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A Synthesis Detour to Planar‐Diastereoisomeric Ferrocene Derivatives around an Unexpected Rearrangement of ortho ‐Lithiated Kagan 's Template [ S ( S )] ‐ ( p ‐Tolylsulfinyl)ferrocene
Author(s) -
Weber Immo,
Heinemann Frank W.,
Zenneck Ulrich
Publication year - 2007
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.200790082
Subject(s) - chemistry , lithium diisopropylamide , ferrocene , electrophile , diastereomer , quenching (fluorescence) , medicinal chemistry , lithium (medication) , stereochemistry , organic chemistry , catalysis , electrochemistry , deprotonation , ion , medicine , physics , fluorescence , endocrinology , electrode , quantum mechanics
Abstract Usually, ortho lithiation of Kagan 's template 1 and quenching with electrophiles leads highly diastereoselectively to planar‐chiral 1,2‐disubstituted ferrocenes. Surprisingly, lithiation of 1 with lithium diisopropylamide (LDA) followed by addition of paraformaldehyde afforded regioisomer (+)‐{[ S ( S )] ‐ [4‐(2‐hydroxyethyl)phenyl]sulfinyl}ferrocene ( 2 ), which was converted to (+)‐{[ S ( S )] ‐ {4‐{2‐[(methylsulfonyl)oxy]ethyl}phenyl}sulfinyl}ferrocene ( 3 ) ( Scheme 1 ). The desired diastereoisomer ( l )‐1‐(hydroxymethyl)‐2‐( p ‐tolylsulfinyl)ferrocene ( 5 ) in turn could also be obtained by ortho lithiation of 1 with LDA but by quenching with DMF to yield aldehyde 4 first, which then was reduced with NaBH 4 to 5 . Finally, target compound ( l )‐1‐[(dimethylamino)methyl]‐2‐( p ‐tolylsulfinyl)ferrocene ( 6 ) was obtained by substitution of the OH group of 5 under mild conditions or directly by ortho lithiation of 1 with lithio‐2,4,6‐triisopropylbenzene (=2,4,6‐triisopropylphenyl)lithium; LTP) followed by quenching with N , N ‐dimethylmethyleneiminium chloride. At low temperatures, reaction of 1 with LDA leads, via the preferred diastereoisomeric transition state ‘ exo ’‐ 7 and under extrusion of a (diisopropylamine)lithium complex of type 8 , in a highly selective manner, to diastereoisomeric ortho ‐lithiated chelate ( l )‐ 9 ( Scheme 2 ). The reaction of 1 to 2 is explained by a rearrangement of ( l )‐ 9 to {[ S ( S )] [4‐(lithiomethyl)phenyl]sulfinyl}ferrocene 10 , which is acid‐catalyzed by coordinated diisopropylamine in complexes of type 8 . This rearrangement is not observed if LTP is used as base or, in case LDA is applied, if the electrophile is sufficiently reactive at low temperatures.