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Preparation and Characterization of New C 2 ‐ and C 1 ‐Symmetric Nitrogen, Oxygen, Phosphorous, and Sulfur Derivatives and Analogs of TADDOL. Part I
Author(s) -
Pichota Arkadius,
Gramlich Volker,
Beck Albert K.,
Seebach Dieter
Publication year - 2012
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200146
Subject(s) - chemistry , sulfanyl , catalysis , reagent , enantioselective synthesis , alkoxy group , medicinal chemistry , organic chemistry , alkyl
The chloro alcohols 4 – 6 derived from TADDOLs (= α , α , α′ , α′ ‐tetraaryl‐1,3‐dioxolan‐4,5‐dimethanols) are used to prepare corresponding sulfanyl alcohols, ethers, and amines ( Scheme 1 and Table 1 ). The dithiol analog of TADDOL and derivatives thereof, 45 – 49 , were also synthesized. The crystal structures of 16 representatives of this series of compounds are reported ( Figs. 1 – 3 and Scheme 2 ). The thiols were employed in Cu‐catalyzed enantioselective conjugate additions of Grignard reagents to cyclic enones, with cycloheptenone giving the best results (er up to 94 : 6). The enantioselectivity reverses from Si ‐addition with the sulfanyl alcohol to Re ‐addition with the alkoxy or dimethylamino thiols ( Table 4 ). Cu I ‐Thiolates, 50 – 53 , could be isolated in up to 84% yield ( Scheme 2 ) and were shown to have tetranuclear structures in the gas phase (by ESI‐MS), in solution (CH 2 Cl 2 , THF; by vapor‐pressure osmometry and by NMR pulsed‐gradient diffusion measurements; Table 5 ), and in the solid state (X‐ray crystal structures in Scheme 2 ). The Cu complex 50 of the sulfanyl alcohol is stable in air and in the presence of weak aqueous acid, and it is a highly active catalyst (0.5 mol‐%) for the 1,4‐additions, leading to the same enantio‐ and regioselectivities observed with the in situ generated catalyst (6.5 mol‐%; Scheme 3 ). Since the reaction mixtures contain additional metal salts (MgX 2 , LiX) it is not possible at this stage, to propose a mechanistic model for the conjugate additions.