4 research outputs found
Transfer of 1âAlkenyl Groups between Secondary Amines. Relative Stability and Reactivity of Enamines from Popular Organocatalysts
Enamines
from 3-methylbutanal and several Pro- and Phe-derived
secondary amines were prepared in DMSO-<i>d</i><sub>6</sub>, CD<sub>3</sub>CN, and CDCl<sub>3</sub>. For the first time, the
relative thermodynamic stabilities of these and other enamines were
compared, and rapid exchanges of 1-alkenyl groups were demonstrated.
Competition experiments showed that the most favored enamines (without
significant steric inhibition of resonance) react more rapidly with
electrophiles
Importance of the Electron Correlation and Dispersion Corrections in Calculations Involving Enamines, Hemiaminals, and Aminals. Comparison of B3LYP, M06-2X, MP2, and CCSD Results with Experimental Data
While
B3LYP, M06-2X, and MP2 calculations predict the Î<i>G</i>° values for exchange equilibria between enamines
and ketones with similar acceptable accuracy, the M06-2X/6-311+GÂ(d,p)
and MP2/6-311+GÂ(d,p) methods are required for enamine formation reactions
(for example, for enamine <b>5a</b>, arising from 3-methylbutanal
and pyrrolidine). Stronger disagreement was observed when calculated
energies of hemiaminals (<i>N</i>,<i>O</i>-acetals)
and aminals (<i>N</i>,<i>N</i>-acetals) were compared
with experimental equilibrium constants, which are reported here for
the first time. Although it is known that the B3LYP method does not
provide a good description of the London dispersion forces, while
M06-2X and MP2 may overestimate them, it is shown here how large the
gaps are and that at least single-point calculations at the CCSDÂ(T)/6-31+GÂ(d)
level should be used for these reaction intermediates; CCSDÂ(T)/6-31+GÂ(d)
and CCSDÂ(T)/6-311+GÂ(d,p) calculations afford Î<i>G</i>° values in some cases quite close to MP2/6-311+GÂ(d,p) while
in others closer to M06-2X/6-311+GÂ(d,p). The effect of solvents is
similarly predicted by the SMD, CPCM, and IEFPCM approaches (with
energy differences below 1 kcal/mol)
Relative Tendency of Carbonyl Compounds To Form Enamines
Equilibria between carbonyl compounds and their enamines (from <i>O</i>-TBDPS-derived prolinol) have been examined by NMR spectroscopy in DMSO-<i>d</i><sub>6</sub>. By comparing the exchange reactions between pairs (enamine A + carbonyl B â carbonyl A + enamine B), a quite general scale of the tendency of carbonyl groups to form enamines has been established. Aldehydes quickly give enamines that are relatively more stable than those of ketones, but there are exceptions to this expected rule; for example, 1,3-dihydroxyacetone acetals or 3,5-dioxacyclohexanones (2-phenyl-1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one) show a greater tendency to afford enamines than many α-substituted aldehydes
Total Synthesis of Amphidinolide K, a Macrolide That Stabilizes FâActin
The total synthesis of (â)-amphidinolide
K (<b>1</b>) based on asymmetric addition of allylsilane <b>C1</b>â<b>C8</b> to enal <b>C9</b>â<b>C22</b> is reported.
The 1,9,18-tris-<i>O</i>-TBDPS ether was converted into
the desired 9,18-dihydroxy acid. Its macrolactonization was accomplished
by the Shiina method. Compound <b>1</b> together with some of
its stereoisomers and analogues were subjected to evaluation of the
possible disruption of the α,ÎČ-tubulinâmicrotubule
and/or G-actinâF-actin equilibria. Compound <b>1</b> behaves
as a stabilizer of actin filaments (F-actin) in vitro