Enantioselective Lithiation and Substitution of (E)-CinnamylN,N-Diisopropylcarbamate through Use of (−)-Sparteine Complexes

Abstract

The title reaction leads to diastereomeric lithium carbanion pairs that are configurationally unstable and equilibrate even at temperatures below –50 °C. The initially formed epimer (1S)‐epi‐10 is rapidly converted to the thermodynamically more stable (1R)‐10 (in toluene solution). Carboxylation, acylation with acid chlorides, stannylation, and silylation take place at the α‐position with stereoinversion (79‐86% ee). Methylating agents attack the γ‐position; here, the stereochemical course depends on the leaving group, anti‐SE′ for the iodide (50% ee) and syn‐SE′ (48% ee) for the tosylate.

Configurationally Labile Enantioenriched Lithiated 3-Arylprop-2-enyl Carbamates: Joint Experimental and Quantum Chemical Investigations on the Equilibrium of Epimers

“…After evaporation of the solvent under vacuum, purification of the residue yielded 3a (77 mg, 0.23 mmol, 80%) as a white solid: mp 65−67 °C (Et 2 O); R f 0.38 (Et 2 O/PE = 1:4); [α] 20 D −11.4 ( c 1.08, CH 2 Cl 2 , er = 96:4); 1 H NMR (400 MHz, CDCl 3 ) δ/ppm 0.06 (s, 9 H), 1.20 (s, 12 H), 3.81, 4.02 (2 br s, 2 H), 5.24 (dd, J = 6.1, 1.1 Hz, 1 H), 6.21 (dd, J = 15.9, 6.1 Hz, 1 H), 6.33 (dd, J = 15.9, 1.1 Hz, 1 H), 7.13−7.15 (m, 1 H), 7.20−7.25 (m, 4 H); 13 C NMR (75 MHz, CDCl 3 ) δ/ppm −3.49, 20.6, 21.4, 45.1, 46.4, 70.5, 126.1, 126.8, 128.2, 128.4, 137.5, 155.6. Chiral HPLC: ChiraGrom-2 250 × 2 mm; i -PrOH/ n -hexane =1:600; 0.3 mL min −1 ; t R = 9 min (main enantiomer), t R = 12 min; the spectroscopic data are in agreement with the literature …”

“…The substitution occurred exclusively in the α-position, and the enantioenriched products ( 3a − e ) (er = 94:6−97:3) were obtained in moderate to good yield (50−88%). The configuration of the newly formed stereogenic centers was determined by comparison of the optical rotation with these of known examples, and considering an invertive substitution with tin and silyl electrophiles. , …”

Synthesis of Enantiomerically Enriched Allenes by (−)-Sparteine-Mediated Lithiation of Alkynyl Carbamates

“…It is reasonable to assume that the lithium−titanium exchange in the (−)-sparteine complexes 5 proceeds with inversion (as has been found for related allyllithium compounds 10b ) and the crystallizing epimer 5a has the ( S )-configuration. The formation of the carboxylation product ( S )- 6a as the major product from 5a is in accordance with this hypothesis, since we regularly found inversion in these reactions 3 Mechanism of the Asymmetric Deprotonation and Substitution of 2-Alkynyl Carbamates a a Only the major stereoisomers are shown. …”

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

“…A form of kinetic resolution occurs in which the minor organolithium is rapidly converted to product, followed slowly by the major organolithium [ 28 ]. Hoppe observed a related effect in the alkylations of cinnamyllithiums [ 29 ].…”