The Dynamic Nature of Phosphorus

POTENTIAL ENERGY

The Dynamic Nature of Phosphorus Liu (Leo) Liu1,*

This research area stimulated my desire to expand my scientific knowledge during my time in the Zhao group at Xiamen University as I investigated the chemical behavior of these high-valent phosphorus compounds. At the beginning of my third year in my PhD, I had the fantastic opportunity to work with Prof. Guy Bertrand at the University of California, San Diego (UCSD) as a joint graduate student. There I was inspired to explore main-group chemistry targeting air-sensitive lowvalent phosphorus compounds. I was very excited to touch this new area, although initially I had some difficulty with handling such highly reactive molecules.

Dr. Liu (Leo) Liu is a post-doctoral fellow in Prof. Douglas W. Stephan’s group at the University of Toronto. Before this, he received his BS degree in chemistry (2011) and PhD degree in organic chemistry (2016) under the supervision of Prof. Yufen Zhao at Xiamen University. He was awarded the 2014 National Scholarship for outstanding PhD students from the Chinese Ministry of Education. He spent 2 years as a joint graduate student studying main-group chemistry in Prof. Guy Bertrand’s laboratory at the University of California, San Diego (2013–2015). He has published over 35 peer-reviewed papers, and his research spans synthetic and computational chemistry.

For several decades, carbenes defying the well-known octet role were thought to be only laboratory curiosities as transient intermediates. This paradigm changed in 1988 with the isolation of the first singlet carbene stable at ambient temperature, pioneered by Bertand and colleagues.2 Via the introduction of the right substituents around the carbene center, numerous singlet carbenes have been readily accessible and shown to exhibit a variety of applications relevant to synthetic chemistry, materials, and the biological sciences. I became captivated by these ambiphilic species during my time at UCSD, and by combining this with my prior phosphorus expertise, I specifically targeted the phosphorus analogs of carbenes, i.e., stable free phosphinidenes, one of the world’s toughest challenges.

What initially drew me to phosphorus chemistry was a short conversation in which Prof. Yufen Zhao introduced a class of magical molecules: N-phosphoryl amino acids (Figure 1A). The remarkable reactions of N-phosphoryl amino acids with nucleoside mixtures lead to the simultaneous formation of peptides and oligonucleotides, two classes of molecules essential for life.1

In the inaugural issue of Chem, we reported the synthesis of the first stable singlet phosphinidene, namely a (phosphino)phosphinidene (Figure 1B).3 This was achieved via the elimination of carbon monoxide from the corresponding (phosphanyl)phosphaketene under UV irradiation. Of particular importance, this phosphinidene can be stored in the

solid state at room temperature under inert atmosphere for weeks without noticeable decomposition. Preliminary studies demonstrated that, similar to singlet carbenes, the (phosphino)phosphinidene features a PP multiple bond and undergoes a [2 + 1] cycloaddition with an electron-poor alkene and a [1 + 1] coupling reaction with isocyanides. In contrast to singlet carbenes, sterically unprotected (phosphino)phosphinidenes spontaneously dimerize to afford the ensuing diphosphenes. We believe that much can be drawn from the comparison of carbene and phosphinidene chemistry. The first stable carbene was discovered just shy of three decades ago, and its chemistry has flourished tremendously in such a short span. Although stable phosphinidenes are in their infancy, given the achievements that resulted from the isolation of carbenes, they could certainly follow in the footsteps of carbenes and be employed in a wide range of applications in the near future. Gaining this solid background in maingroup chemistry, I next joined the group of Prof. Douglas W. Stephan at the University of Toronto as a post-doctoral fellow in the fall of 2016 to work on frustrated Lewis pair (FLP) chemistry. This research area has achieved tremendous success since Stephan’s seminal 2006 discovery of the transition-metal-free reversible hydrogen activation by p-(Mes2P) C6F4(B(C6F5)2) (Mes = mesityl).4 Generally, a FLP system has a nucleophilic center and an electrophilic center as independent active sites. It is commonly accepted that FLP systems form a loosely associated transient ‘‘encounter complex’’ (Figure 1C) that provides a pocket with an electric field, in which substrates are efficiently polarized and readily activated by a two-electron push-pull

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A

B

O R1O R1O

P

O Ar

R

Ar

O

N OH

N H

N P

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Ar

N-phosphoryl amino acid

P

N

O

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O O

nucleoside

amino acid

Ar

Ar C N

N polypeptide

P

oligonucleotide

R

N P

P

C

N R

Ar

Ar

P(V)

P

N

N

P(I)

P (III)

C

D

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P

P

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X

E

E

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frustrated Lewis pair

P

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E

frustrated Lewis pair

X2

SET

heterolysis

homolysis

X2

X

P

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P

"encounter complex"

X

E

frustrated radical pair

Mes3P

+

E(C6F5)3

SET

Mes3P

+

E(C6F5)3

Figure 1. Schematic Overview Outlining Our Studies (A) Remarkable reactivity of N-phosphoryl amino acids. (B) Reactivity of (phosphino)phosphinidene toward maleic anhydride and isocyanides. (C) A two-electron diamagnetic reaction mechanism for FLP reactivity. (D) A one-electron paramagnetic reaction mechanism for FLP reactivity.

interaction. This process results in the heterolytic cleavage of chemical bonds. In this issue of Chem, we describe a one-electron paramagnetic reaction mechanism for FLP reactivity (Figure 1D).5 This mechanism is initiated with single-electron transfer (SET) from

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a Lewis base to a Lewis acid to form a transient frustrated radical pair (FRP). Notably, compared with FLPs, the resulting FRP features two extraordinarily reactive ion radical centers coupled with a stronger electric field and is thus capable of activating substrates in the homolytic fashion.

We report the SET equilibrium between the FLP consisting of Mes3P/ E(C6F5)3 (E = B, Al) and the transient FRP of [Mes3P$]+/[$E(C6F5)3] (Figure 1D). In remarkable contrast to the observations of tBu3P/E(C6F5)3, the reactions of Mes3P/E(C6F5)3 toward tetrachloro-1,4-benzoquinone or

Ph3SnH underwent intermediates.

radical

salt

Over a decade after the pioneering work of FLP chemistry, our results demonstrate an alternative reaction mechanism for FLP reactivity. We believe this finding broadens our understanding of FLP systems and opens a new chapter in FLP chemistry.

me, which has made me the chemist I am today, as well as the students and researchers I interacted with in the various labs. In my opinion, the most important factor in being successful is pursuing what you are interested in. When I get the opportunity to establish my own lab, I plan to provide an atmosphere where my students can freely pursue their research interests.

2. Igau, A., Gru¨tzmacher, H., Baceiredo, A., and Bertrand, G. (1988). J. Am. Chem. Soc. 110, 6463–6466. 3. Liu, L., Ruiz, D.A., Munz, D., and Bertrand, G. (2016). Chem 1, 147–153. 4. Welch, G.C., San Juan, R.R., Masuda, J.D., and Stephan, D.W. (2006). Science 314, 1124– 1126. 5. Liu, L., Cao, L.L., Shao, Y., Me´nard, G., and Stephan, D.W. (2017). Chem 3, this issue, 259–267. 1Department

Finally, I want to express my deepest appreciation for the time Profs. Zhao, Bertrand, and Stephan dedicated to

of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada

1. Ni, F., Fu, C., Gao, X., Liu, Y., Xu, P., Liu, L., Lv, Y., Fu, S., Sun, Y., Han, D., et al. (2015). Sci. China Chem. 58, 374–382.

*Correspondence: [email protected] http://dx.doi.org/10.1016/j.chempr.2017.07.002

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