Planar Chirality Directs Enantiospecific Diastereoselectivity in Isocyanide-Based Multicomponent Reactions
Abstract
Stereochemical control in isocyanide-based multicomponent reactions (IMCRs) remains a fundamental challenge, particularly in substrate-controlled variants. Here we show that planar chirality embedded within [2.2]paracyclophane scaffolds enables predictable enantiospecific stereochemical transfer across the Passerini three-component reaction as well as the Ugi fourcomponent and Ugi-tetrazole manifolds. Each enantiomer of the planar-chiral substrate stereospecifically transfers its configuration to the product, establishing a deterministic relationship between substrate and product stereochemistry. Across more than 65 reactions, this strategy provides consistent diastereocontrol without external chiral catalysts. These findings establish planar chirality as a general substrate-encoded principle for stereochemical control in IMCRs and expand the scope of enantiospecific multicomponent synthesis beyond classical point chirality.
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BibTeX
@article{kapsalis2026planar,
title = {{Planar Chirality Directs Enantiospecific Diastereoselectivity in Isocyanide-Based Multicomponent Reactions}},
author = {Michael Kapsalis and Michael Fragkiadakis and Iakovos Konstantaras and Konstantinos G Froudas and Taxiarchis Stergiannakos and Rongyu Sun and Erica Benedetti and Constantinos G Neochoritis},
journal = {ACS Organic \& Inorganic Au},
year = {2026},
month = may,
doi = {10.1021/acsorginorgau.6c00034},
url = {https://hal.science/hal-05762854v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Planar Chirality Directs Enantiospecific Diastereoselectivity in Isocyanide-Based Multicomponent Reactions
AU - Michael Kapsalis
AU - Michael Fragkiadakis
AU - Iakovos Konstantaras
AU - Konstantinos G Froudas
AU - Taxiarchis Stergiannakos
AU - Rongyu Sun
AU - Erica Benedetti
AU - Constantinos G Neochoritis
PY - 2026
DA - 2026/05/26
JO - ACS Organic & Inorganic Au
DO - 10.1021/acsorginorgau.6c00034
UR - https://hal.science/hal-05762854v1
AB - Stereochemical control in isocyanide-based multicomponent reactions (IMCRs) remains a fundamental challenge, particularly in substrate-controlled variants. Here we show that planar chirality embedded within [2.2]paracyclophane scaffolds enables predictable enantiospecific stereochemical transfer across the Passerini three-component reaction as well as the Ugi fourcomponent and Ugi-tetrazole manifolds. Each enantiomer of the planar-chiral substrate stereospecifically transfers its configuration to the product, establishing a deterministic relationship between substrate and product stereochemistry. Across more than 65 reactions, this strategy provides consistent diastereocontrol without external chiral catalysts. These findings establish planar chirality as a general substrate-encoded principle for stereochemical control in IMCRs and expand the scope of enantiospecific multicomponent synthesis beyond classical point chirality.
SN - 2694-247X
ER -