Stephen P. Fletcher

Conversion of light into macroscopic helical motion

A key goal of nanotechnology is the development of artificial machines capable of converting molecular movement into macroscopic work. Although conversion of light into shape changes has been reported and compared to artificial muscles, real applications require work against an external load. Here, we describe the design, synthesis and operation of spring-like materials capable of converting light energy into mechanical work at the macroscopic scale. These versatile materials consist of molecular switches embedded in liquid-crystalline polymer springs. In these springs, molecular movement is converted and amplified into controlled and reversible twisting motions. The springs display complex motion, which includes winding, unwinding and helix inversion, as dictated by their initial shape. Importantly, they can produce work by moving a macroscopic object and mimicking mechanical movements, such as those used by plant tendrils to help the plant access sunlight. These functional materials have potential applications in micromechanical systems, soft robotics and artificial muscles.

Current Methods for Asymmetric Halogenation of Olefins

This Minireview discusses the progress made in developing reactions where an olefin is subjected to an asymmetric halogenation. It aims to serve as a reference for the studies reported to date, including preliminary work and mechanistic studies. The current state of the art, scope, and limitations of these processes are discussed.

Formation of Quaternary Centers by Copper‐Catalyzed Asymmetric Conjugate Addition of Alkylzirconium Reagents

Pure and simple: Alkylzirconocenes generated in situ from simple alkenes are used in highly enantioselective copper-catalyzed 1,4-addition reactions to trisubstituted cyclic enones to generate quaternary centers. These reactions operate at room temperature under a range of conditions and tolerate many functional groups. Cp=cyclopentadienyl, Tf=trifluoromethanesulfonyl. Copyright

Catalytic asymmetric carbon–carbon bond formation using alkenes as alkylmetal equivalents

Catalytic asymmetric conjugate addition reactions with organometallic reagents are powerful reactions in synthetic chemistry. Procedures that use non-stabilized carbanions have been developed extensively, but these suffer from a number of limitations that prevent their use in many situations. Here, we report that alkylmetal species generated in situ from alkenes can be used in highly enantioselective 1,4-addition initiated by a copper catalyst. Using alkenes as starting materials is desirable because they are readily available and have favourable properties when compared to pre-made organometallics. High levels of enantioselectivity are observed at room temperature in a range of solvents, and the reaction tolerates functional groups that are not compatible with comparable methods—a necessary prerequisite for efficient and protecting-group-free strategies for synthesis. Organometallic reagents are widely used as nucleophiles in asymmetric catalysis. Here, alkylmetal species generated in situ by hydrometallation of alkenes are used in enantioselective copper-catalysed C–C bond formation. The process is formally an asymmetric reductive coupling of an alkene to an enone, and tolerates many functional groups.

Transmission of chirality through space and across length scales

Chirality is a fundamental property and vital to chemistry, biology, physics and materials science. The ability to use asymmetry to operate molecular-level machines or macroscopically functional devices, or to give novel properties to materials, may address key challenges at the heart of the physical sciences. However, how chirality at one length scale can be translated to asymmetry at a different scale is largely not well understood. In this Review, we discuss systems where chiral information is translated across length scales and through space. A variety of synthetic systems involve the transmission of chiral information between the molecular-, meso- and macroscales. We show how fundamental stereochemical principles may be used to design and understand nanoscale chiral phenomena and highlight important recent advances relevant to nanotechnology. The survey reveals that while the study of stereochemistry on the nanoscale is a rich and dynamic area, our understanding of how to control and harness it and dial-up specific properties is still in its infancy. The long-term goal of controlling nanoscale chirality promises to be an exciting journey, revealing insight into biological mechanisms and providing new technologies based on dynamic physical properties.

Backbone Modification of Retinal Induces Protein-like Excited State Dynamics in Solution

The drastically different reactivity of the retinal chromophore in solution compared to the protein environment is poorly understood. Here, we show that the addition of a methyl group to the C═C backbone of all-trans retinal protonated Schiff base accelerates the electronic decay in solution making it comparable to the proton pump bacteriorhodopsin. Contrary to the notion that reaction speed and efficiency are linked, we observe a concomitant 50% reduction in the isomerization yield. Our results demonstrate that minimal synthetic engineering of potential energy surfaces based on theoretical predictions can induce drastic changes in electronic dynamics toward those observed in an evolution-optimized protein pocket.

Asymmetric Conjugate Additions and Allylic Alkylations Using Nucleophiles Generated by Hydro‐ or Carbometallation

This Minireview discusses catalytic asymmetric conjugate addition and allylic alkylation reactions where the nucleophiles were generated in situ by hydrometallation or carbometallation. This exciting recent trend in asymmetric catalysis promises to expand the range of transformations available for the rapid and selective assembly of complex, functional molecules for both academic and industrial research. This Minireview aims to serve as a reference for studies reported to date and discusses the current state-of-the-art, scope and limitations of these processes.

Enantioselective Copper(I)-Phosphoramidite Catalyzed Addition of Alkylzirconium Species to Acyclic Enones

Catalytic asymmetric conjugate addition reactions of alkylzirconium species to acyclic enones are reported. The alkylzirconium nucleophiles are generated in situ by hydrozirconation of alkenes with the Schwartz reagent. The reaction proceeds under mild and convenient conditions. A variety of functionalized nucleophiles can be used, and the method tolerates some variation in enone scope. The method uses a new chiral nonracemic phosphoramidite ligand in a complex with copper triflate.

Copper-catalyzed asymmetric conjugate addition of alkylzirconium reagents to cyclic enones to form quaternary centers

This protocol describes the catalytic asymmetric formation of all-carbon quaternary centers—a distinctive feature of many natural products and pharmaceuticals—via conjugate addition of alkylzirconium reagents to a tertiary enone. This methodology uses alkenes as starting materials and enables the incorporation of functional groups. The alkylzirconium reagent is generated in situ by mixing the alkene with the Schwartz reagent. The alkylzirconium is added to a solution containing a copper-ligand complex, and then the enone is added to the mixture. The addition of pent-4-en-1-ylbenzene to 3-methyl-2-cyclohexenone is detailed herein as a generic example. This procedure works at room temperature (∼25 °C), and it is scalable to at least 1.5 g. The setup of the reaction takes 3–5 h and the reaction goes to completion within 4–20 h.

Synthetic control of retinal photochemistry and photophysics in solution.

Understanding how molecular structure and environment control energy flow in molecules is a requirement for the efficient design of tailor-made photochemistry. Here, we investigate the tunability of the photochemical and photophysical properties of the retinal-protonated Schiff base chromophore in solution. Replacing the n-butylamine Schiff base normally chosen to mimic the saturated linkage found in nature by aromatic amines results in the reproduction of the opsin shift and complete suppression of all isomerization channels. Modification of retinal by directed addition or removal of backbone substituents tunes the overall photoisomerization yield from 0 to 0.55 and the excited state lifetime from 0.4 to 7 ps and activates previously inaccessible reaction channels to form 7-cis and 13-cis products. We observed a clear correlation between the presence of polarizable backbone substituents and photochemical reactivity. Structural changes that increase reaction speed were found to decrease quantum yields, and vice versa, so that excited state lifetime and efficiency are inversely correlated in contrast to the trends observed when comparing retinal photochemistry in protein and solution environments. Our results suggest a simple model where backbone modifications and Schiff base substituents control barrier heights on the excited-state potential energy surface and therefore determine speed, product distribution, and overall yield of the photochemical process.