Spontaneous Resolution and Carbonation of Chiral Benzyllithium Complexes

Abstract

In search for new examples of absolute asymmetric synthesis (AAS), chiral α‐substituted benzyllithium complexes have been prepared. While [Li(phet)(pmdta)] (1) (phet = 1‐phenylethyl, pmdta = N,N,N′,N″,N″‐pentamethyldiethylenetriamine) affords only racemic crystals, a promising candidate for AAS was indeed found: [Li(phet)(tmpda)], α‐2, (tmpda = N,N,N′,N′‐tetramethylpropylenediamine) crystallises as a conglomerate. Although concomitant polymorphism was not observed, a racemic phase (β‐2) could also be isolated. Chiral crystals of α‐2 gave 2‐phenylpropionic acid in high yield on reaction with gaseous CO2, but the bulk product was racemic. It is unclear whether the lack of selectivity originates during crystallisation or carbonation. In order to investigate this, similar complexes displaying Si or S atoms in the α‐position were prepared and structurally characterized: [Li(tmsb)(tmpda)] (tmsb = 1‐trimetylsilylbenzyl) (3), [Li{C(CH3)(Ph)(SPh)}(pmdta)] (4), [Li{C(CH3)(Ph)(SPh)}(tmeda)] (5), and [Li(tmeda)2][C(CH3)(Ph)(SPh)] (6). The introduction of heavy atoms should allow determination of absolute configuration and enantiopurity, but so far only racemic crystals have been obtained.

Solid state and solution studies of lithium tris(n-butyl)magnesiates stabilised by Lewis donors

“…1). 32 Li-N distances of 1, [2.085(4) to 2.092(4) Å], are similar to those found for other lithium compounds stabilised by chelating TMPDA. The former rings are fused to the latter at different Mg atoms.…”

A monomeric (trimethylsilyl)methyl lithium complex: synthesis, structure, decomposition and preliminary reactivity studies

“…For these reasons, synthetic organometallic chemists have devoted decades of effort to synthesising the LiR monomers and studying their structures and reactivity. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] The most successful strategy to break the LiR aggregates and isolate LiR monomers is to employ neutral multidentate amines, 4 which coordinate to the Li and kinetically stabilise the LiR monomers. Since the 1980s, this multidentate amine strategy has been successfully implemented by several groups to isolate a series of [Li(R)(L)] monomers (L = multi-amine ligands; R = CH 2 SiMe 3 , 5,6 CH(SiMe 3 ) 2 , 7,8 t Bu, 9,10 s Bu, 8 i Pr, 11 benzyl [12][13][14][15][16][17] ).…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18] The most successful strategy to break the LiR aggregates and isolate LiR monomers is to employ neutral multidentate amines, 4 which coordinate to the Li and kinetically stabilise the LiR monomers. Since the 1980s, this multidentate amine strategy has been successfully implemented by several groups to isolate a series of [Li(R)(L)] monomers (L = multi-amine ligands; R = CH 2 SiMe 3 , 5,6 CH(SiMe 3 ) 2 , 7,8 t Bu, 9,10 s Bu, 8 i Pr, 11 benzyl [12][13][14][15][16][17] ). Recently, we reported the first methyllithium monomer [Li(CH 3 )(DETAN)], enabled by a bespoke hexadentate ligand [{Et 2 NCH 2 CH 2 N(CH 2 CH 2 )} 3 ], namely N,N′,N″tris-(2-N-diethylaminoEthyl)-1,4,7-triAza-cycloNonane (DETAN).…”

Absolute Asymmetric Synthesis of Enantiopure Organozinc Reagents, Followed by Highly Enantioselective Chlorination

“…When such a reagent reacts with an electrophile, the chirogenic center in the organometallic reagent may remain intact, thus eliminating the need to transform helical chirality to central chirality. Our first attempts involved substituted benzyllithium complexes [19] and sec-butylzinc complexes. [32] To overcome difficulties encountered in handling extremely air-sensitive solid organolithium reagents, and the low rate of enantiomerization of dialkylzinc reagents, we turned to diindenylzinc complexes.…”

“…The creation of optical activity during a crystallization is referred to as total spontaneous resolution or crystallization‐induced asymmetric transformation15 and may be regarded as a form of absolute asymmetric synthesis. We have recently reported total spontaneous resolution of a number of different compounds, for example, organometallic reagents,16–19 an aluminium phenoxide complex,20 a coordination network,21 a conformationally chiral sulfide,22 an octanuclear organozinc complex,23 a helical coordination polymer,24 and several coordination compounds for example, five‐,25 seven‐26 and nine‐coordinate complexes 27. The stereochemical lability, which is required for total spontaneous resolution to occur, means that the optically active product will racemize on dissolution.…”