TY - JOUR
T1 - Structural Features of Diacyldodecaheterocycles with Pseudo-C2-Symmetry
T2 - Promising Stereoinductors for Divergent Synthesis of Chiral Alcohols
AU - Flores-Bernal, Gustavo G.
AU - Vargas-Díaz, Ma Elena
AU - Jiménez-Vázquez, Hugo A.
AU - Hernández-Rodríguez, Marcos
AU - Zepeda-Vallejo, L. Gerardo
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/6/13
Y1 - 2023/6/13
N2 - Pseudo-C2-symmetric dodecaheterocyclic structures, which possess two acyl/aroyl groups disposed on either a cis- or trans-relative configuration, were prepared from the naturally occurring (−)-(1R)-myrtenal. Addition of Grignard reagents (RMgX) to the diastereoisomeric mixture of these compounds unexpectedly showed that nucleophilic additions to the two prochiral carbonyl centers gave the same stereochemical result in both cis/trans diastereoisomers, making unnecessary the separation of this mixture. Noticeably, both carbonyl groups showed different reactivity because one of them is attached to an acetalic carbon and the other to a thioacetalic carbon. Furthermore, addition of RMgX to the carbonyl attached to the former carbon takes place through the re face, while addition to the second one proceeds through the si face, thus affording the corresponding carbinols in a highly diastereoselective process. This structural feature allowed the sequential hydrolysis of both carbinols, yielding separately (R)- and (S)-1,2-diols after reduction with NaBH4. The mechanism of the asymmetric Grignard addition was explained by density functional theory calculations. This approach contributes to the development of the divergent synthesis of structurally and/or configurationally different chiral molecules.
AB - Pseudo-C2-symmetric dodecaheterocyclic structures, which possess two acyl/aroyl groups disposed on either a cis- or trans-relative configuration, were prepared from the naturally occurring (−)-(1R)-myrtenal. Addition of Grignard reagents (RMgX) to the diastereoisomeric mixture of these compounds unexpectedly showed that nucleophilic additions to the two prochiral carbonyl centers gave the same stereochemical result in both cis/trans diastereoisomers, making unnecessary the separation of this mixture. Noticeably, both carbonyl groups showed different reactivity because one of them is attached to an acetalic carbon and the other to a thioacetalic carbon. Furthermore, addition of RMgX to the carbonyl attached to the former carbon takes place through the re face, while addition to the second one proceeds through the si face, thus affording the corresponding carbinols in a highly diastereoselective process. This structural feature allowed the sequential hydrolysis of both carbinols, yielding separately (R)- and (S)-1,2-diols after reduction with NaBH4. The mechanism of the asymmetric Grignard addition was explained by density functional theory calculations. This approach contributes to the development of the divergent synthesis of structurally and/or configurationally different chiral molecules.
UR - http://www.scopus.com/inward/record.url?scp=85159622647&partnerID=8YFLogxK
U2 - 10.1021/acsomega.3c01161
DO - 10.1021/acsomega.3c01161
M3 - Artículo
C2 - 37332815
AN - SCOPUS:85159622647
SN - 2470-1343
VL - 8
SP - 20611
EP - 20620
JO - ACS Omega
JF - ACS Omega
IS - 23
ER -