Stepwise Operation of a Molecular Rotary Motor Driven by an Appel Reaction

Abstract

To date, only a small number of chemistries and chemical fueling strategies have been successfully used to operate artificial molecular motors. Here, we report the 360°directionally biased rotation of phenyl groups about a C−C bond, driven by a stepwise Appel reaction sequence. The motor molecule consists of a biaryl-embedded phosphine oxide and phenol, in which full rotation around the biaryl bond is blocked by the P−O oxygen atom on the rotor being too bulky to pass the oxygen atom on the stator. Treatment with SOCl 2 forms a cyclic oxyphosphonium salt (removing the oxygen atom of the phosphine oxide), temporarily linking the rotor with the stator. Conformational exchange via ring flipping then allows the rotor and stator to twist back and forth past the previous limit of rotation. Subsequently, the ring opening of the tethered intermediate with a chiral alcohol occurs preferentially through a nucleophilic attack on one face. Thus, the original phosphine oxide is reformed with net directional rotation about the biaryl bond over the course of the two-step reaction sequence. Each repetition of SOCl 2 −chiral alcohol additions generates another directionally biased rotation. Using the same reaction sequence on a derivative of the motor molecule that forms atropisomers rather than fully rotating 360°results in enantioenrichment, suggesting that, on average, the motor molecule rotates in the "wrong" direction once every three fueling cycles. The interconversion of phosphine oxides and cyclic oxyphosphonium groups to form temporary tethers that enable a rotational barrier to be overcome directionally adds to the strategies available for generating chemically fueled kinetic asymmetry in molecular systems.

Redox-powered autonomous unidirectional rotation about a C–C bond under enzymatic control

“…Covalent bonding interactions that lower energy barriers to bond rotation provide the basis for Bringmann's 'lactone' method and other more recent strategies for the enantioselective synthesis of atropisomers, 30,31 and related covalent bonding interactions are exploited in the rotary motor of Leigh and co-workers and other stepwise rotary molecular motors. 8,[32][33][34][35] Transient non-covalent bonding interactions, 36 as proposed for hydroxyaldehyde 2, have been used extensively in the asymmetric synthesis of atropisomers through dynamic kinetic resolution methods using organo-, transition metal and enzymatic catalysis. 31,37,38 In analogy to Turner's cyclic deracemization of a point chiral centre (Figure 1a), 29 deracemization of atropisomeric 1 occurs if the oxidation to hydroxyaldehyde 2 proceeds enantioselectively and is coupled to a non-selective reduction back to the diol 1.…”