Premium
Reversal of Stereoselectivity in Lithiation of Ferrocenyl‐imidazolones: Epimeric Substrates lead to Planar Chiral Enantiomers
Author(s) -
Metallinos Costa,
John Joshni,
Nelson Jonathan,
Dudding Travis,
Belding Lee
Publication year - 2013
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201300021
Subject(s) - chemistry , stereoselectivity , stereocenter , stereochemistry , enantiomer , epimer , chirality (physics) , electrophile , chiral auxiliary , stereospecificity , enantioselective synthesis , organic chemistry , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
Diastereoselective induction of planar chirality in ferrocenes often employs chiral sulfur‐, carbon‐ or phosphorus‐based directing groups. The origin of stereoselectivity in these reactions may be classified as (a) cyclopentadiene (Cp) ring‐controlled or (b) base‐controlled. These two categories are represented by auxiliaries that typically have stereogenic centers α or γ to the ferrocene core, respectively. In this study, it is shown that (−)‐2‐ferrocenyl‐1 S ‐triethylsilyloxy‐7a S ‐hexahydropyrrolo[1,2‐ c ]imidazol‐3‐one, the anti ‐epimer of the previously reported syn ‐(1 R ,7a S ) substrate, induces lithiation of the pro‐ R p rather than the pro‐ S p Cp hydrogen in >95:5 dr , leading to enantiomers of the syn ‐derived planar chiral imidazolones upon electrophile quench and elimination. This outcome provides a practical way to prepare planar chiral enantiomers in this series without having to synthesize a more expensive D ‐proline‐derived starting material, since both the syn and anti starting materials are available from a common L ‐proline‐derived intermediate. The origin of stereoselectivity in lithiation of the syn and anti epimers, which have β,γ‐stereogenic centers, appears to be driven primarily by the conformational bias exerted by the β‐silyloxy moiety in each chiral auxiliary, which positions the urea carbonyl within the proximity of one of the two prochiral ortho Cp hydrogens. As such, stereoselectivity is likely Cp ring‐controlled for both compounds despite their lack of α‐ferrocenyl stereogenic centers. This conclusion is supported by the insensitivity of lithiation selectivity to the bulkiness of the base, comparisons of enantiomers, deuteration experiments, nOe difference studies, and computational modeling of the ground states and lithiation transition states for both substrates.