ENZYMATIC TRANSFORMATION AND LIQUID-CHROMATOGRAPHIC SEPARATION AS METHODS FOR THE PREPARATION OF THE (R)-ENANTIOMER AND (S)-ENANTIOMER OF THE CENTROCHIRAL HYDRIDO-GERMANES P-XC6H4(H)GE(CH2OAC)CH2OH (X = H, F)

The arylbis(hydroxymethyl)germanes Ph(H)Ge(CH2OH)(2) (5) and p-FC6H4(H )Ge(CH2OH)(2) (6) as well as the bis(acetoxymethyl)arylgermanes Ph(H)G e(CH2OAc)(2) (9) and P-FC6H4(H)Ge(CH2OAc)(2) (10) were synthesized, st arting from dichlorobis(chloromethyl)germane [Cl2Ge(CH2Cl)(2) --> Aryl (Cl)Ge(CH2Cl)(2) --> Aryl(AcO)Ge(CH2OAc)(2) --> Aryl(H)Ge(CHeOH)(2) -- > Aryl(H)Ge(CH2OAc)(2); Aryl = Ph, P-FC6H4] Reaction of the diols 5 an d 6 with Ac2O and NEt3 (molar ratio 1:1:1) yielded the (acetoxymethyl) aryl(hydroxymethyl)german rac-Ph(H)Ge(CH2OH)CH2OAc (rac-1) and rac-p-F C6H4(H)Ge(CH2OH)CH2OAc (rac-2), respectively. The (R)- and (S)-enantio mers of 1 and 2 were prepared on a preparative scale by enzymatic conv ersions. (R)-1 and (R)-2 were obtained by enantioselective transesteri fications of the prochiral diols 5 and 6, respectively, with ethyl ace tate (acyl donor) using porcine pancreas lipase (PPL, E.C.3.1.1.3) as the biocatalyst (reaction medium, ethylacetate). The corresponding ant ipodes (S)-1 and (S)-2 were prepared by PPL-catalyzed enantioselective hydrolyses of the prochiral diacetates 9 and 10, respectively [reacti on medium, Sorensen phosphate buffer (pH 7)/tetrahydrofuran (25:1, v/v )]. The yields and enantiomeric purities of the optically active germa nes 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 usi ng cellulose tribenzoate as the chiral stationary phase (yield 80%; en antiomeric purities 97% eel. For reasons of comparison, the (R)- and ( S)-enantiomers of Ph(H)C(CH2OH)CH2OAc (3) and p-FC6H4(H)C(CH2OH)CH2OAc (4) (carbon analogues of the germanes 1 and 2) were prepared using th e same preparative methods [PPL-catalyzed transesterifications of Ph(H )C(CH2OH)(2) (7) and p-FC6H4(H)C(CH2OH)(2) (8) with vinyl acetate and ethyl acetate, respectively (--> (R)-3, (R)-4); PPL-catalyzed hydrolys es of Ph(H)C(CH2OAc)(2) (11) and p-FC6H4(H)C(CH2OAc)(2) (12) (--> (S)- 3, (S)-4); chromatographic resolution of rac-p-FC6H4(H)C(CH2OH)CH2OAc (rac-4) (--> (R)-4, (S)-4)]. The preparative results were similar to t hose obtained for the germanium compounds. In contrast to the configur ationally stable antipodes of the carbon compounds 3 and 4, the (R)- a nd (S)-enantiomers of the corresponding germanium analogues 1 and 2 un dergo a slow racemization upon heating (neat compounds). The chiroptic al 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)- an d (S)-Ph(H)El(CH2OAc)CH(2)OSiPh(2)tBu [(R)- and (S)-21, El = Ge; (R)- and (S)-23, El = C], (R)- and (S)-p-FC6H4(H)El(CH2OAc)CH(2)OSiPh(2)tBu [(R)- and (S)-22, El = Ge; (R)- and (S)-24, El = C], Ph(H)El(CH2OH)CH (2)OSiPh(2)tBu [(R)- and (S)-25, El = Ge; (R)- and (S)-27, El = C], an d (R)- and (S)-p-FC6H4(H)El(CH2OH)CH(2)OSiPh(2)tBu [(R)- and (S)-26, E l = Ge; (R)- and (S)-28, El = C] display similar chiroptical propertie s when having the same absolute configuration. The antipodes of 21-24 were prepared by silylation of the corresponding (R)- and (S)-enantiom ers of 1-4 with Ph(2)tBuSiCl; the antipodes of 25-28 were obtained by transesterification of the (R)- and (S)-enantiomers of 21-24 with meth anol tall reactions with retention of absolute configuration).