Organolithiums in Enantioselective Additions to π* and σ* Carbon-Oxygen Electrophiles

Abstract

Mediated by chiral, non-racemic ligands, organolithiums add enantioselectively to C=O functions of carbonyl compounds (aldehydes and ketones) or cleave enantioselectively C-O units in strained ethers (epoxides and oxetanes) as well as in acetals. The achievement of high enantioselectivities is desirable and hence factors controlling these enantioselectivities are the subject of intensive research. Beneficial external influences on enantioselectivity are low temperatures, suitable solvents (e.g. dimethoxymethane, dimethyl ether) and the exclusion of salt impurities. Organolithium reagents and ligands lithiated in situ form mixed anionic aggregates, some of which can be isolated and even structurally studied. The improved understanding of the nature of such chiral organolithium aggregates provides the way to a more rational design of new enantioselective organolithium reagents.

Formation of C–C Bonds via Iridium-Catalyzed Hydrogenation and Transfer Hydrogenation

“…In addition to late transition metals (Cu, Rh) (see footnote 14) [117, 118], early transition metal catalysts (Ti, Zr, Hf) (For enantioselective zirconium, titanium and hafnium catalyzed addition of organozinc reagents to imines, see: [119–124]) are found to promote the highly enantioselective addition of organozinc reagents to imines. The enantioselective addition of organolithium reagents to imines promoted or catalyzed by chiral chelating agents also has been described (For reviews encompassing catalytic enantioselective addition of organolithium reagents to carbonyl compounds and imines, see: [125–132]). Finally, under the conditions of rhodium catalysis, organotin, organotitanium, and organoboron reagents participate in catalytic asymmetric imine addition (For enantioselective rhodium catalyzed addition of organometallic reagents to imines, see: Organotin reagents [133–134], Organotitanium reagents [135] and Organoboron reagents [136]).…”

Aggregation and Solvation of Chiral N,P‐Amide Ligands in Coordinating Solvents: A Computational and NMR Spectroscopic Study

“…For this reason, we can dispense with calculation of reference compounds and simply compare calculated absolute shieldings directly to observed shifts. The relationship between sp 2 -and sp 3 -carbon values of theoretical shieldings and experimental chemical shifts of the most stable complexes according to the aggregation-solvation diagram were investigated. The five carbon atoms included in these calculations to make the comparison are shown in Figure 4.…”

“…Lithium-organic compounds are used for a wide range of purposes in organic chemistry, as nucleophiles in carbonÀcarbon bond-formation reactions, but also as bases. [1][2][3][4] Asymmetric versions can be obtained by the introduction of chiral elements into the lithium coordination sphere. [5,6] Particularly appealing are lithium amides that are derived from chiral secondary amines, because of the strong coordination of the anionic nitrogen to lithium, and the wide range of available chiral amines.…”

“…[7] Addition of chelating groups to the amide framework allows for structurally rigid chiral ligands that have been shown to be efficient in applications ranging from desymmetrisation by basic epoxide deprotonation [8][9][10][11] to asymmetric alkyl addition to aldehydes. [3,4,[12][13][14][15][16][17] Earlier work has demonstrated that amino acids can provide libraries of lithium ligands with interesting properties in few synthetic steps. [18] Steric properties close to lithium can be varied by the starting amino acid and amine substituent (R and R'; Scheme 1), and also by the nature of the pendant chelating group Y.…”

Pincer Complexes of Lithium, Sodium, Magnesium and Related Metals: A Discussion of Solution and Solid-State Aggregated Structure and Reactivity

“…Obviously, these mixtures can become different complexes if good donor ligands/solvents are present (cf. the use of (À)-sparteine [lupinidine] in enantioselective reactions involving RLi) [67][68][69]. One presumes that the isomeric forms must have very similar or identical reactivity patterns; otherwise, complex product mixtures would predominate the use of such reagents.…”