Sara López‐Tosco

Acetylides from Alkyl Propiolates as Building Blocks for C3 Homologation

Alkyl propiolates are reagents with a versatile reactivity profile that entirely remains in the C(3)-homologated product for further elaboration. To be effective, this C(3) homologation requires suitable methods for the generation of the acetylide anion that are compatible with both the conjugated ester and the electrophilic partner. Recent advances include catalytic procedures for the in situ generation of these acetylides in the presence of suitable electrophiles. Whereas the organometallic methods have brought stereoselectivity to these reactions, the organocatalytic methods laid the ground for new efficient domino processes that generate complexity.

From Conjugated Tertiary Skipped Diynes to Chain-Functionalized Tetrasubstituted Pyrroles

Authors thank the Spanish Ministerio de Educacion y Ciencia and the European Regional Development Fund (CTQ2005-09074-C02-02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), CSIC (Proyecto Intramural Especial 200719) and Fundacion Instituto Canario de Investigacion del Cancer (FICI-G.I. No.u200508/2007) for financial support. S.L.-T. Thanks MEC for a FPU grant.

Synthesis of fully substituted pyrimidines.

A novel approach to the synthesis of fully substituted pyrimidine derivatives armed with an oxy-functionalized acetate chain at the ring is described. The manifold uses amidines as the nitrogen source and activated skipped diynes as the electrophilic reactive partners in a coupled domino strategy. In the first domino reaction, two consecutive aza-Michael additions assemble the six-membered ring heterocycle, while in the second domino process, a [H]-shift and a [3,3]-sigmatropic rearrangement lead to the aromatization of the product.

Tertiary skipped diynes: A pluripotent building block for the modular and diversity-oriented synthesis of nitrogen heterocycles

This research was supported by the Spanish Ministerio de Ciencia e Innovacion, the European Regional Development Fund (CTQ2008-06806-C02-02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), FUNCIS (REDESFAC PI01/06) and the Fundacion Instituto Canario de Investigacion del Cancer (FICI-G.I.N808/2007). S.L.-T. thanks the Spanish MEC for an FPU grant. The authors thank technician Anna Jurado Varona for her experimental assistance.

Diverted domino reactivity in tertiary skipped diynes: A convenient access to polyfunctionalized cyclohexadienones and multivalent aromatic scaffolds

This research was supported by the Spanish MICINN and the European RDF (CTQ2008–06806-C02–02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), FUNCIS (PI 43/09). S. L.-T. thanks the Spanish MEC for a FPU grant. The authors thank technician Ms. Anna Jurado Varona for her experimental assistance.

Propargyl Vinyl Ethers and Tertiary Skipped Diynes: Two Pluripotent Molecular Platforms for Diversity-Oriented Synthesis

During the last years, we have been involved in the development of a diversity-oriented synthetic strategy aimed at transforming simple, linear, and densely functionalized molecular platforms into collections of topologically diverse scaffolds incorporating biologically relevant structural motifs such as N- and O- heterocycles, multifunctionalized aromatic rings, fused macrocycles, etc. The strategy merges the concepts of pluripotency (the property of an array of chemical functionalities to express different chemical outcomes under different chemical environments) and domino chemistry (chemistry based on processes involving two or more bond-forming transformations that take place while the initial reaction conditions are maintained, with the subsequent reaction resulting as a consequence of the functionality installed in the previous one) to transform common multifunctional substrates into complex and diverse molecular frameworks. This design concept constitutes the ethos of the so-called branching cascade strategy, a branch of diversity-oriented synthesis focused on scaffold diversity generation. Two pluripotent molecular platforms have been extensively studied under this merging (branching) paradigm: C4-O-C3 propargyl vinyl ethers (PVEs) and C7 tertiary skipped diynes (TSDs). These are conveniently constructed from simple and commercially available raw materials (alkyl propiolates, ketones, aldehydes, acid chlorides) through multicomponent manifolds (ABB three-component reaction for PVEs; A2BB four-component reaction for TSDs) or a simple two-step procedure (for PVEs). Their modular origin facilitates their structural/functional diversification without increasing the number of synthetic steps for their assembly. These two pluripotent molecular platforms accommodate a well-defined and dense array of through-bond/through-space interrelated functionalities on their structures, which defines their primary reactivity principles and establishes the reactivity profile. The PVEs are defined by the presence of an alkyne (alkynoate) function and a conjugated enol moiety and their mutual through-bond/through-space connectivity. This functional array accommodates a number of domino reactions launched either by a Michael addition on the alkynoate moiety (conjugated alkynes) or by a [3,3]-propargyl Claisen rearrangement (conjugated and nonconjugated alkynes). The reactivity profile of the TSDs is defined by the two connected alkynoate moieties (Michael addition) and the bispropargylic ester group ([3,3]-sigmatropic rearrangement). Using these first reactivity principles, each platform selectively delivers one unique and different skeleton (topology) from each domino transformation. Thus, through the use of 11 instrumentally simple and scalable domino reactions, we have transformed these two linear (rod-symmetric) pluripotent molecular platforms into 16 different scaffolds incorporating important structural motifs and multifunctional decorative patterns. The generated scaffolds entail carbocycles, heterocycles, aromatics, β,γ-unsaturated esters and acids, and fused polycycles. They can be transformed into more elaborated molecular skeletons by the use of chemical handles generated in their own domino reactions or by appending different functionalities to the pluripotent molecular platform (secondary reactivity principles).

Ab initio crystal structure determination of two chain functionalized pyrroles from synchrotron X-ray powder diffraction data

The financial support from the Spanish Ministerio de Ciencia e Innovacion (PI201060E013) is also acknowledged.