End-to-End Automated Synthesis of C(sp)-Enriched Drug-like Molecules Negishi Coupling and Novel, Automated Liquid-Liquid Extraction.

Herein, we report an end-to-end process including synthesis, work-up, purification, and post-purification with minimal human intervention using Negishi coupling as a key transformation to increase Fsp in bioactive molecules. The main advantages of this protocol are twofold. First, the automated sequential generation of organozinc reagents from readily available alkyl halides offers a large diversity of alkyl groups to functionalize (hetero)aryl halide scaffolds Pd-catalyzed Negishi coupling in continuous flow.

Gold- or platinum-catalyzed cascade processes of alkynol derivatives involving hydroalkoxylation reactions followed by Prins-type cyclizations.

An efficient method for the synthesis of [3.3.1]bicyclic compounds from easily available alkynol derivatives has been developed.

[W(CO)5]-catalyzed endo- or exo-cycloisomerization reactions of 1,1-disubstituted 4-pentyn-1-ols: experimental and theoretical studies.

The [W(CO)5]-catalyzed cycloisomerization reaction of 1,1-disubstituted 4-pentyn-1-ol derivatives has been studied from both, an experimental and theoretical point of view. Three different catalytic systems have been evaluated {preformed [(thf)W(CO)5], [W(CO)6]/excess Et3N, and [W(CO)6]/2 mol % Et3N]. We have found that the reaction proceeds to give the formal endo- or exo-cycloisomerization products depending on the amount of Et3N used and on the substitution along the alkyl chain of the starting alkynol.

Solvent-assisted new reaction pathways for the (THF)W(CO)5-promoted endo- and exo-cycloisomerization of 4-pentyn-1-ol: a theoretical investigation.

New solvent-assisted mechanistic routes were located for the (THF)W(CO)5-promoted endo- and exo-cycloisomerization of 4-pentyn-1-ol using the B3LYP/6-31G (with the LANL2DZ relativistic pseudopotential for W) theory level. A mixed model was used by explicitly including a THF molecule as a component of the reactive system and taking into account the effect of bulk solvent by means of the PCM-UAHF method. This THF molecule plays a crucial role by making the endo route leading to the cyclic carbene complex the most favorable one because of an important catalytic effect.

One-pot enantioselective formation of eight-membered rings from alkenyl Fischer carbene complexes and ketone enolates.

Eight-membered carbocycles with up to five new stereogenic centers are enantioselectively obtained following a one-pot procedure that involves the coupling of three components: an alkenyl Fischer carbene complex, a ketone enolate, and allyl lithium.