Abstract
Among all strategies used by organic chemists to control the stereoselectivity of reactions, organocatalysis, which consists in using the chirality of a small organic molecule, is an increasingly popular method. The prolinecatalyzed aldol reaction was one of the first reported cases that demonstrated the power of organocatalysis in the field of asymmetric synthesis. Previous theoretical contributions focused on the reaction mechanism using quantum mechanics (QM) methods. We here present a theoretical study about one specific step of the proline-catalyzed aldol reaction, namely, the conversion of the iminium intermediate into the corresponding enamine. It consists of an intramolecular rearrangement that involves the transfer of a hydrogen atom. First, we investigate this transfer using modern QM models, that is, density functional theory calculations with the M06-2X functional. On the basis of these QM results, we then assess the performance of a reactive force field, ReaxFF, used in combination with molecular dynamics simulations in order to provide a complementary light on this reaction.
| Original language | English |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Theoretical Chemistry Accounts |
| Volume | 131 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 9 Aug 2012 |
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Keywords
- DFT
- Enamine
- Force field development
- Iminium
- M06-2X
- Molecular dynamics simulation
- Organocatalysis
- Proline catalysis
- Reaction pathway
- ReaxFF
- Solvent effects
Cite this
}
Ab initio quantum chemical and ReaxFF-based study of the intramolecular iminium-enamine conversion in a proline-catalyzed reaction. / Hubin, Pierre O.; Jacquemin, Denis; Leherte, Laurence; André, Jean Marie; van Duin, Adri C T; Vercauteren, Daniel P.
In: Theoretical Chemistry Accounts, Vol. 131, No. 8, 09.08.2012, p. 1-11.Research output: Contribution to journal › Article
TY - JOUR
T1 - Ab initio quantum chemical and ReaxFF-based study of the intramolecular iminium-enamine conversion in a proline-catalyzed reaction
AU - Hubin, Pierre O.
AU - Jacquemin, Denis
AU - Leherte, Laurence
AU - André, Jean Marie
AU - van Duin, Adri C T
AU - Vercauteren, Daniel P.
PY - 2012/8/9
Y1 - 2012/8/9
N2 - Among all strategies used by organic chemists to control the stereoselectivity of reactions, organocatalysis, which consists in using the chirality of a small organic molecule, is an increasingly popular method. The prolinecatalyzed aldol reaction was one of the first reported cases that demonstrated the power of organocatalysis in the field of asymmetric synthesis. Previous theoretical contributions focused on the reaction mechanism using quantum mechanics (QM) methods. We here present a theoretical study about one specific step of the proline-catalyzed aldol reaction, namely, the conversion of the iminium intermediate into the corresponding enamine. It consists of an intramolecular rearrangement that involves the transfer of a hydrogen atom. First, we investigate this transfer using modern QM models, that is, density functional theory calculations with the M06-2X functional. On the basis of these QM results, we then assess the performance of a reactive force field, ReaxFF, used in combination with molecular dynamics simulations in order to provide a complementary light on this reaction.
AB - Among all strategies used by organic chemists to control the stereoselectivity of reactions, organocatalysis, which consists in using the chirality of a small organic molecule, is an increasingly popular method. The prolinecatalyzed aldol reaction was one of the first reported cases that demonstrated the power of organocatalysis in the field of asymmetric synthesis. Previous theoretical contributions focused on the reaction mechanism using quantum mechanics (QM) methods. We here present a theoretical study about one specific step of the proline-catalyzed aldol reaction, namely, the conversion of the iminium intermediate into the corresponding enamine. It consists of an intramolecular rearrangement that involves the transfer of a hydrogen atom. First, we investigate this transfer using modern QM models, that is, density functional theory calculations with the M06-2X functional. On the basis of these QM results, we then assess the performance of a reactive force field, ReaxFF, used in combination with molecular dynamics simulations in order to provide a complementary light on this reaction.
KW - DFT
KW - Enamine
KW - Force field development
KW - Iminium
KW - M06-2X
KW - Molecular dynamics simulation
KW - Organocatalysis
KW - Proline catalysis
KW - Reaction pathway
KW - ReaxFF
KW - Solvent effects
UR - http://www.scopus.com/inward/record.url?scp=84864773637&partnerID=8YFLogxK
U2 - 10.1007/s00214-012-1261-4
DO - 10.1007/s00214-012-1261-4
M3 - Article
AN - SCOPUS:84864773637
VL - 131
SP - 1
EP - 11
JO - Theoretical Chemistry Accounts: Theory, Computation, and Modeling
JF - Theoretical Chemistry Accounts: Theory, Computation, and Modeling
SN - 1432-881X
IS - 8
ER -