Diastereoselective deprotonative metalation of chiral ferrocene derived acetals and esters using mixed lithium–cadmium and lithium–zinc combinations

• Published in: Tetrahedron Vol. 70; no. 12; pp. 2102 - 2117
• Main Authors: Dayaker, Gandrath, Sreeshailam, Aare, Ramana, D. Venkata, Chevallier, Floris, Roisnel, Thierry, Komagawa, Shinsuke, Takita, Ryo, Uchiyama, Masanobu, Krishna, Palakodety Radha, Mongin, Florence
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 25.03.2014; Elsevier
• Subjects: Acetals; Asymmetry; Bimetals; Cadmium; Carbohydrates; Carboxylates; Chemical Sciences; Chemistry; Chemistry, Organic; Deproto-metalation; Derivatives; Esters; Ferrocene; Ferrocenes; Inorganic chemistry; Lithium; Physical Sciences; Science & Technology; Tetrahedrons; Zinc; Carbohydrates; Cadmium; Lithium; Deproto-metalation; Zinc; Ferrocene; ASYMMETRIC-SYNTHESIS; SINGLE CONCEPT; COMPUTED CH ACIDITY; PLANAR CHIRALITY; AGGREGATE MAA; TERTIARY AMIDE; MEDIATED ZINCATION; CHEMISTRY; LITHIATION; EFFICIENT
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2014.02.010

In situ bimetal combinations, and notably those prepared from MCl2(TMEDA) (M=Zn, Cd; TMEDA=N,N,N′,N′-tetramethylethylenediamine) and Li(TMP) (3 or 4 equiv, TMP=2,2,6,6-tetramethylpiperidino), were screened for their ability to diastereoselectively deprotonate ferrocenes bearing a chiral group. The ferrocene carboxylate generated from diacetone-d-glucose afforded the corresponding 2-iodo derivative in 74% yield with 90% de (SP diastereoisomer) using the base generated from CdCl2 and Li(TMP) (3 equiv), and in 85% yield with 91% de (SP diastereoisomer) through a double asymmetric induction using a chiral lithium–zinc base generated from ZnCl2·TMEDA and lithium (R)-bis(1-phenylethyl)amide (4 equiv). In contrast, using a combination prepared from ZnCl2 and Li(TMP) (4 equiv) with the ferrocene carboxylate obtained from 6-(tert-butoxycarbonylamino)-6-deoxy-3-O-methyl-1,2-O-isopropylidene-α-d-glucofuranose led to the RP-iodo derivative in 57% yield after separation. Suzuki coupling was performed satisfactorily on the isolated SP and RP diastereoisomer iodoesters. [Display omitted]