Meanderings of a Curious Chemist

This article is dedicated with fond affection to my two mentors, the late Sir Derek H. R. Barton and William B. Motherwell, now Emeritus Professor at University College, London, and to Dr Béatrice Sire, my longstanding associate.

Abstract

This account relates briefly the personal trajectory of the author and the thought processes that went into solving synthetic problems and developing new reactions more generally useful in organic synthesis.

1 Preamble and Early Education

2 In France with Sir Derek Barton

3 Chemistry at Ecole Polytechnique and at the ICSN

4 Final Remarks

Key words

steroids - nitroalkenes - alkynes - radicals - allylations - vinylations - deoxygenation - betaines

Publication History

Received: 18 September 2022

Accepted after revision: 28 October 2022

Accepted Manuscript online:
28 October 2022

Article published online:
30 November 2022

• References

• 1 Even the storage of the food supply required constant vigilance. My mother recalls an occasion when she was horrified to wake up one morning to find the refrigerator black with swarming ants and other insects. The door of the refrigerator had not been locked properly the previous evening and all the critters had converged on it during the night and destroyed all its contents.
• 2 Another narrow escape took place on August 17, 1985, while visiting my parents with my wife and 22-month-old son Michael, at the height of the so-called civil war in Lebanon, when the only way into the Christian area north of Beirut where they lived was by boat via Cyprus. We drove to a nearby supermarket to buy some pasteurised milk and had barely returned home when a huge explosion rocked the house. A car bomb had exploded in front of the very same supermarket that killed more than 50 people, including the unfortunate cashier who took my money a few minutes earlier.
• 3 One of the less dangerous accomplishments with my friend Toni was the presentation of an hour of chemistry magic for local school children gathered one Saturday afternoon at a special one-day sporting event. Most of those kids are now grandparents but still remember the presentation, very probably the first of its kind in Lebanon at the time, which took place nearly 50 years ago. They remind me of it when I occasionally bump into one of them on my visits to my—fortunately still alive—mother. Incidentally, my friend Toni is not a chemist but a superbly gifted civil engineer.
• 4 Professors Makluf Haddadin, who sadly passed away just after this manuscript was submitted, and the late Costas Issidorides were exceptional organic chemistry teachers. Together, they discovered the Beirut reaction (see: Haddadin, M. J.; Issidorides, C. H.; Application of Benzofurazan Oxide to the Synthesis of Heteroaromatic N-Oxides. Heterocycles 1976, 4, 767), which brought fame and money to the Chemistry Department. Both remained to teach and help the students throughout the war in Lebanon, despite the violence and often extreme danger. This is a humbling example of extraordinary courage and devotion to the university and its students.
• 5a Zard SZ. Basking in the Shadow of a Great Chemist: Happy Times with Sir Derek Barton. In The Bartonian Legacy. Potier P, Scott AI. Imperial College Press; London: 2001. https://www.google.com/books/edition/The_Bartonian_Legacy/f_K3CgAAQBAJ?hl=en (accessed Nov. 22, 2022)
• 5b This book is not wildly available, but the author would be happy to supply a PDF file of this chapter upon request.
• 6 Zard SZ. Synlett 2009; 333
• 7 Zard SZ. Helv. Chim. Acta 2012; 95: 1730
• 8 Hassner A, Namboothiri I. Organic Syntheses Based on Name Reactions: A Practical Guide to Over 700 Transformations. Elsevier; Amsterdam: 2011
• 9 Barton DH. R, Parekh SI. Half a Century of Radical Chemistry . Cambridge University Press; Cambridge: 1993
• 10 Pines SH. Org. Proc. Res. Dev. 2004; 8: 708
• 11 van Rheenen V. Tetrahedron Lett. 1969; 10: 985
• 12 Zard SZ. Angew. Chem. Int. Ed. 2006; 45: 2496
• 13 Boivin J, Elkaim L, Zard SZ. Tetrahedron Lett. 1992; 33: 1285
• 14a Trimble LA, Street IP, Perrier H, Trembley NM, Weech PK, Bernstein MA. Biochemistry 1993; 32: 12560
• 14b Reeves JT, Fandrick DR, Tan Z, Song JJ, Rodriguez S, Qu B, Kim S, Niemeier O, Li Z, Byrne D, Campbell S, Chitroda A, DeCroos P, Fachinger T, Fuchs V, Gonnella NC, Grinberg N, Haddad N, Jäger B, Lee H, Lorenz JC, Ma S, Narayanan BA, Nummy LJ, Premasiri A, Roschangar F, Sarvestani M, Shen S, Spinelli E, Sun X, Varsolona RJ, Yee N, Brenner M, Senanayake CH. J. Org. Chem. 2013; 78: 3616
• 15a Abidi SL. J. Chem. Soc., Chem. Commun. 1985; 1222
• 15b Abidi SL. Tetrahedron Lett. 1986; 27: 267
• 15c Abidi SL. J. Org. Chem. 1986; 51: 2687
• 16 Corey EJ, Seibel WL, Kappos JC. Tetrahedron Lett. 1987; 28: 4921
• 17 Zard SZ. Chem. Commun. 2002; 1555
• 18 Ridley D. Aust. J. Chem. 2015; 68: 538
• 19a Zard SZ. Synlett 1996; 1148
• 19b Zard SZ. Chem. Soc. Rev. 2008; 37: 1603
• 20a Boivin J, Yousfi M, Zard SZ. Tetrahedron Lett. 1994; 35: 5629
• 20b Quiclet-Sire B, Saunier J.-B, Zard SZ. Tetrahedron Lett. 1996; 37: 1397
• 20c Cassayre J, Quiclet-Sire B, Saunier J.-B, Zard SZ. Tetrahedron 1998; 54: 1029
• 20d Cassayre J, Quiclet-Sire B, Saunier J.-B, Zard SZ. Tetrahedron Lett. 1998; 39: 8995
• 21a Zard SZ. Aust. J. Chem. 2006; 59: 663
• 21b Zard SZ. Macromolecules 2020; 53: 8144
• 22 Zard SZ. Helv. Chim. Acta 2019; 102: e1900134
• 23a Quiclet-Sire B, Zard SZ. J. Am. Chem. Soc. 2015; 137: 6762
• 23b Huang Q, Michalland J, Zard SZ. Angew. Chem. Int. Ed. 2019; 58: 16936
• 24a Matyjaszewski K. Macromolecules 2020; 53: 495
• 24b Perrier S. Macromolecules 2017; 50: 7433
• 25 Quiclet-Sire B, Zard SZ. Isr. J. Chem. 2017; 57: 202
• 26a Quiclet-Sire B, Zard SZ. Heterocycles 2022; 105: 309
• 26b Zard SZ. Chem. Eur. J. 2020; 26: 12689
• 26c El Qacemi M, Petit L, Quiclet-Sire B, Zard SZ. Org. Biomol. Chem. 2012; 10: 5707
• 27a Quiclet-Sire B, Zard SZ. Tetrahedron Lett. 1998; 39: 9435
• 27b Liard A, Quiclet-Sire B, Zard SZ. Tetrahedron Lett. 1996; 37: 5877
• 28 Siddiqui MA, Driscoll JS, Abushanab E, Kelley JA, Barchi JJ. Jr, Marquez VE. Nucleosides, Nucleotides Nucleic Acids 2000; 19: 1
• 29 Zard SZ. Acc. Chem. Res. 2018; 51: 1722
• 30a Quiclet-Sire B, Zard SZ. J. Am. Chem. Soc. 1996; 118: 9190
• 30b Boivin J, Quiclet-Sire B, Ramos L, Zard SZ. Chem. Commun. 1997; 353
• 31a Bertrand F, Leguyader F, Liguori L, Ouvry G, Quiclet-Sire B, Seguin S, Zard SZ. C. R. Acad. Sci. Paris 2001; II4: 547
• 31b Li Z, Zard SZ. Org. Lett. 2009; 11: 2868
• 31c Charrier N, Zard SZ. Angew. Chem. Int. Ed. 2008; 47: 9443
• 32a Debien L, Quiclet-Sire B, Zard SZ. Acc. Chem. Res. 2015; 48: 1237
• 32b Michalland J, Zard SZ. Org. Lett. 2021; 23: 8018
• 33 Zard SZ. Synthesis 2019; 51: 1006
• 34 When I was first invited as a speaker in 2001, I had not anticipated the time available to mingle with colleagues: at meals, at coffee breaks, at the poster sessions, and of course on the lovely hiking trails. What is more exhilarating for a young(ish) participant than to find himself sitting next to his chemistry hero at breakfast in front of a breath-taking view of Lake Lucerne and the lush mountains surrounding it? This happened to me one morning when Prof. E. J. Corey came and sat next to me for breakfast. We both had arrived early and this gave us plenty of time to chat. This encounter was the first of several more and culminated in an invitation for my wife and I to lunch at his home on one of our trips to the USA. It turns out that Prof. Corey very much enjoys cooking and actually cooked a delicious lunch for us. We thus had a chance to meet his charming wife Claire and, after the meal, to taste honey that came from a beehive kept by Professor Andy Myers, certainly the highest qualified beekeeper in the world! As President in 2007, I felt greatly honoured when the late Prof. Rolf Huisgen accepted my invitation to be my guest of honour. The first time I came across Prof. Huisgen was in my last undergraduate year, when I took the train to Liverpool in the spring of 1978 to attend a one-day symposium of the RSC. I wanted to listen to Tony Barrett, then a very young lecturer at Imperial College, who had taken me under his wing. Prof. Huisgen was also a speaker, and his lecture was indeed one to behold and to remember. It was extremely clear, perfectly timed, and he had kept three or four slides in reserve with which he utterly demolished the very first question from the audience, which, unwisely, was asked with a hint of aggressiveness. There were no more questions after that. Our young jaws dropped in awe and admiration. At the Bürgenstock Conference, Prof. Huisgen asked probing questions at all the lectures and, as if this was not sufficient, asked me to bring my computer one afternoon and explain to him the chemistry we were doing over a cup of tea. I was flattered but a little apprehensive at perhaps not being able to completely satisfy his tremendous intellectual curiosity. Two years later, I was invited to speak at LMU as part of a week-long lecture tour in Germany. The lecture at LMU was on a Monday, and I planned to take the train to Munich on Sunday morning so as to have time to settle and rest. When Prof. Huisgen found out, he insisted on picking me up on the Sunday afternoon and taking me to one of the three Pinakotheken not very far from the hotel. The February snow and sleet did not seem to bother him at all (he was 89 years old at the time!) and, once in the Pinakotheke, I had another jaw-dropping experience. He knew essentially everything about all the paintings; he knew in which room they were located and even knew the museum wardens. All the while, I was nervously trying not to say something stupid and make a fool of myself, an almost impossible task. When I returned to France, I was pleasantly surprised to receive a very nice original photo of a flower he had taken, with an exceedingly kind, beautifully handwritten note on the back. It is one of my most highly prized possessions. Prof. Huisgen was an accomplished artist as well as one of the greatest organic chemists.