Computational Insight into 1,2-Diamine, -Diether, and -Amino Ether Chiral Ligand-Mediated Carbolithiation: A Case of Enantioinduction Reversal.

trans-1,2-Cyclohexanediamine, -diether, and -amino ether were compared as chiral inducers in the asymmetric intramolecular carbolithiation of olefinic aryllithiums. Switching from diamine to ethereal ligands inverts the sense of asymmetric induction. This reversal of stereoselectivity was investigated through density functional theory calculations. High enantioselectivities observed with diether and amino ether ligands arise from favorable weak interactions between the ligand and the substrate. The relative efficiency of the three ligands and sense of stereoinduction for the most efficient diether and amino ether ligands prove to be foreseeable by modeling the reaction with the parent achiral 1,2-bidentate additives and comparing the diastereomeric transition states stemming from the two half-chair conformations of their lithium chelate.

Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation.

A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring α-amino- or α-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular carbolithiation reactions, outperforming the benchmark ligand (-)-sparteine. The ligand could be used in a substoichiometric amount (0.25 equiv) without significant loss of enantioselectivity.

Radical Cyclisation of α-Halo Aluminium Acetals: A Mechanistic Study.

α-Bromo aluminium acetals are suitable substrates for Ueno-Stork-like radical cyclisations affording γ-lactols and acid-sensitive methylene-γ-lactols in high yields. The mechanistic study herein sets the scope and limitation of this reaction. The influence of the halide (or chalcogenide) atom X (X=Cl, Br, I, SPh, SePh) in the precursors α-haloesters, as well as influence of the solvent and temperature was studied. The structure of the aluminium acetal intermediates resulting from the reduction of the corresponding α-haloesters has been investigated by low-temperature (13) C-INEPT diffusion-ordered NMR spectroscopy (DOSY) experiments and quantum calculations, providing new insights into the structures of these thermally labile intermediates. Oxygen-bridged dimeric structures with a planar Al2 O2 ring are proposed for the least hindered aluminium acetals, while monomeric structures seem to prevail for the most hindered species. A comparison against the radical cyclisation of aluminium acetals derived from allyl and propargyl alcohols with the parent Ueno-Stork has been made at the BHandHLYP/6-311++G(d,p) level of theory, highlighting mechanistic similarities and differences.

Synthesis of Polysubstituted γ-Butenolides via a Radical Pathway: Cyclization of α-Bromo Aluminium Acetals and Comparison with the Cyclization of α-Bromoesters at High Temperature.

Polysubstituted butenolides were obtained in good to high yields from α-bromoesters derived from propargyl alcohols by a one-pot reaction involving the radical cyclization of α-bromo aluminium acetals, followed by the oxidation of the resulting cyclic aluminium acetals in an Oppenauer-type process and migration of the exocyclic C=C bond into the α,ß-position. Comparison with the direct cyclization of α-bromoesters at high temperature and under high dilution conditions is described. Deuterium-labelling experiments allowed us to uncover "invisible" 1,5-hydrogen atom transfers (1,5-HATs) that occur during these cyclization processes, together with the consequences of the latter in the epimerization of stereogenic centres. Compared to the classical approach, the cyclization of aluminium acetals proved to be highly chemoselective and its efficiency was illustrated by the short total syntheses of optically enriched γ-butenolides isolated from Plagiomnium undulatum and from Kyrtuhrix maculans.

Chemoselective deprotonative lithiation of azobenzenes: reactions and mechanisms.

Whereas standard strong bases (n-BuLi, s-BuLi/TMEDA, n-BuLi/t-BuOK, TMPMgCl·LiCl, and LDA) reduce the N═N bond of the parent azobenzene (Y = H), aromatic H→Li permutation occurs with LTMP when a suitable director of lithiation (Y = OMe, CONEt2, F) is present in the benzene residue of the azo compound. The method allows direct access to new substituted azobenzenes.

Molecular iodine initiates hydroborations of alkenes with N-heterocyclic carbene boranes.

The hydroboration of alkenes of diverse structural types by assorted N-heterocyclic carbene boranes can be accomplished by addition of 5-10% diiodine. For example, reaction of 1,3-dimethylimidazol-2-ylidene borane (diMe-Imd-BH3) with 10% I2 followed by addition of 2,3-dimethyl-2-butene provided the corresponding thexyl NHC-borane (diMe-Imd-BH2thexyl) in 75% yield. This and related monohydroboration products are stable to chromatography and storage. The scope of the new reaction is described, and the mechanism is probed by (11)B NMR experiments.

Borenium ion catalyzed hydroboration of alkenes with N-heterocyclic carbene-boranes.

Treatment of alkenes such as 3-hexene, 3-octene, and 1-cyclohexyl-1-butene with the N-heterocyclic carbene (NHC)-derived borane 2 and catalytic HNTf(2) (Tf = trifluoromethanesulfonyl (CF(3)SO(2))) effects hydroboration at room temperature. With 3-hexene, surprisingly facile migration of the boron atom from C(3) of the hexyl group to C(2) was observed over a time scale of minutes to hours. Oxidative workup gave a mixture of alcohols containing 2-hexanol as the major product. A similar preference for the C(2) alcohol was observed after oxidative workup of the 3-octene and 1-cyclohexyl-1-butene hydroborations. NHC-borenium cations (or functional equivalents) are postulated as the species that accomplish the hydroborations, and the C(2) selective migrations are attributed to the four-center interconversion of borenium cations with cationic NHC-borane-olefin π-complexes.

Radical cyclization of α-bromo aluminum acetals onto alkenes and alkynes (radic[Al] process): a simple access to γ-lactols and 4-methylene-γ-lactols.

An efficient preparation of γ-lactols and methylene-γ-lactols is described. Highly acid-sensitive lactols are prepared in a concise manner by using a radical cyclization of aluminum acetals. The precursors for the radical reactions are readily prepared from allyl or propargyl alcohols and α-bromo acids. Functionalization of the resulting γ-lactols and methylene-γ-lactols can be achieved following isolation, leading to synthetically useful building blocks, such as 1,4-diols, 1,4-dienes, γ-lactones, and polysubstituted tetrahydrofurans.