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

Abstract

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)CH2OSiPh2 tBu [(R)- and (S)-21, El = Ge; (R)- and (S)-23, El = C], (R)- and (S)-p-FC6H4(H)El(CH2OAc)CH2OSiPh2 tBu [(R)- and (S)-22, El = Ge; (R)- and (S)-24, El = C], Ph(H)El(CH2OH)CH2OSiPh2 tBu [(R)- and (S)-25, El = Ge; (R)- and (S)-27, El = C], and (R)- and (S)-p-FC6H4(H)El(CH2OH)CH2OSiPh2 tBu [(R)- and (S)-26, El = Ge; (R)- and (S)-28, El = C] di...

Rhodium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic Dibenzosiloles by Enantioselective [2+2+2] Cycloaddition

“…Triynes having two identically substituted arylethynyl groups on the silicon atom (1 d and 1 e) are also suitable substrates for the reaction with alkyne 2 a to give 3 da and 3 ea with similar enantiomeric excesses (85-89 % ee; entries 4 and 5). [22] More functionalized dibenzosiloles 3 hg/3 hg' bearing polymerizable sites through the (sila-)Sonogashira coupling can also be prepared enantioselectively (96 % ee and 70 % ee, respectively) as shown in Eq. With regard to the internal alkyne, symmetrical alkynes, such as 2 a, 1,4-diacetoxy-2-butyne (2 b), and bis(4-methoxyphenyl)acetylene (2 c), as well as unsymmetrical alkynes, such as dimethyl 2-(2-butynyl)-2-methylmalonate (2 d), methyl tetrolate (2 e), and 1-phenyl-1-propyne (2 f), can be employed for the present catalysis to give 3 aa-3 ae and 3 df/3 df' in high yields (80-92 % yield) with up to 96 % ee (entries [8][9][10][11][12].…”

“…It is worth mentioning that the reactions of 1 a with unsymmetrical 2 d and 2 e proceed with high regioselectivity to give 3 ad (99:1; entry 10) and 3 ae (93:7; entry 11) respectively, [21] although the reaction of 1 d with 2 f gives a 70:30 mixture of regioisomers (entry 12). [22] More functionalized dibenzosiloles 3 hg/3 hg' bearing polymerizable sites through the (sila-)Sonogashira coupling can also be prepared enantioselectively (96 % ee and 70 % ee, respectively) as shown in Eq. (1) with moderate regioselectivity (76:24).…”

Organosilicon Biotechnology

“…It Fig. 1 The diastereoselective reduction of trimethylsilylalkyl acetoacetates by K. corticis [34] is particularly interesting that both the silicon and germanium analogs were reduced at a higher rate than their carbon counterpart, 3-methyl-3-phenyl-2-butanone [37]. 1 Both silicon and germanium afford, at least to some extent, an increase in the steric bulk due to larger Si-C and Ge-C bond lengths that are proximal to the acyl group which may be conducive to facilitating the reduction; the larger atoms may facilitate incorporation of the substrate into the enzymes' binding pocket.…”

“…Notable exceptions to this also come from R. Tacke and coworkers. For further reading on the subject of enzymatic transformations of organogermanes see Tacke et al [37,38]; and Wagner et al [39]. For organostannes see Therisod [40].…”

Syntheses, Stereochemistry, and Dynamic Behavior of Chiral Zwitterionic (Ammoniomethyl)bis[glycolato(2–)-O1,O2]silicates

“…Following the strategy described for the synthesis of (12), and (MeO) 3 SiCH 2 NMe 2 (13). Compounds 8 and 9 1Ϫ4, [2e,2g] compounds 5Ϫ9 were prepared according to were synthesized alternatively according to Scheme 2 and method a by reaction of the respective silanes 11Ϫ13 with two mol equivalents of glycolic acid and 2-methyllactic [a] Institut für Anorganische Chemie, Universität Würzburg acid, respectively (Scheme 1).…”