Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen.

Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp2-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C-H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C-H arylation/Cu(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls.

An autonomous chemically fuelled small-molecule motor.

Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.

A three-compartment chemically-driven molecular information ratchet.

We describe a three-compartment rotaxane information ratchet in which the macrocycle can be directionally transported in either direction along an achiral (disregarding isotopic labeling) track. Chiral DMAP-based catalysts promote a benzoylation reaction that ratchets the displacement of the macrocycle, transporting it predominantly to a particular end compartment determined by the handedness of the catalyst.

Efficient access to orthoquinols and their [4 + 2] cyclodimers via SIBX-mediated hydroxylative phenol dearomatization.

SIBX, the nonexplosive formulation of the lambda5-iodane 2-iodoxybenzioc acid (IBX), safely and efficiently mediates the hydroxylative dearomatization of various 2-alkylphenols and napthols into orthoquinols or their [4 + 2] cyclodimers. Reactions are typically run at room temperature using SIBX as a suspension in THF. Using these conditions, natural products such as the cyclodimer of the terpene carvacrol and, for the first time, the shikimate-derived (+/-)-grandifloracin were prepared in one step from their respective phenolic precursor.

Studies on the total synthesis of lactonamycin: synthesis of the CDEF ring system.

A concise and efficient synthesis of the tetracyclic CDEF ring system of lactonamycin (1) is described. The key step involved the Lewis acid mediated, intramolecular Friedel-Crafts acylation of carboxylic acid 6 to produce the tetracyclic CDEF core structure of target 1. The synthesis of 6 was carried out using a high-yielding Negishi coupling of benzyl bromide 7 with triflate 8, which was accessible in 11 steps and 31% overall yield on a multigram scale starting from trihydroxy acid 9.