Methodologies, tools for synthesis - Cascade/multicomponent reactions & multistep synthesis

[3,3]-Allyl cyanate sigmatropic rearrangement as key steps of tandem processes

An efficient asymmetric synthesis of α-amino allylsilane derivatives is based on a [3,3]-allyl cyanate sigmatropic rearrangement from enantioenriched γ-hydroxy alkenylsilyl compounds. The isocyanate intermediate can be trapped by several nucleophiles, opening the way for the preparation of unknown chiral functionalized compounds such as the α-ureido allylsilanes as well as carbamate derivatives. A computational study was conducted to rationalize the complete 1,3-chirality transfer of this kind of rearrangement.


Allyl cyanate sigmatropic rearrangement

An unexpected 1,3-dioxa-[3,3]-sigmatropic rearrangement occurred during the treatment of aryl- and alkenyl-substituted allylic alcohols with activated isocyanates. The reorganization of bonds is highly dependent on the electron density of the aromatic ring and the nature of isocyanate used. This metal-free tandem process from branched allyl alcohols was initiated by a carbamoylation reaction followed by a sigmatropic rearrangement thus giving a new access to (E)-cinnamyl and conjugated (E,E)-diene carbamates, such as N-acyl and N-sulfonyl derivatives. A computational study was conducted in order to rationalize this phenomenon, and a rearrangement progress kinetic analysis was performed.

sigmatropic rearrangement


Dendralenes, which in recent years have received increasing attention as building blocks for multiple Diels–Alder cycloadditions and rapid generation of molecular complexity. These acyclic cross-conjugated polyenes are particularly well-suited to diversity-oriented synthesis (DOS), a promising strategy for lead generation in chemical genetics and drug discovery.

On the basis of these precedents, we explored the synthesis and reactivity of acyclic 2-vinyl α,β-unsaturated aldehydes, imines and hydrazones, which we named [3]-1-heterodendralenes by analogy with the corresponding carbotrienes. These compounds have proven to be useful and versatile building blocks for rapid access to a rich structural diversity with control of multiple stereocenters. 


The range of accessible scaffolds can be greatly extended by selecting the substituents of the starting heterodendralenes (R, Y) and the reactants engaged in the successive elementary steps. Skeletal diversity can be increased by combining the reaction partners in a different sequential order.



9-Hydroxyfluorenes constitute the common substructure of a number of biologically active substances. They have been are easily synthesized via a tandem Suzuki/phenolic aldolisation sequence. This process was extended to 9-aminofluorenes by simply adding various amines as third partners. 


For more information : Fabienne Berrée, François Carreaux