Electric-Field Catalysis on Carbon Nanotubes in Electromicrofluidic Reactors: Monoterpene Cyclizations

Abstract

The control over the movement of electrons during chemical reactions with oriented external electric fields (OEEFs) has been predicted to offer a general approach to catalysis. Recently, we suggested that many problems to realize electric-field catalysis in practice under scalable bulk conditions could possibly be solved on multiwalled carbon nanotubes in electromicrofluidic reactors. Here, we selected monoterpene cyclizations to assess the scope of our system in organic synthesis. We report that electric-field catalysis can function by stabilizing both anionic and cationic transition states, depending on the orientation of the applied field. Moreover, electric-field catalysis can promote reactions which are barely accessible by general Brønsted and Lewis acids and field-free anion-π and cation-π interactions, and drive chemoselectivity toward intrinsically disfavored products without the need for pyrene interfacers attached to the substrate to prolong binding to the carbon nanotubes. Finally, interfacing with chiral organocatalysts is explored and evidence against contributions from redox chemistry is provided.

Keywords: Oriented external electric fields; anion-π catalysis; carbon nanotubes; cation-π catalysis; cyclizations; flow chemistry; hydride shifts; microfluidics; terpenes.

Figure 1

The electromicrofluidic system devised for electric‐field catalysis of terpene cyclization, with substrate 1 and notional transition states of the first step, a C−Cl bond cleavage. A 250 μm thin foil with the flow channel is sandwiched between MWCNT‐coated graphite and Pt electrodes. The graphite electrode used as anode (blue) or cathode (red) produces OEEFs of opposite direction (colored tagged arrows pointing from positive to negative). To activate terpene cyclization, these OEEFs should i) directly catalyze C−Cl bond cleavage (curved arrows, movement of electrons) and ii) polarize MWCNTs with induced macrodipoles (IM, black tagged arrows, positive to negative) to induce anion‐/cation‐π interactions for catalysis of the same C−Cl bond cleavage.

Figure 2

Cyclization of 1 (100 mM) in toluene catalyzed by negative (b/c, e/f) and positive (c/d, g/h) electric fields, with cyclization mechanisms (a, i, j) and color‐coded products 2–6. (c, e, g) Substrate (S), identified products (P) and unidentified others (O) after passing once through the electromicrofluidic reactor as a function of the applied current (c, v=15 μL min⁻¹) and the flow rate (e, g, I=±5.0 A). Symbols inside doughnut charts indicate orientation (red, MWCNT‐coated graphite as cathode, referred to as negative electric fields; blue, MWCNTs as anode, positive electric fields) and strength (light/dark color) of the applied field, and flow velocity (fast=thick solid, slow=thin dashed curly lines; peripheral circular arcs distinguish mechanisms with deprotonation and with (red) and without (green) hydride shift; *including small amounts of p‐cymene 7 (7 %, Figure S32). (i, j) Speculative transition states TS‐3 to TS‐8 stabilized by negative (i, red tagged arrows) and positive electric fields (j, blue tagged arrows). Electron translocation during reactions is indicated by curved arrows, opposite color and directions indicate activation, identical color and orientation inactivation by electric fields. TS‐4 and TS‐7 speculate on chemoselectivity, emphasizing how alignment of the carbocation‐chloride ion pairs to increasing electric fields could activate the hydride shifts to reach 5 and 6 (curved arrows, color opposite to field) and hinder chloride addition to 2 (dashed curved arrows, same light color) and proton elimination to 3 and 4 (dashed curved arrows, same dark color).

Figure 3

Interfacing of the Jacobsen catalyst 8 (gold, a–e, 100 mol %; f, g, 30 mol %) with negative (b, c) and positive electric‐field catalysis (d–g) to cyclize 100 mM 1 in toluene. (a) Product distribution for partial (30 min) and full conversion of 1 (22 h) in electromicrofluidics‐free solution. (b, d, f) Substrate (S), product (P) and others (O) after one passage through the electromicrofluidic reactor as a function of the applied current (v=10 μL min⁻¹), and (c, e, g) doughnut charts for product distributions, encoded as in Figure 2.

Figure 4

Assessment of electron transfer under experimental conditions. a) Absorption spectra of hydroquinone 9 (black) and equimolar 10 (brown, oversaturated at A≫1.5). b) Absorption spectra of reaction mixture after passing once through the electromicrofluidic reactor at increasing current up to I=±5.0 A (blue, apparent voltage V=1.36 V).