Enzymatic Transformation and Liquid-Chromatographic Separation as Methods for the Preparation of the (<i>R</i>)- and (<i>S</i>)-Enantiomers of the Centrochiral Hydridogermanes<i>p</i>-XC₆H₄(H)Ge(CH₂OAc)CH₂OH (X = H, F)

Abstract

The arylbis(hydroxymethyl)germanes Ph(H)Ge(CH 2 OH) 2 ( 5 ) and p -FC 6 H 4 (H)Ge(CH 2 OH) 2 ( 6 ) as well as the bis(acetoxymethyl)arylgermanes Ph(H)Ge(CH 2 OAc) 2 ( 9 ) and p -FC 6 H 4 (H)Ge(CH 2 OAc) 2 ( 10 ) were synthesized, starting from dichlorobis(chloromethyl)germane [Cl 2 Ge(CH 2 Cl) 2 → Aryl(Cl)Ge(CH 2 Cl) 2 → Aryl(AcO)Ge(CH 2 OAc) 2 → Aryl(H)Ge(CH 2 OH) 2 → Aryl(H)Ge(CH 2 OAc) 2; Aryl = Ph, p -FC 6 H 4 ]. Reaction of the diols 5 and 6 with Ac 2 O and NEt 3 (molar ratio 1:1:1) yielded the (acetoxymethyl)aryl(hydroxymethyl)germanes rac -Ph(H)Ge(CH 2 OH)CH 2 OAc ( rac - 1 ) and rac - p -FC 6 H 4 (H)Ge(CH 2 OH)CH 2 OAc ( rac - 2 ), respectively. The ( R )- and ( S )-enantiomers of 1 and 2 were prepared on a preparative scale by enzymatic conversions. ( R )- 1 and ( R )- 2 were obtained by enantioselective transesterifications of the prochiral diols 5 and 6, respectively, with ethyl acetate (acyl donor) using porcine pancreas lipase (PPL, E.C.3.1.1.3) as the biocatalyst (reaction medium, ethyl acetate). The corresponding antipodes ( S )- 1 and ( S )- 2 were prepared by PPL-catalyzed enantioselective hydrolyses of the prochiral diacetates 9 and 10, respectively [reaction medium, Sörensen phosphate buffer (pH 7)/tetrahydrofuran (25:1, v/v)]. The yields and enantiomeric purities of the optically active germanes were as follows: ( R )- 1, 76%, 93% ee; ( S )- 1, 48%, 84% ee; ( R )- 2, 77%, 86/87% ee; ( S )- 2, 62%, 94% ee. Alternatively, ( R )- 2 and ( S )- 2 were obtained by preparative liquid-chromatographic resolution of rac - 2 using cellulose tribenzoate as the chiral stationary phase (yield 80%; enantiomeric purities 97% ee). For reasons of comparison, the ( R )- and ( S )-enantiomers of Ph(H)C(CH 2 OH)CH 2 OAc ( 3 ) and p -FC 6 H 4 (H)C(CH 2 OH)CH 2 OAc ( 4 ) (carbon analogues of the germanes 1 and 2 ) were prepared using the same preparative methods [PPL-catalyzed transesterifications of Ph(H)C(CH 2 OH) 2 ( 7 ) and p -FC 6 H 4 (H)C(CH 2 OH) 2 ( 8 ) with vinyl acetate and ethyl acetate, respectively (→ ( R )- 3, ( R )- 4 ); PPL-catalyzed hydrolyses of Ph(H)C(CH 2 OAc) 2 ( 11 ) and p -FC 6 H 4 (H)C(CH 2 OAc) 2 ( 12 ) (→ ( S )- 3, ( S )- 4 ); chromatographic resolution of rac - p -FC 6 H 4 (H)C(CH 2 OH)CH 2 OAc ( rac - 4 ) (→ ( R )- 4, ( S )- 4 )]. The preparative results were similar to those obtained for the germanium compounds. In contrast to the configurationally stable antipodes of the carbon compounds 3 and 4, the ( R )- and ( S )-enantiomers of the corresponding germanium analogues 1 and 2 undergo a slow racemization upon heating (neat compounds). The chiroptical properties of the Ge/C analogues ( R )- 1 /( R )- 3, ( S )- 1 /( S )- 3, ( R )- 2 /( R )- 4, and ( S )- 2 /( S )- 4 (dissolved in acetone) differ significantly from one another (opposite signs of optical rotation at various wavelengths). In contrast, the respective optically active Ge/C analogues ( R )- and ( S )-Ph(H)El(CH 2 OAc)CH 2 OSiPh 2 t Bu [( R )- and ( S )- 21, El = Ge; ( R )- and ( S )- 23, El = C], ( R )- and ( S )- p -FC 6 H 4 (H)El(CH 2 OAc)CH 2 OSiPh 2 t Bu [( R )- and ( S )- 22, El = Ge; ( R )- and ( S )- 24, El = C], Ph(H)El(CH 2 OH)CH 2 OSiPh 2 t Bu [( R )- and ( S )- 25, El = Ge; ( R )- and ( S )- 27, El = C], and ( R )- and ( S )- p -FC 6 H 4 (H)El(CH 2 OH)CH 2 OSiPh 2 t Bu [( R )- and ( S )- 26, El = Ge; ( R )- and ( S )- 28, El = C] display similar chiroptical properties when having the same absolute configuration. The antipodes of 21 − 24 were prepared by silylation of the corresponding ( R )- and ( S )-enantiomers of 1 − 4 with Ph 2 t BuSiCl; the antipodes of 25 − 28 were obtained by transesterification of the ( R )- and ( S )-enantiomers of 21 − 24 with methanol (all reactions with retention of absolute configuration).