-Lithiobenzyl ethers, generated by selective -lithiation, undergo an Aldol-Tishchenko reaction upon treatment with carboxylic esters and paraformaldehyde. The reaction of the organolithium with the carboxylate generates an intermediate enolate that, after formaldehyde addition, affords 1,2,3-triol derivatives in a straightforward and one-pot manner. These products are obtained as single diastereoisomers bearing a quaternary stereocenter. The complete diastereocontrol of the Aldol-Tishchenko process is attributed to stereoelectronic preferences in the transition state.

The -lithiobenzyloxy group, easily generated from aryl benzyl ethers by selective -lithiation with t-BuLi at low temperature, behaves as a directed metalation group (DMG) providing a straight access to o-lithiophenyl -lithiobenzyl ethers. This ortho-directing effect is reinforced in substrates bearing an additional methoxy group at the meta position. The generated dianions can be reacted with a selection of electrophiles including carboxylic esters and dihalosilanes or germanes, which afford interesting benzofuran, sila(germa)dihydrobenzofuran and silachroman derivatives from simple aryl benzyl ethers.

A straightforward and transition metal-free one-pot protocol to synthesize halobenzo[b]furans has been developed employing simple and easily available starting materials such as O-aryl carbamates and alkynylsulfones. The fine-tuning of the different steps involved was key to achieving a successful one-pot procedure. Initially, a directed ortho-lithiation process, which uses the carbamate as the directed metalation group, was crucial in providing access to O-2-alkynylaryl N,N-diethyl carbamates by a direct alkynylation of the o-lithiated carbamate, with arylsulfonylalkynes as electrophilic reagents. Cyclization of the generated o-alkynylaryl carbamates was successfully accomplished through a strategy involving in situ carbamate alkaline hydrolysis under conventional heating or microwave irradiation, coupled with a subsequent heterocyclization step delivering the desired benzo[b]furans. A wide variety of new halobenzo[b]furans has been synthesized and their utility has been demonstrated by their further transformation.

The reactions of o-lithiated O-aryl N,N-diethylcarbamates with different CN multiple bond electrophiles have been thoroughly studied. A 1,5-O→N carbamoyl shift, a new variation of the anionic Fries-type rearrangement, takes place when nitriles, imines or alkylcarbodiimides are employed. In these cases, the carbamoyl group plays a dual role as directing group and building up a variety of functional groups through the 1,5-O→N carbamoyl migration. On the other hand, the use of iso(thio)cyanates and arylcarbodiimides led to non-rearranged o-functionalized O-arylcarbamates.This reactivity was further computationally explored, and the governing factor could be traced back to the relative basicity of the alternative products (migrated vs non-migrated substrates). This exploration also provided interesting insight about the degree of complexation of the lithium cation onto these substrates. A new access to useful 2-hydroxybenzophenone derivatives has also been developed.

α-Oxyketones, easily accessible by conventional routes, can be selectively deprotonated generating an enolate intermediate, which upon treatment with paraformaldehyde undergoes an aldol-Tishchenko reaction, leading to relevant 1,2,3-triol fragments in a totally diastereoselective manner. The excellent stereocontrol in the generation of a quaternary stereocenter is attributed to stereoelectronic effects in the Evans intermediate. This methodology allows overcoming some limitations of our previously reported strategy, based on the reaction of α-lithiobenzyl ethers with esters and paraformaldehyde, broadening the scope of the obtained polyols. Synthetic applications of this process include the preparation of a new dilignol model and some functionalized oxetanes.