Tailor-made molecules – a method for low-cost materials

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Basics:
Multi-Function Component Reactions (MFCRs)

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By extending Multi-Component Reactions (MCRs) through additional orthogonal functional groups in the components the reaction space expands by one or more dimensions [53,58].

Orthogonal one-pot reactions of the kind described above containing 4 components and 5 functional groups in which two orthogonal functions (strongly nucleophilic –NC and strongly electrophilic –NCO) of the same component select their reaction partners from the reaction mixture as well as react with them in an addition reaction and simultaneously in a Passerini reaction (P-5F3CR) as a MFCR to form two new moieties (carbamate and acyl a-oxy carboxylic amide) in one target molecule [51,53,54,58,63].

Isocyanato-Isocyanides (I-Is) are a novel class of compounds containing 2 orthogonal functions for various applications, among them as a component which can extend dimensions in MFCR chemistry [51,53,54,58]. They can be formed of diamino compounds using their monoformamides as well as dehydration and carbonylation with phosgene in a 2-step-reaction. At room temperature, their stability is insufficient. At a temperature of -20°C, however, they can be stored for several weeks without a noticeable deterioration of the active functions (isocyanate and isocyanide).

 

Capabilities:
Large number of products

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Numbers of products (P) in different multi(function)component reactions (MCR/MFCR) depending on numbers of starting material sets (STM-S)

STM-S

MCR/MFCR 2           4 10 30 100
P-3CR[a] 8 64 1.000 27.000 1.000.000
U-4CR[b] 16 256 10.000 810.000 100.000.000
P-5F4CR[c] 32 1.024 100.000 24.300.000 10.000.000.000
…2CR [d] 4 16 100 900 10.000

[a] Passerini-3componentreaction
[b] Ugi-4componentreaction
[c] Passerini-5function4componentreaction
[d] For comparison: »classical« A + B reactions

Capabilities:
Simplified synthesis – fewer reaction steps required

Compared to MCRs, MFCRs allow for an additional reduction of reaction steps, thereby saving a lot of time and decreasing production costs. Moreover, MFCRs are a useful tool for diversity oriented syntheses (DOS) and combinatorial chemistry.

Research of literature using Scifinder regarding the generation of large moieties (marked in red) through parallel addition/Passerini reactions in MFCRs based on lysine (P-5F3CR) returns syntheses of a patented compound (DE3407473, 1965, left side) and a large moiety of the natural product lysine-valinomycin (right side) – in one reaction step each.


Prediction:

Due to the large product variety of MCRs and the potentiating effect caused by the additional functional groups we expect that by combining dozens of MFCRs with each other, most highly complex organic compounds can be produced with few reaction steps – allowing for low costs.