Araceli G. Campaña

Light-driven transport of a molecular walker in either direction along a molecular track.

Nature uses bipedal motor proteins that “walk” down intracellular tracks to perform essential tasks in a variety of key biological processes. Although the molecular mechanisms through which these fascinating linear motors operate are beginning to be understood, there are still few synthetic mimics that exhibit the most important characteristics of natural motors, namely repetitive, progressive, processive, and directional walker transport along a molecular track. Several walker–track systems based on DNA have been described, and recently our research group reported a smallmolecule system, in which the migration of a walker unit along a four-foothold track could be biased in one direction through an information ratchet type of Brownian ratchet mechanism. 6] Herein we report the design, synthesis, and operation of a small-molecule walker–track conjugate, in which the walker can be transported in either direction along a four-foothold molecular track (roughly 1.5 times more likely to take a step in one direction than the other), depending on the sequence of four applied stimuli: acid or base for mutually exclusive “foot” dissociation and UV light or visible light (plus iodine) to induce or release ring strain between the walker and the track. The design (Figure 1) is closely related to the previously reported small-molecule walker–track system, which features a walker with one hydrazone foot (labile in acid; locked in base) and one disulfide foot (labile in base; locked in acid). The crucial difference is that a stilbene unit has been added between the internal aldehyde and the disulfide footholds of the track (Scheme 1). The key to achieving directionality lies in the isomerization of the stilbene moiety, through which significant ring strain can be induced in the positional (constitutional) isomer in which the walker unit bridges the stilbene linkage (Figure 1 and Scheme 2b). E!Z isomerization provides a driving force

Understanding the Exceptional Hydrogen-Atom Donor Characteristics of Water in TiIII-Mediated Free-Radical Chemistry

In recent years solid evidence of HAT reactions involving water as hydrogen atom source have been presented. In this work we demonstrate that the efficiency of titanocene(III) aqua complexes as an unique class of HAT reagents is based on two key features: (a) excellent binding capabilities of water toward titanocene(III) complexes and (b) a low activation energy for the HAT step. The theory has predictive capabilities fitting well with the experimental results and may aid to find more examples of this remarkable radical reaction.

Divergent Titanium‐Mediated Allylations with Modulation by Nickel or Palladium

Titanocene(III)-mediated radical processes are important tools for the formation of C C bonds under mild conditions, and are compatible with many functional groups. Moreover, titanium(III) complexes can be used substoichiometrically, which has allowed the development of enantioselective versions of these reactions. A serious limitation of these radical processes, however, derives from the fact that titanium(III)-mediated radical generation requires reactive substrates, such as allylic halides, which are often cumbersome in introduction and manipulation. Allylic carbonates and carboxylates, in contrast, are easily prepared and handled but are inert against titanocene(III) complexes. Nevertheless, it is known that nickel and palladium complexes can readily activate allylic carbonates and carboxylates I (Scheme 1) to form h-allylmetal complexes (II). On the basis of these results, we deemed that the combination of palladium or nickel derivatives with titanocene(III) complexes would facilitate the development of novel allylation processes using accessible allyl carbonates or carboxylates. In the case of palladium catalysis, it is known that the Oppolzer-type cyclization of organometallic species (II, M = Pd, Scheme 1) to cyclic derivatives (VI) is relatively slow at room temperature. Thus, reduction of II by a singleelectron-transfer reagent, such as [Cp2TiCl], [6] could lead to the allylic radical III, which might be eventually trapped by a second [Cp2TiCl] species to give an allylic titanium(IV) complex IV. Finally, nucleophilic attack of the organometallic derivative IV on an aldehyde or other electrophilic reagent would provide the corresponding allylation product V. On the other hand, nickel-catalyzed carbocyclizations, via intermediates such as II (M = Ni, Scheme 1) to cyclic derivatives VI, are relatively fast at room temperature. Once formed, VI might be reduced by [Cp2TiCl] to a primary radical VII, which could be trapped by a second [Cp2TiCl] species to give an alkyl titanium(IV) complex VIII. Hydrolysis of the organometallic derivative VIII would yield carbocycles IX. Thus, we anticipated that the use of palladium or nickel catalysts could modulate titanium(III) to drive allylation reactions with allyl carboxylates by two different pathways, either through intermolecular coupling with electrophilic reagents or to give carbocyclic derivatives by an intramolecular allylation. To check our hypothesis, we chose allylic carbonate E-1 as a model allylation reagent. Thus, reaction of decanal with carbonate E-1 and an excess of [Cp2TiCl] (2.0 equiv), [8] in the presence of PdCl2 (20 mol%) and triphenylphosphine, [9] gave the expected coupling product 2 as a single stereoisomer in 76% yield (Scheme 2). In contrast, when carbonate E-1 was treated with an excess of [Cp2TiCl] (2.0 equiv) in the presence of [NiCl2(PPh3)2] (20 mol%), a mixture of carbocycles 3 and 4 (4:1 ratio) was obtained in almost quantitative Scheme 1. Mechanism for palladium-catalyzed, titanocene-mediated allylation of carbonyl compounds and nickel-catalyzed, titanocenemediated carbocylization of allylic carboxylates. [M] = transition metal catalyst; Cp = cyclopentadienyl; E = electrophilic reagent (e.g. aldehyde).R = OEt, Me, or Ph.

Unexpected TiIII/Mn-Promoted Pinacol Coupling of Ketones

Titanocene(III) chemistry has emerged in the last decades as an indispensable tool in C-C bond-forming reactions. In this context, pinacol and related reactions allow the stereoselective synthesis of vicinal diols. In this work, we present new applications of these reactions using as starting materials aromatic ketones. Simple and smooth reaction conditions have been developed and have been applied for inter- and intramolecular processes. We also describe that although Cp(2)TiCl is usually used as a monoelectronic reducing agent, it can be also used as an efficient Lewis acid.

Recent applications of Cp2TiCl in natural product synthesis

This review highlights the recent applications of titanocene(III) complexes in the field of natural product synthesis from the seminal precedents to the development of modern catalytic methods. The power of the titanocene(III)-based approaches is demonstrated by the straightforward syntheses of many natural products from readily available starting materials.

Water control over the chemoselectivity of a Ti/Ni multimetallic system: Heck- or reductive-type cyclization reactions of alkyl iodides.

A versatile Ti/Ni multimetallic protocol is described for the efficient catalysis of two different reactions, namely a Heck- and reductive-type cyclization of alkyl iodides, in the absence or presence of water, respectively. Noteworthy, the versatility of Ti(III) chemistry allows an oxidative ending step under reductive conditions to give Heck-type products, and the good H-atom transfer capabilities of Ti(III)-aqua complexes ensure reductive-type cyclizations.

A Small Molecule that Walks Non‐Directionally Along a Track Without External Intervention

Charge of the light brigade: A molecule is able to walk back and forth upon a five-foothold pentaethylenimine track without external intervention. The 1D random walk is highly processive (mean step number 530) and exchange takes place between adjacent amine groups in a stepwise fashion. The walker performs a simple task whilst walking: quenching of the fluorescence of an anthracene group sited at one end of the track. Copyright

Ti/Pd Bimetallic Systems for the Efficient Allylation of Carbonyl Compounds and Homocoupling Reactions

The allylation, crotylation and prenylation of aldehydes and ketones with stable and easily handled allylic carbonates is promoted by a Ti/Pd catalytic system. This Ti/Pd bimetallic system is especially convenient for the allylation of ketones, which are infrequent substrates in other related protocols, and can be carried out intramolecularly to yield five- and six-membered cyclic products with good stereoselectivities. In addition, Ti/Pd-mediated reductions and Würtz-type dimerisation reactions can be readily carried out from allyl carbonates and carboxylates.

Carbocations or Cyclopropyl Gold Carbenes in Cyclizations of Enynes

Theoretical and experimental studies on the gold(I)-catalyzed formal [4+2] cycloaddition of dienynes are consistent with a mechanism that proceeds by means of cyclopropyl gold(I) carbenes instead of simple carbocations. This work shows that homoallylic stabilization is significant even for systems in which the tertiary carbocation is stabilized by two methyl groups.

One-dimensional random walk of a synthetic small molecule toward a thermodynamic sink.

We report on the spontaneous intramolecular migration of α-methylene-4-nitrostyrene from amine group to amine group along oligoethyleneimine tracks up to eight repeat units in length (number of amine footholds, n = 3, 5, 9). Each track consists of n - 1 aliphatic secondary amine footholds plus a naphthylmethylamine group foothold situated at one end of the track. Under basic conditions the α-methylene-4-nitrostyrene unit undergoes a series of reversible intramolecular Michael-retro-Michael reactions between adjacent amine groups that move it up and down the track. For n = 3 and 5 it is possible to monitor the population of every positional isomer on the track by (1)H NMR spectroscopy. On the longest track (n = 9) the fraction of walkers on each end-foothold can be quantified with respect to those on the inner footholds. In all cases the naphthylmethylamine foothold acts as a thermodynamic sink with the steady-state distribution significantly biased in favor of the walker at that site. The dynamics of the walker migration is well described by the random walk of a Brownian particle in one dimension.