-2020-peter-j-dunn-award-for-green-chemistry-engineering-impact-in-the-pharmaceutical-industry
• 57b See also: Bailey J. D., Helbling E., Mankur A., Stirling M., Hicks F., Leahy D. K.; Green Chem.; 2021, 23: 788
• 58 See (accessed Feb 19, 2021): https://www.usatoday.com/ story/life/movies/2016/12/12/jerry-maguire-anniversary-tom-cruise-show-me-money/95300458
• 59 Hauer B. ACS Catal. 2020; 10: 8418

See, as examples:
• 60a An C, Shaw MH, Tharp A, Verma D, Li H, Wang H, Wang X. Org. Lett. 2020; 22: 8320
• 60b Wu B, Zhang S, Hong T, Zhou Y, Wang H, Shi M, Yang H, Tian X, Guo J, Bian J, Roache J, Delgado P, Mo R, Fridrich C, Gao F, Wang J. Org. Process Res. Dev. 2020; 24: 2780
• 61a Wang Y, Zhao H. Catalysts 2016; 6: 194
• 61b Huang X, Cao M, Zhao H. Curr. Opin. Chem. Biol. 2020; 55: 161

See, as examples:
• 62a Dander JE, Giroud M, Racine S, Darzi ER, Alvizo O, Entwistle D, Garg NK. Commun. Chem. 2019; 2: 82
• 62b Cosgrove SC, Thompson MP, Ahmed ST, Parmeggiani F, Turner NJ. Angew. Chem. Int. Ed. 2020; 59: 18156

For additional reviews on this topic appearing in 2020, see
• 63a Hastings CJ, Adams NP, Bushi J, Kolb SJ. Green Chem. 2020; 22: 6187
• 63b Doyon TJ, Narayan AR. H. Synlett 2020; 31: 230
• 63c Liu Y, Liu P, Gao S, Wang Z, Luan P, Gonzalez-Sabin J, Jiang Y. Chem. Eng. J. 2020; in press; DOI:
• 64 Hayashi Y. Chem. Sci. 2016; 7: 866
• 65 Hayashi Y. J. Org. Chem. 2021; 86: 1
• 66 Cortes-Clerget M, Akporji N, Zhou J, Gao F, Guo P, Parmentier M, Gallou F, Berthon J.-Y, Lipshutz BH. Nat. Commun. 2019; 10: 2169
• 67 Lipshutz B. H. and co-workers, manuscripts in preparation.
• 68 See: https://www.beyondbenign.org
• 69 Takale BS, Thakore RR, Gao ES, Gallou F, Lipshutz BH. Green Chem. 2020; 22: 6055
• 70 Takale BS, Thakore RR, Kong FY, Lipshutz BH. Green Chem. 2019; 21: 6258