Parallel or classical kinetic resolution of a planar chiral ferrocenylketone through asymmetric reductions

Racemic 1-acetyl-2-methoxymethylferrocene, (±)-1 was subjected to asymmetric reduction with two different methodologies and complementary results were obtained. When the reduction of (±)-1 was carried out in the presence of CBS-oxazaborolidine catalyst and BH3·Me2S as the hydrogen source, both enantiomers of the substrate were converted with comparable reaction rates and selectivities. The corresponding diastereoisomeric ferrocenylalcohols 3a and 3b were obtained in a 1:1 ratio and >90% enantiomeric excess; this reaction profile being related with a parallel kinetic resolution with high ds1 and ds2 diastereofacial selectivities. On the contrary, the transfer hydrogenation of (±)-1 with HCOOH/triethylamine in the presence of (R,R)-Noyori’s catalyst proceeded via classical kinetic resolution, so that the formed (−)-3b or unreacted (+)-1 could be obtained in highly enantiopure form before or beyond 50% of the substrate conversion, respectively. Alcohol 3b with an (1Rp,S)- or (1Sp,R)-configuration is not easily accessible by the diastereoselective metallation/electrophilic quenching sequence routinely applied in the synthesis of planar chiral ferrocenes. As a result, the described procedures provide a valuable access to this useful starting material for the synthesis of homochiral related derivatives.

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(1Rp,S)-1-Acetoxyethyl-2-methoxymethylferroceneC16H20FeO3Ee = 93.8% (by chiral HPLC)[α]D25 = +21.8 (c 0.52, CHCl3)Source of chirality: asymmetric reduction of 1-acetyl-2-methoxy-methylferroceneAbsolute configuration: (1Rp,S)

(1Sp,S)-1-Acetoxyethyl-2-methoxymethylferroceneC16H20FeO3Ee = 90.4% (by chiral HPLC of the corresponding alcohol)[α]D25 = +77.3 (c 0.60, CHCl3)Source of chirality: asymmetric reduction of 1-acetyl-2-methoxy-methylferroceneAbsolute configuration: (1Sp,S)

(1Sp,S)-1-Hydroxyethyl-2-methoxymethylferroceneC14H18FeO2Ee = 90.4% (by chiral HPLC of the corresponding acetate)[α]D25 = −58.3 (c 0.18, CHCl3)Source of chirality: asymmetric reduction of 1-acetyl-2-methoxy-methylferroceneAbsolute configuration: (1Sp,S)

(1Rp,S)-1-Hydroxyethyl-2-methoxymethylferroceneC14H18FeO2Ee = 93.8% (by chiral HPLC)[α]D25 = +62.3 (c 0.52, CHCl3)Source of chirality: asymmetric reduction of 1-acetyl-2-methoxy-methylferroceneAbsolute configuration: (1Rp,S)

(1Sp)-1-Acetyl-2-methoxymethylferroceneC14H16FeO2Ee = 90.4% (by chiral HPLC)[α]D25 = +387.1 (c 0.41, CHCl3)Source of chirality: oxidation of the corresponding chiral alcoholAbsolute configuration: (1Sp)

(1Rp,S)-N,N-Dimethyl-1-[2-(hydroxymethyl)ferrocenyl]ethylamineC15H21FeOEe = 93.8%[α]D25 = −20.6 (c 0.25, EtOH)Source of chirality: enantiopure (1Rp,S)-1-acetoxyethyl-2-methoxymethylferroceneAbsolute configuration: (1Rp,S)

(1Sp,S)-1-Methoxyethyl-2-methoxymethylferroceneC15H20FeO2Ee = 90.4% (by chiral HPLC)[α]D25 = +27.6 (c 0.21, CHCl3)Source of chirality: asymmetric reduction of 1-acetyl-2-methoxy-methylferroceneAbsolute configuration: (1Sp,S)

(1Rp,S)-1-Methoxyethyl-2-methoxymethylferroceneC15H20FeO2Ee = 93.8% (by chiral HPLC of the corresponding alcohol)[α]D25 = −12.3 (c 0.49, CHCl3)Source of chirality: asymmetric reduction of 1-acetyl-2-methoxy-methylferroceneAbsolute configuration: (1Rp,S)