Efficient Amplification in Soai's Asymmetric Autocatalysis by a Transient Stereodynamic Catalyst

Abstract

Mechanisms leading to a molecular evolution and the formation of homochirality in nature are interconnected and a key to the underlying principles that led to the emergence of life. So far proposed mechanisms leading to a non-linear reaction behavior are based mainly on the formation of homochiral and heterochiral dimers. Since homochiral and heterochiral dimers are diastereomers of each other, the minor enantiomer is shifted out of equilibrium with the major enantiomer by dimer formation and thus a reaction or catalysis can be dominated by the remaining molecules of the major enantiomer. In this article a mechanism is shown that leads to homochirality by the formation of a highly catalytically active transient intermediate in a stereodynamically controlled reaction. This is demonstrated by Soai's asymmetric autocatalysis, in which aldehydes are transformed into the corresponding alcohols by addition of dialkylzinc reagents. The mechanism of chirogenesis proposed here shows that an apparently inefficient reaction is the best prerequisite for a selection mechanism. In addition, stereodynamic control offers the advantage that the minor diastereomeric intermediate can be interconverted into the major diastereomer and thus be stereoeconomically efficient. This is supported by computer simulation of reaction kinetics.

One Soai reaction, two mechanisms?

“…33 1 H NMR experiments further proved the strong propensity of pyrimidylaldehydes to form hemiacetals. 44 Finally, extensive kinetic modelling allowed prediction of very strong chiral amplification and of the time of the inflection point as a function of initiator ee. 34,35 For simplicity, the autocatalytic cycle of the (R)-enantiomer has been omitted.…”

Enantioselective Self-Replicators

“…Much more than a simple curiosity of nature, it is essential for the exceptional efficiency in information transfer, − catalysis, and electron transfer of today’s biomolecules and confers directionality to molecular and cellular motion. − Hence, homochirality is likely to play an important role in the emergence of function in the transition from chemistry to biology. ,, How biological homochirality arose from a (close to) racemic world is thus a question that intrigues. In the past decades, the scientific community has devoted much effort to study chiral amplification − and symmetry breaking processes. , Most of these efforts have been directed at the polymerization of peptides and oligonucleotides, − crystallization, , and asymmetric autocatalysis of small molecules, − of which the Soai reaction is a famous example. − An overview of these systems is provided in and . In many instances, autocatalysis plays an important role in the emergence of homochirality.…”

Synthesis and stereodynamics of intramolecular hemiacetals in biaryl aldehyde‐alcohols

“…Besides Soai and coworkers, [9][10][11] the groups of Blackmond, 12 Brown et al, 13,14 and Amedjkouh et al [15][16][17] focused on the elucidation of the Soai reaction by experimental investigations. 18 Recent mechanistic investigations by the groups of Denmark 19,20 and Trapp 21,22 proposed two different mechanistic approaches. 23 In 2020, Denmark et al proposed a homochiral tetramer in a square-macrocycle-square conformation of the product alkoxide as catalytically active species in the Soai reaction.…”

“…23 In 2020, Denmark et al proposed a homochiral tetramer in a square-macrocycle-square conformation of the product alkoxide as catalytically active species in the Soai reaction. 21,22 Trapp et al proposed a different mechanism for the Soai reaction, based on identified hemiacetalate complexes, which are formed from the aldehyde and Zn-alkoxide. The configuration of the Znalkoxides determines the configuration of the newly formed stereogenic center of the hemiacetalate.…”

“…Recent mechanistic investigations by the groups of Denmark 19,20 and Trapp 21,22 proposed two different mechanistic approaches 23 . In 2020, Denmark et al proposed a homochiral tetramer in a square‐macrocycle‐square conformation of the product alkoxide as catalytically active species in the Soai reaction 21,22 . Trapp et al proposed a different mechanism for the Soai reaction, based on identified hemiacetalate complexes, which are formed from the aldehyde and Zn‐alkoxide.…”