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)Ge(CH2OAc)2 (9) and p-FC6H4(H)Ge(CH2OAc)2 (10) were synthesized, starting from dichlorobis(chloromethyl)germane [Cl2Ge(CH2Cl)2 → Aryl(Cl)Ge(CH2Cl)2 → Aryl(AcO)Ge(CH2OAc)2 → Aryl(H)Ge(CH2OH)2 → Aryl(H)Ge(CH2OAc)2; Aryl = Ph, p-FC6H4]. Reaction of the diols 5 and 6 with Ac2O and NEt3 (molar ratio 1:1:1) yielded the (acetoxymethyl)aryl(hydroxymethyl)germanes rac-Ph(H)Ge(CH2OH)CH2OAc (rac-1) and rac-p-FC6H4(H)Ge(CH2OH)CH2OAc (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(CH2OH)CH2OAc (3) and p-FC6H4(H)C(CH2OH)CH2OAc (4) (carbon analogues of the germanes 1 and 2) were prepared using the 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 hydrolyses 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 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(CH2OAc)CH2OSiPh2tBu [(R)- and (S)-21, El = Ge; (R)- and (S)-23, El = C], (R)- and (S)-p-FC6H4(H)El(CH2OAc)CH2OSiPh2tBu [(R)- and (S)-22, El = Ge; (R)- and (S)-24, El = C], Ph(H)El(CH2OH)CH2OSiPh2tBu [(R)- and (S)-25, El = Ge; (R)- and (S)-27, El = C], and (R)- and (S)-p-FC6H4(H)El(CH2OH)CH2OSiPh2tBu [(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 Ph2tBuSiCl; 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).
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Jan 7, 2017
Yusuke Murakami + 2
