Improved heteroatom nucleophilic addition to electron-poor alkenes promoted by CeCl3.7H2O/NaI system supported on alumina in solvent-free conditions.

Conjugate addition of heteroatom nucleophiles to carbon-carbon double bonds conjugated with a strong electron-withdrawing group is one of the most important new bond-forming strategies in synthetic organic chemistry. Among the methods for these Michael additions, Lewis acids have shown the best promoter activity, and in particular, the use of reagents impregnated over inorganic supports is rapidly increased. With the increase of environmental consciousness in chemical research, the solvent-free Michael addition has attracted our attention. In continuation of our ongoing program to develop synthetic protocols utilizing cerium trichloride, we report an extension of the CeCl(3).7H(2)O/NaI combination supported under solvent-free conditions to promote heteroatom Michael addition. Using neutral alumina (Al(2)O(3)) as solid support permits us to circumvent some of the problems associated with the procedure where the inorganic support is silica gel. The CeCl(3).7H(2)O/NaI/Al(2)O(3) system works well for hetero-Michael additions utilizing weakly nucleophiles such as imidazoles and carbamates, and also the reaction proceeds with good yields in the case of Michael acceptors different from alpha,beta-unsaturated carbonyl compounds. An important synthetic application of this our methodology is the intramolecular aza-Michael reaction in producing 4-piperidinone derivatives, which are of interest as synthetic intermediates toward important classes of heterocycles.

Asymmetric aminolysis of aromatic epoxides: a facile catalytic enantioselective synthesis of anti-beta-amino alcohols.

[reaction: see text] The first asymmetric aminolysis of trans-aromatic epoxides with anilines is described. The process affords enantioenriched anti-beta-amino alcohols in up to 99% ee. The complete regio- and diastereoselectivity observed uses commercially available [Cr(Salen)Cl] as a Lewis acid catalyst and in combination with a very simple experimental procedure renders the present reaction a facile and practical tool for the synthesis of chiral nonracemic anti-beta-amino alcohols.

Conformational studies by dynamic NMR. 98. Stereodynamics of bond rotation in beta-hydroxyesters.

The dynamic processes due to restricted intramolecular motions have been observed in a number of variously substituted beta-hydroxyesters by variable-temperature NMR spectroscopy. The barriers for three such processes (i.e. Ph-C, t-Bu-C, and C(alpha)-C(beta) bond rotation) have been measured.

Conformational studies by dynamic NMR. 88.(1) stereomutation processes in the diastereoisomers of a representative amino alcohol and related amide precursors.

The barriers for three internal motions (i.e., phenyl and tert-butyl rotation as well as N-inversion) have been determined by dynamic NMR spectroscopy in the two diastereoisomeric forms of a typical amino alcohol [dimethylamino-2,4,4-trimethyl-3-phenyl-3-pentanol, Me(2)NCH(2)CHMeC(OH)PhBu(t)]. The two structures were assigned by connection with those of the corresponding amide precursors determined by single-crystal X-ray diffraction. These amides (C=O in place of CH(2)) too were found to undertake internal motions amenable to NMR observation, i.e., phenyl, tert-butyl, and N-CO rotations: the corresponding barriers were also measured. Ab initio computations indicate that H-bonding makes all these molecules adopt six-membered cyclic conformations, a conclusion which agrees well with the X-ray crystal structure determined for the amide precursors.