https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Recent developments in isocyanide based multicomponent reactions in applied chemistry

Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Multicomponent reactions (MCRs) are one-pot reactions employing more than two starting materials, e.g. 3, 4, … 7, where most of the atoms of the starting materials are incorporated in the final product.1 Several descriptive tags are regularly attached to MCRs (Fig. 1): they are atom economic, e.g. the majority if not all of the atoms of the starting materials are incorporated in the product; they are efficient, e.g. they efficiently yield the product since the product is formed in one-step instead of multiple sequential steps; they are convergent, e.g. several starting materials combine in one reaction to form the product; they exhibit a very high bond-forming-index (BFI), e.g. several non-hydrogen atom bonds are formed in one synthetic transformation.2 Therefore MCRs are often a useful alternative to sequential multistep synthesis.






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Figure 1


Above: multistep syntheses can be divergent (sequential) or convergent; below: in analogy MCR reactions are convergent and one or two component reactions are divergent or less convergent.

Chemistry and Biology Of Multicomponent Reactions

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

We report a new and effective method for the enantioselective addition of propa-1,2-dienyl and propargyl groups to aldehydes to form chiral alcohols

A practical and general enantioselective synthesis of chiral propa-1,2-dienyl and propargyl carbinols

La diastereoselectivite de la transposition est en accord avec un etat de transition de type chaise

Highly enantioselective and diastereoselective Ireland-Claisen rearrangement of achiral allylic esters

A facile synthesis of N -carbamoylmethyl- α -aminobutyrolactones by the Ugi multicomponent condensation reaction

Pathways for the diastereoselective preparation of chiral 1,2-diaryl-1,2-diaminoethanes from ArCOOH, ArCHO or ArBr are described.

Duck-Hyung Lee

Papers

A practical and general enantioselective synthesis of chiral propa-1,2-dienyl and propargyl carbinols

Highly enantioselective and diastereoselective Ireland-Claisen rearrangement of achiral allylic esters

A facile synthesis of N -carbamoylmethyl- α -aminobutyrolactones by the Ugi multicomponent condensation reaction

Convenient routes to symmetrical benzils and chiral 1,2-diaryl-1,2-diaminoethanes, useful controllers and probes for enantioselective synthesis

An efficient synthesis of morpholin-2-one derivatives using glycolaldehyde dimer by the Ugi multicomponent reaction.