Enzymatic transformation and liquid-chromatographic separation as methods for the preparation of the (R)- and (S)-enantiomers of the centrochiral hydrido-germanes p-XC6H4(H)Ge(CH2OAc)CH2OH (X = H, F)

Article abstract of DOI:10.1021/om971025i

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(CH ₂Cl)₂→Aryl(AcO)Ge(CH₂OAc) ₂→Aryl(H)Ge(CH₂-OH) 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 racPh(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, So?rensen phosphate buffer (pH 7)/tetrahydrofuran (25:1, v/v)]. The yields and enantiomeric purities of the optically active germanes were as follows: (R)-1, 76percent, 93percent ee; (S)-1, 48percent, 84percent ee; (R)-2, 77percent, 86/87percent ee; (S)-2, 62percent, 94percent 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 80percent; enantiomeric purities 97percent ee). For reasons of comparison, the (R)- and (S)-enantiomers of Ph(H)C(CH₂OH)CH₂OAc (3) and p-FC₆H₄(H)C(CH₂OH)CH₂-OAc (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)CH ₂OSiPh₂tBu [(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)CH₂OSiPh ₂tBu [(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).

Full text of DOI:10.1021/om971025i

Organometallics 1998, 17, 1687-1699
1687
En zym a tic Tr a n sfor m a tion a n d Liqu id -Ch r om a togr a p h ic
Sep a r a tion a s Meth od s for th e P r ep a r a tion of th e (R)-
a n d (S)-En a n tiom er s of th e Cen tr och ir a l Hyd r id o-
ger m a n es p-XC6H4(H)Ge(CH2OAc)CH2OH (X ) H, F )
Reinhold Tacke,*,† Ulrike Kosub,† Stephan A. Wagner,† Ru¨diger Bertermann,†
Sigrid Schwarz,† Stefan Merget,‡ and Kurt Gu¨nther‡
Institut fu¨r Anorganische Chemie, Universita¨t Wu¨rzburg, Am Hubland,
D-97074 Wu¨rzburg, Germany, and Zentrale Forschungseinrichtungen der Degussa AG,
Rodenbacher Chaussee 4, D-63457 Hanau-Wolfgang, Germany
Received November 20, 1997
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 f Aryl(Cl)Ge(CH2Cl)2 f Aryl(AcO)Ge(CH2OAc)2 f Aryl(H)Ge(CH2-
OH)2 f 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), respec-
tively. 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, So¨rensen
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)CH2-
OAc (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 (f (R)-3, (R)-
4); PPL-catalyzed hydrolyses of Ph(H)C(CH2OAc)2 (11) and p-FC6H4(H)C(CH2OAc)2 (12)
(f (S)-3, (S)-4); chromatographic resolution of rac-p-FC6H4(H)C(CH2OH)CH2OAc (rac-4)
(f (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 wave-
lengths). 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).
* To whom correspondence should be addressed.
† Universita¨t Wu¨rzburg.
‡ Degussa AG (chromatographic studies).
S0276-7333(97)01025-X CCC: $15.00 © 1998 American Chemical Society
Publication on Web 03/31/1998

1688 Organometallics, Vol. 17, No. 9, 1998
Tacke et al.
In tr od u ction
tion of the optically active compounds obtained by the
aforementioned method. Recently, biotransformation
has also been demonstrated to be a useful preparative
method for the synthesis of optically active centrochiral
germanes.4l,n
Here we report on the synthesis of the (R)- and (S)-
enantiomers of the centrochiral hydridogermanes 1 and
2 using enantioselective enzymatic transformations. In
In contrast to the extensive research activities in the
field of centrochiral optically active silicon compounds
of the formula type R1R2SiR3R4,1-3 the chemistry of
related optically active germanium compounds is rather
unexplored.4 Very recently, it has been demonstrated
by pharmacological studies that biological systems can
discriminate between enantiomeric germanes.4m
The methods used for the preparation of the (R)- and
(S)-enantiomers of centrochiral germanes of the formula
type R1R2GeR3R4 are mainly based on (i) classical
resolution of the respective racemic mixtures via frac-
tional crystallization of appropriate diastereomeric de-
rivatives and (ii) stereoselective chemical transforma-
addition, the preparation of (R)-2 and (S)-2 by liquid-
chromatographic resolution of rac-2 is reported. For
reasons of comparison, the corresponding carbon ana-
logues (R)-3, (S)-3, (R)-4, and (S)-4 were also prepared
using the same methods. The main goal of the studies
presented here was the development of efficient syn-
thetic and chromatographic methods for the preparation
of centrochiral hydridogermanes with high enantiomeric
purity. The investigations concerning the enzymatic
conversions were carried out with a special emphasis
on the aspect “Ge/C bioisosterism”.
(1) Reviews on optically active silicon compounds of the formula type
R1R2SiR3R4: (a) Corriu, R. J . P.; Gue´rin, C. Adv. Organomet. Chem.
1982, 20, 265-312. (b) Corriu, R. J . P.; Gue´rin, C.; Moreau, J . J . E.
Top. Stereochem. 1984, 15, 43-198.
(2) Review dealing with the topic “chirality in bioorganosilicon
chemistry”: Tacke, R.; Wagner, S. A. In Organosilicon Chemistry;
Rappoport, Z., Apeloig, Y., Eds.; Wiley & Sons: Chichester, U.K.; Vol.
2, in press.
(3) Recent publications dealing with optically active silicon com-
pounds of the formula type R1R2SiR3R4: (a) Sheldrick, W. S.; Linoh,
H.; Tacke, R.; Lambrecht, G.; Moser, U.; Mutschler, E. J . Chem. Soc.,
Dalton Trans. 1985, 1743-1746. (b) Terunuma, D.; Kato, M.; Kamai,
M.; Uchida, H.; Ueno, S.; Nohira, H. Bull. Chem. Soc. J pn. 1986, 59,
3581-3587. (c) Tacke, R.; Becker, B. Main Group Met. Chem. 1987,
10, 169-197. (d) Tacke, R.; Linoh, H.; Ernst, L.; Moser, U.; Mutschler,
E.; Sarge, S.; Cammenga, H. K.; Lambrecht, G. Chem. Ber. 1987, 120,
1229-1237. (e) Larson, G. L.; Prieto, J . A.; Ortiz, E. Tetrahedron 1988,
44, 3781-3790. (f) Syldatk, C.; Stoffregen, A.; Brans, A.; Fritsche, K.;
Andree, H.; Wagner, F.; Hengelsberg, H.; Tafel, A.; Wuttke, F.; Zilch,
H.; Tacke, R. In Enzyme Engineering 9; Blanch, H. W., Klibanov, A.
M., Eds.; Ann. N.Y. Acad. Sci.; The New York Academy of Sciences:
New York, 1988; Vol. 542, pp 330-338. (g) Terunuma, D.; Yamamoto,
N.; Kizaki, H.; Nohira, H. Nippon Kagaku Kaishi 1990, 32, 451-456.
(h) Djerourou, A.-H.; Blanco, L. Tetrahedron Lett. 1991, 32, 6325-
6326. (i) Tacke, R.; Brakmann, S.; Wuttke, F.; Fooladi, J .; Syldatk, C.;
Schomburg, D. J . Organomet. Chem. 1991, 403, 29-41. (j) Tacke, R.;
Brakmann, S.; Kropfgans, M.; Strohmann, C.; Wuttke, F.; Lambrecht,
G.; Mutschler, E.; Proksch, P.; Schiebel, H.-M.; Witte, L. In Frontiers
of Organosilicon Chemistry; Bassindale, A. R., Gaspar, P. P., Eds.; The
Royal Society of Chemistry: Cambridge, U.K., 1991; pp 218-228. (k)
Tacke, R.; Wuttke, F.; Henke, H. J . Organomet. Chem. 1992, 424, 273-
286. (l) Yamamoto, K.; Kawanami, Y.; Miyazawa, M. J . Chem. Soc.,
Chem. Commun. 1993, 436-437. (m) Ohta, T.; Ito, M.; Tsuneto, A.;
Takaya, H. J . Chem. Soc., Chem. Commun. 1994, 2525-2526. (n)
Fukui, T.; Kawamoto, T.; Tanaka, A. Tetrahedron Asymmetry 1994,
5, 73-82. (o) Tacke, R.; Reichel, D.; Gu¨nther, K.; Merget, S. Z.
Naturforsch., B 1995, 50, 568-572. (p) Tacke, R.; Reichel, D.; Kropf-
gans, M.; J ones, P. G.; Mutschler, E.; Gross, J .; Hou, X.; Waelbroeck,
M.; Lambrecht, G. Organometallics 1995, 14, 251-262. (q) Huber, P.;
Bratovanov, S.; Bienz, S.; Syldatk, C.; Pietzsch, M. Tetrahedron
Asymmetry 1996, 7, 69-78. (r) Reichel, D.; Tacke, R.; J ones, P. G.;
Lambrecht, G.; Gross, J .; Mutschler, E.; Waelbroeck, M. In Organo-
silicon Chemistry II-From Molecules to Materials; Auner, N., Weis, J .,
Eds.; VCH: Weinheim, Germany, 1996; pp 231-236. (s) Wagner, S.
A.; Brakmann, S.; Tacke, R. In Organosilicon Chemistry II-From
Molecules to Materials; Auner, N., Weis, J ., Eds.; VCH: Weinheim,
Germany, 1996; pp 237-242. (t) Kobayashi, K.; Kato, T.; Unno, M.;
Masuda, S. Bull. Chem. Soc. J pn. 1997, 70, 1393-1401.
Resu lts a n d Discu ssion
En zym a tic Syn th eses of th e An tip od es of 1-4.
Gen er a l Asp ects. Numerous prochiral organic di-
esters and diols have been successfully subjected to
lipase-catalyzed enantioselective transesterifications
and hydrolyses, respectively.5 A typical example for this
is the enzymatic synthesis of the (R)- and (S)-enan-
tiomers of the monoester 3-hydroxy-2-phenylpropyl
acetate (3).6 Compound (R)-3 was prepared by an
enantioselective transesterification of the diol 7 using
immobilized porcine pancreas lipase (PPL) as the bio-
catalyst and methyl acetate as the acylation agent and
solvent. The antipode (S)-3 was obtained by an enan-
tioselective hydrolysis of the corresponding diester 11
in a phosphate buffer system (pH 7) using immobilized
PPL as the biocatalyst. We could demonstrate that
these synthetic methods can also be applied to prepare
the antipodes of the related centrochiral hydridoger-
manes (acetoxymethyl)(hydroxymethyl)phenylgermane
(1) and (acetoxymethyl)(4-fluorophenyl)(hydroxymeth-
yl)germane (2). Compounds (R)-1 and (R)-2 were pre-
pared by a PPL-catalyzed transesterification of the diols
5 and 6, respectively, whereas the corresponding an-
(4) Publications dealing with optically active germanium compounds
of the formula type R1R2GeR3R4: (a) Schwarz, R.; Lewinsohn, M. Ber.
Dtsch. Chem. Ges. 1931, 64, 2352-2358. (b) Brook, A. G.; Peddle, G.
J . D. J . Am. Chem. Soc. 1963, 85, 1869-1870. (c) Brook, A. G.; Peddle,
G. J . D. J . Am. Chem. Soc. 1963, 85, 2338-2339. (d) Bott, R. W.;
Eaborn, C.; Varma, I. D. Chem. Ind. (London) 1963, 614. (e) Eaborn,
C.; Simpson, P.; Varma, I. D. J . Chem. Soc. A 1966, 1133-1136. (f)
Eaborn, C.; Hill, R. E. E.; Simpson, P.; Brook, A. G.; MacRae, D. J
Organomet. Chem. 1968, 15, 241-243. (g) Eaborn, C.; Hill, R. E. E.;
Simpson, P. J . Organomet. Chem. 1972, 37, 251-265. (h) Eaborn, C.;
Hill, R. E. E.; Simpson, P. J . Organomet. Chem. 1972, 37, 267-274.
(i) Carre´, F.; Corriu, R. J . Organomet. Chem. 1974, 65, 349-359. (j)
Terunuma, D.; Kizaki, H.; Sato, T.; Masuo, K.; Nohira, H. Bull. Chem.
Soc. J pn. 1993, 66, 664-665. (k) Terunuma, D.; Masuo, K.; Kizaki,
H.; Nohira, H. Bull. Chem. Soc. J pn. 1994, 67, 160-164. (l) Tacke, R.;
Wagner, S. A.; Sperlich, J . Chem. Ber. 1994, 127, 639-642. (m) Tacke,
R.; Reichel, D.; J ones, P. G.; Hou, X.; Waelbroeck, M.; Gross, J .;
Mutschler, E.; Lambrecht, G. J . Organomet. Chem. 1996, 521, 305-
323. (n) Reference 3s.
tipodes (S)-1 and (S)-2 were obtained by a PPL-
catalyzed hydrolysis of the diesters 9 and 10. For
reasons of comparison, we also studied the analogous
enzymatic conversions of the corresponding carbon
(5) Drauz, K., Waldmann, H., Eds. Enzyme Catalysis in Organic
Synthesis; VCH: Weinheim, Germany, 1995; Vol. 1.
(6) Ramos Tombo, G. M.; Scha¨r, H.-P.; Fernandez i Busquets, X.;
Ghisalba, O. Tetrahedron Lett. 1986, 27, 5707-5710.

Centrochiral Hydridogermanes
Sch em e 1
Organometallics, Vol. 17, No. 9, 1998 1689
Sch em e 2
Sch em e 3
analogues 7 [f (R)-3)], 8 [f (R)-4], 11 [f (S)-3], and
12 [f (S)-4].
acid9 (20). In the first step, compound 20 was treated
with lithium aluminum hydride, followed by working
up with water, to give the diol 8 (yield 79%). Subse-
quent reaction with an excess of acetic anhydride and
triethylamine in diethyl ether yielded the corresponding
diacetate 12 (yield 95%).
Syn th eses of r a c-1-r a c-4. Compounds rac-1-rac-4
were used as references to monitor the kinetics of the
enzymatic transformations by gas chromatography and
to determine the enantiomeric purities of the biotrans-
formation products by various analytical methods. In
addition, compounds rac-2 and rac-4 served as starting
materials for their preparative liquid-chromatographic
resolution. The monoacetates rac-1-rac-4 were syn-
thesized by reaction of the corresponding diols 5-8 with
acetic anhydride and triethylamine in diethyl ether and
isolated by column chromatography on silica gel
(yields: rac-1, 50%; rac-2, 47%; rac-3, 59%; rac-4, 49%)
(Scheme 3).
E n zym a t ic Tr a n sest er ifica t ion s of 5-8. The
prochiral bis(hydroxymethyl)germanes 5 and 6 and the
corresponding carbon analogues 7 and 8 were trans-
formed enantioselectively into the (R)-enantiomers of
1-4 using a PPL-catalyzed (E.C.3.1.1.3) transesterifi-
cation with ethyl acetate (for 5, 6, and 8) or vinyl acetate
(for 7) (Scheme 4). Ethyl acetate and vinyl acetate
served as acylation agents and solvents. The enzymatic
transformations were carried out on a preparative scale
(substrate, 1 mmol; EtOAc (ViOAc), 25 mL; PPL, 1 g;
T, 30 °C; for further details, see the Experimental
Section). The reactions were monitored by gas-chro-
matographic analyses (see the Experimental Section)
and stopped when the formation of the corresponding
diacetates was detected. The products (R)-1-(R)-4 were
Syn th eses of th e Sta r tin g Ma ter ia ls for th e
En zym a tic Tr a n sfor m a tion s, Com p ou n d s 5-12.
Bis(hydroxymethyl)phenylgermane (5), (4-fluorophenyl)-
bis(hydroxymethyl)germane (6), bis(acetoxymethyl)-
phenylgermane (9), and bis(acetoxymethyl)(4-fluoro-
phenyl)germane (10) were synthesized according to
Scheme 1, starting from dichlorobis(chloromethyl)-
germane4l (13).
In the first step, chlorobis(chloromethyl)phenylgermane
(14) and chlorobis(chloromethyl)(4-fluorophenyl)ger-
mane (16) were synthesized by reaction of the germane
13 with phenylmagnesium bromide and (4-fluoro-
phenyl)magnesium bromide, respectively, in diethyl
ether. The corresponding bromogermanes 15 and 17
(formed by a chlorine/bromine exchange) were obtained
as byproducts. The respective mixtures 14/15 and 16/
17 were treated in the next step with sodium acetate
in dimethylformamide to give acetoxybis(acetoxymeth-
yl)phenylgermane (18) and acetoxybis(acetoxymethyl)-
(4-fluorophenyl)germane (19), respectively (yields re-
lated to 13: 18, 65%; 19, 65%). Subsequent reaction of
the germanes 18 and 19 with lithium aluminum hydride
in diethyl ether, followed by working up with water,
gave compounds 5 (yield 74%) and 6 (yield 74%).
Treatment of 5 and 6 with an excess of acetic anhydride
and triethylamine in diethyl ether finally yielded com-
pounds 9 (yield 94%) and 10 (yield 91%).
2-Phenyl-1,3-propanediol7 (7) and 2-phenyl-1,3-pro-
panediyl diacetate8 (11) were prepared according to the
literature. The corresponding p-fluoro derivatives 2-(4-
fluorophenyl)-1,3-propanediol (8) and 2-(4-fluorophenyl)-
1,3-propanediyl diacetate (12) were synthesized accord-
ing to Scheme 2, starting from (4-fluorophenyl)malonic
(9) (a) Synthesized analogously to that of (4-chlorophenyl)malonic
acid: Ivanoff, D.; Spassoff, A. Bull. Soc. Chim. 1930, 49, 19-23. (b)
Alternative synthesis of 20: Miyamoto, K.; Ohta, H. Eur. J . Biochem.
1992, 210, 475-481.
(7) Searles, S., J r.; Nickerson, R. G.; Witsiepe, W. K. J . Org. Chem.
1959, 24, 1839-1844.
(8) Heslinga, A. Recueil 1959, 78, 473-479.

1690 Organometallics, Vol. 17, No. 9, 1998
Tacke et al.
Ta ble 2. Exp er im en ta l Da ta a for th e
Sch em e 4
P P L-Ca ta lyzed Hyd r olyses of 9-12
[F or m a tion of (S)-1-(S)-4]
ee value (%)
reaction
20
d
compd
time (min)
yield (%)
1Hb
19Fc
[R]
366
(S)-1
(S)-2
(S)-3
(S)-4
375
315
420
240
48
62
63
63
84
94
81
88
84
94
81
86
-5.8
-6.4
+15.7
+18.3
a
The data (mean values) given are based on three single
enzymatic transformations (for the experimental conditions, see
b
the Experimental Section). Data obtained by 1H NMR studies
d
(see text). c Data obtained by 19F NMR studies (see text). Specific
optical rotation determined in acetone (c, 2.5).
80 mg; T, 30 °C]. The reactions were monitored by gas-
chromatographic analyses (see the Experimental Sec-
tion) and stopped when the formation of the correspond-
ing diols was detected. The products (S)-1-(S)-4 were
isolated and subsequently purified by preparative layer
chromatography on silica gel. Their enantiomeric puri-
ties were determined by NMR-spectroscopic investiga-
tions. Alternatively, the ee values were established by
liquid-chromatographic [(S)-1-(S)-4] and gas-chromato-
graphic [(S)-2, (S)-4] studies (see below). Selected
experimental data (mean values for three single experi-
ments) for the enzymatic hydrolyses of 9-12 are sum-
marized in Table 2.
The conversion rates of the hydrolyses of the bis-
(acetoxymethyl)germanes 9 and 10 were found to be
similar to those of the corresponding carbon analogues
11 and 12. The products (S)-1-(S)-4 were isolated in
reasonable yields with high enantiomeric purities. The
ee values determined by NMR-spectroscopic studies (see
Table 2) were in good agreement with those obtained
by the liquid-chromatographic and gas-chromatographic
investigations (data not given). Further attempts to
optimize the enzymatic hydrolyses of 9-12 were not
made.
Con figu r a t ion a l St a b ilit y of t h e An t ip od es of
1-4. In contrast to the configurationally stable anti-
podes of 3 and 4, the corresponding germanes (R)-1, (S)-
1, (R)-2, and (S)-2 were found to undergo a partial
racemization (up to ca. 5%) upon heating (Kugelrohr
distillation, 120 °C, 0.01 Torr). However, storage of the
purified antipodes of the germanes 1 and 2 at -20 °C
for 6 months did not lead to a significant degree of
racemization.
P r ep a r a tive Liqu id -Ch r om a togr a p h ic Resolu -
tion of r a c-2 a n d r a c-4. The germanium/carbon
analogues rac-2 and rac-4 were resolved by preparative
liquid chromatography on cellulose tribenzoate using
the solvent system n-hexane/diisopropyl ether (50:50,
v/v) and n-hexane/tert-butyl methyl ether (50:50, v/v),
respectively. The yields were 80% (enantiomers of 2;
eight runs each on a 500-mg scale) and 97% (enantio-
mers of 4; three runs each on an 850-mg scale). The
enantiomeric purities of the resolved antipodes were as
follows: (R)-2, 97% ee; (S)-2, 97% ee; (R)-4, >99% ee;
(S)-4, >98% ee (ee values determined by liquid chro-
matography). To the best of our knowledge, the resolu-
tion of rac-2 is the first example of a preparative liquid-
chromatographic separation of the antipodes of a
centrochiral germane.
Ta ble 1. Exp er im en ta l Da ta a for th e
P P L-Ca ta lyzed Tr a n sester ifica tion s of 5-8
[F or m a tion of (R)-1-(R)-4]
ee value (%)
reaction
time (min)
20
d
compd
yield (%)
1Hb
19Fc
[R]
366
(R)-1e
(R)-2e
(R)-3f
(R)-4e
150
75
50
76
77
76
76
93
87
89
89
93
86
89
90
+6.4
+5.9
-17.5
-19.0
240
a
The data (mean values) given are based on three single
enzymatic transformations (for the experimental conditions, see
b
the Experimental Section). Data obtained by 1H NMR studies
d
(see text). c Data obtained by 19F NMR studies (see text). Specific
optical rotation determined in acetone (c, 2.5). e Ethyl acetate as
acyl donor. f Vinyl acetate as acyl donor.
isolated and subsequently purified by preparative layer
chromatography on silica gel. Their enantiomeric puri-
ties were determined by NMR-spectroscopic investiga-
tions (see below). Alternatively, the ee values were
established by liquid-chromatographic [(R)-1-(R)-4] and
gas-chromatographic [(R)-2, (R)-4)] studies (see below).
Selected experimental data (mean values for three
single experiments) for the enzymatic transesterifica-
tions of 5-8 are summarized in Table 1.
The conversion rates of the transesterifications of the
bis(hydroxymethyl)germanes 5 and 6 with ethyl acetate
were found to be higher than those of the corresponding
carbon analogues 7 and 8. As the conversion rate of 7
was particularly low (ca. 50% conversion after 48 h),
vinyl acetate was used as the acyl donor for the
synthesis of (R)-3. The products (R)-1-(R)-4 were
isolated in reasonable yields with high enantiomeric
purities. The ee values determined by NMR-spectro-
scopic studies (see Table 1) were in good agreement with
those obtained by the liquid-chromatographic and gas-
chromatographic investigations (data not given). Fur-
ther attempts to optimize the enzymatic transesterifi-
cations of 5-8 were not made.
En zym a tic Hyd r olyses of 9-12. The prochiral bis-
(acetoxymethyl)germanes 9 and 10 and the correspond-
ing carbon analogues 11 and 12 were transformed
enantioselectively into the (S)-enantiomers of 1-4 using
a PPL-catalyzed (E.C.3.1.1.3) hydrolysis in a phosphate
buffer/tetrahydrofuran system (25:1, v/v) (Scheme 4).
The enzymatic transformations were carried out on a
preparative scale [substrate, 1 mmol; So¨rensen phos-
phate buffer (pH 7), 25 mL; tetrahydrofuran, 1 mL; PPL,
The yields and enantiomeric purities of the germanes
(R)-2 and (S)-2 were lower than those obtained for their

Centrochiral Hydridogermanes
Sch em e 5
Organometallics, Vol. 17, No. 9, 1998 1691
Ta ble 3. Reten tion Tim esa for th e An a lytica l
Liqu id -Ch r om a togr a p h ic (HP LC) Sep a r a tion of
th e (R)- a n d (S)-En a n tiom er s of 1-4
retention
retention
compd
time (min)
compd
time (min)
(R)-1
(S)-1
(R)-2
(S)-2
116
105
90
(R)-3
(S)-3
(R)-4
(S)-4
48
39
24
54
71
a
Determined for the racemic mixtures; for experimental condi-
tions, see the Experimental Section.
Ta ble 4. Reten tion Tim esa for th e An a lytica l
Ga s-Ch r om a togr a p h ic Sep a r a tion s of th e
Tr iflu or oa ceta tes of th e (R)- a n d (S)-En a n tiom er s
of 2 a n d 4
retention
retention
compd
time (min)
compd
time (min)
(R)-2
(S)-2
29.50
29.70
(R)-4
(S)-4
29.20
29.50
carbon analogues (R)-4 and (S)-4. This observation can
be explained in terms of a decomposition of the ger-
manes. The nature of this process (which even pro-
ceeded after the chromatographic separation was fin-
ished) is unknown.10 Interestingly, this particular type
of decomposition was not observed for the samples
obtained by the enzymatic transformations. However,
by analogy with the behavior of the products prepared
by biotransformation, the samples obtained by liquid
chromatography were also found to undergo a partial
racemization (up to ca. 5%) upon heating (Kugelrohr
distillation, 120 °C, 0.01 Torr).
a
Determined for the racemic mixtures; for experimental condi-
tions, see the Experimental Section.
chromatographic method was used to determine the
enantiomeric purities of the antipodes of 2 and 4
obtained by enzymatic transformations. To the best of
our knowledge, the resolution of rac-2 is the first
example of an analytical gas-chromatographic separa-
tion of the enantiomers of a centrochiral germane.
Absolu te Con figu r a tion of th e An tip od es of 1-4.
The stereochemical course of the PPL-catalyzed trans-
esterification of the prochiral diol 7 with methyl acetate
[formation of (R)-3] has already been reported in the
literature.6 We observed the same stereochemistry
when using ethyl acetate instead of methyl acetate as
the acyl donor. This result is in agreement with the
stereochemical course of a series of PPL-catalyzed
transesterifications with related 2-organyl-1,3-pro-
panediols.5,6 Thus, it is likely to assume that the
transesterifications of the diols 5, 6, and 8 proceed with
the same stereochemistry [formation of (R)-1, (R)-2, and
(R)-4]. On the basis of analogous considerations, the
(S)-configuration can be assumed for the products
obtained by the PPL-catalyzed hydrolysis of the prochiral
diacetates 9-12 [formation of (S)-1-(S)-4] (in this
context, see also refs 5 and 6). In the case of the (R)-
and (S)-enantiomers of 3 and 4, assignment of the
absolute configurations by this particular biochemical
correlation is strongly supported by chiroptical correla-
tions. As expected, the chiroptical properties (specific
optical rotations at 366, 436, 546, 578, and 589 nm;
acetone, c ) 2.5) of the levorotatory enantiomers (R)-3
and (R)-4 [dextrorotatory enantiomers (S)-3 and (S)-4]
were found to be very similar. In contrast, the chir-
optical properties of the (R)- and (S)-enantiomers of the
germanes 1 and 2 differ significantly from those deter-
mined for the antipodes of their corresponding carbon
analogues 3 and 4. Compounds (R)-1 and (R)-2 [(S)-1
and (S)-2] are the dextrorotatory (levorotatory) enanti-
omers, whereas the carbon analogues (R)-3 and (R)-4
[(S)-3 and (S)-4] show the opposite sign of optical
rotation (Figure 1). However, this surprising observa-
tion does not contradict the absolute configurations of
the germanes (R)-1, (S)-1, (R)-2, and (S)-2 assigned on
the basis of the biochemical correlation. Additional
experimental studies have shown that removal of the
Deter m in a tion of th e En a n tiom er ic P u r ities of
th e An tip od es of 1-4 by 1H a n d 19F NMR Sp ec-
tr oscop y. The enantiomeric purities of the antipodes
of 1-4 were determined, after derivatization with (S)-
R-methoxy-R-(trifluoromethyl)phenylacetyl chloride [(S)-
1
MTPA-Cl] (Scheme 5), by H and 19F NMR studies of
the corresponding diastereomeric (R)-MTPA esters 29a-
32a and 29b-32b (quantification of the diastereomers
by integration of characteristic resonance signals).
Generally, both NMR-spectroscopic methods gave al-
most the same results. In addition, these results were
in good agreement with those obtained by the liquid-
chromatographic and gas-chromatographic studies.
Deter m in a tion of th e En a n tiom er ic P u r ities of
th e An tip od es of 1-4 by Liqu id Ch r om a togr a p h y.
Compounds rac-1-rac-4 were resolved by analytical
liquid chromatography (HPLC) using cellulose tribenz-
oate as the chiral stationary phase. The retention times
of the (R)- and (S)-enantiomers of 1-4 are listed in
Table 3. This liquid-chromatographic method was used
to determine the enantiomeric purities of the antipodes
of 1-4 obtained by enzymatic transformations and
liquid-chromatographic resolutions.
Deter m in a tion of th e En a n tiom er ic P u r ities of
th e An tip od es of 2 a n d 4 by Ca p illa r y Ga s Ch r o-
m a togr a p h y. Compounds rac-2 and rac-4 were ad-
ditionally resolved, after conversion into the correspond-
ing trifluoroacetates, by analytical capillary gas
chromatography using a chemically modified cyclodex-
trin column. The retention times of the (R)- and (S)-
enantiomers of 2 and 4 are listed in Table 4. This gas-
(10) This decomposition is probably supported by trace components
arising from the stationary phase and/or the eluents. This process can
be stopped by an additional purification by layer chromatography on
silica gel and/or distillation (Kugelrohr distillation, 120 °C, 0.01 Torr).
However, the distillation leads to a decrease in enantiomeric purity.

1692 Organometallics, Vol. 17, No. 9, 1998
Tacke et al.
F igu r e 1. Specific optical rotations of the antipodes of the
germanes 1 and 2 (above) and the antipodes of their carbon
analogues 3 and 4 (below) determined at 366, 436, 546,
578, and 589 nm in acetone (c, 2.5; T, 20 °C). The
(R)-enantiomers were prepared by enzymatic transesteri-
fications, the (S)-enantiomers by enzymatic hydrolyses (see
text).
alcohol or ester functionality of the biotransformation
products (R)-1-(R)-4 and (S)-1-(S)-4 by derivatization
(see next section) leads to similar chiroptical properties
of the (R)- and (S)-enantiomers of the respective Ge/C
analogues (Figure 2). Thus, the respective dextrorota-
tory Ge/C pairs (S)-21/(S)-23, (S)-22/(S)-24, (S)-25/(S)-
F igu r e 2. Specific optical rotations of the Ge/C analogues
(R)-2/(R)-4 (above), (S)-22/(S)-24 (middle), and (S)-26/(S)-
28 (below) determined at 366, 436, 546, 578, and 589 nm
in acetone (c, 2.5; T, 20 °C). Compounds (R)-2 and (R)-4
were prepared by enzymatic transesterifications; com-
pounds (S)-22, (S)-24, (S)-26, and (S)-28 were synthesized
from the corresponding biotransformation products (see
text).
are trifunctional compounds containing a GeH moiety,
an alcoholic OH group, and an ester function [ROC(O)-
Me]. To demonstrate that these compounds can be used
as starting materials for the synthesis of further opti-
cally active hydridogermanes, reactions at their alco-
holic OH groups and ester moieties were carried out.
For reasons of comparison, the corresponding carbon
analogues (R)-3, (S)-3, (R)-4, and (S)-4 were included
27, and (S)-26/(S)-28 display similar chiroptical prop-
erties. The same holds true for the corresponding
levorotatory Ge/C pairs (R)-21/(R)-23, (R)-22/(R)-24, (R)-
25/(R)-27, and (R)-26/(R)-28. These results additionally
support the assignment of the absolute configurations
of the germanes (R)-1, (S)-1, (R)-2, and (S)-2. The
differences in the chiroptical properties observed for the
Ge/C analogues (R)-1/(R)-3, (S)-1/(S)-3, (R)-2/(R)-4, and
(S)-2/(S)-4 cannot yet be explained.11
(11) One may speculate about different conformations of the corre-
sponding Ge/C analogues caused by different O-H‚‚‚O interactions
between their OH and OAc groups (the different covalent radii of
germanium and carbon may affect this hydrogen bonding system).
Removal of one of the two functionalities should lead to more similar
conformations of the Ge/C analogues.
Der iva tiza tion of th e An tip od es of 1-4. The
biotransformation products (R)-1, (S)-1, (R)-2, and (S)-2

Centrochiral Hydridogermanes
Sch em e 6
Organometallics, Vol. 17, No. 9, 1998 1693
Sch em e 7
germanes R1R2R3GeH were known. To the best of our
knowledge, the antipodes of 34,4b 35,4d,e and 364g as well
as (+)-374i are the only examples of this particular type
of compound. Their syntheses are based on the resolu-
tion of chiral Ge-functional precursors R1R2R3GeX via
fractional crystallization of appropriate diastereomeric
derivatives and subsequent chemical transformation of
the resolved germanes (R1R2R3GeX f R1R2R3GeH). The
enantiomeric purities of these optically active com-
pounds have not been reported.
We have now succeeded for the first time in preparing
the (R)- and (S)-enantiomers of centrochiral hydrido-
triorganylgermanes by enantioselective enzymatic trans-
formations [synthesis of (R)-1, (S)-1, (R)-2, and (S)-2]
and by preparative liquid-chromatographic resolution
on a chiral stationary phase [preparation of (R)-2 and
(S)-2]. In addition, we have demonstrated that the
antipodes of the trifunctional compounds 1 and 2 (GeH,
COH, and COAc functionalities) can be used as starting
materials for the preparation of further optically active
hydridotriorganylgermanes [syntheses of the (R)- and
(S)-enantiomers of 20, 21, 25, and 26 by reaction at the
COH and COAc groups]. As optically active hydrido-
germanes have been shown to be useful synthons for
the preparation of further optically active derivatives
(R1R2R3GeH f R1R2R3GeX),4c,e-i the antipodes of 1, 2,
20, 21, 25, and 26 can also be regarded as potential
starting materials for the synthesis of a variety of
optically active centrochiral germanes. Reactions at the
organic functional groups and at the GeH moiety as well
offer a wide range of synthetic possibilities.
in these studies. As shown in Scheme 6, the biotrans-
formation products (R)-1-(R)-4 and (S)-1-(S)-4 were
converted into the derivatives (S)-21-(S)-28 and (R)-
21-(R)-28, respectively. Reaction of (R)-1-(R)-4 with
tert-butylchlorodiphenylsilane and imidazole in di-
methylformamide yielded the corresponding O-silyl
derivatives (S)-21-(S)-24 (yields 79-82%). The anti-
podes (R)-21-(R)-24 were obtained analogously, start-
ing from (S)-1-(S)-4 (yields 78-85%). Subsequent
reaction of the esters (S)-21-(S)-24 and (R)-21-(R)-24
with methanol, in the presence of potassium carbonate,
yielded the corresponding alcohols (S)-25-(S)-28 and
(R)-25-(R)-28, respectively (yields 76-87%). As the
center of chirality (central germanium or carbon atom)
is not involved in these chemical transformations,
retention of absolute configuration can be assumed for
the reaction sequences 1-4 f 21-24 f 25-28.
As investigated exemplarily for the reactions (R)-2 f
(S)-22 f (S)-26 and (S)-2 f (R)-22 f (R)-26, the
enantiomeric purities of the germanes were not affected
by these chemical transformations. This was demon-
strated, after derivatization of (S)-26 and (R)-26 with
(S)-R-methoxy-R-(trifluoromethyl)phenylacetyl chloride
Generally, biocatalysis and liquid-chromatographic
resolution on chiral stationary phases offer interesting
fields of application for preparative organometallic
chemistry. Both methods are characterized by rela-
tively mild conditions, which is very advantageous for
the preparation of compounds with limited chemical and
thermal stability.
1
[(S)-MTPA-Cl] (Scheme 7), by H and 19F NMR studies
of the corresponding (R)-MTPA ester 33a /33b. The
enantiomeric purities of the derivatives (S)-26 and (R)-
26 were found to be almost the same as those deter-
mined for the biotransformation products (R)-2 and (S)-
2, respectively.
Exp er im en ta l Section
Gen er a l P r oced u r es. All reactions were carried out under
dry nitrogen unless otherwise indicated. The organic solvents
used for the nonenzymatic syntheses were dried and purified
according to standard procedures and stored under nitrogen.
1H and 13C NMR spectra were recorded at room temperature
on a Bruker AMX-400 (1H, 400.1 MHz; 13C, 100.6 MHz), Bruker
Con clu sion
When the investigations described in this paper were
started, only a few optically active hydridotriorganyl-

1694 Organometallics, Vol. 17, No. 9, 1998
Tacke et al.
DRX-300 (1H, 300.1 MHz; 13C, 75.5 MHz), or Bruker AC-250
NMR spectrometer (1H, 250.1 MHz; 13C, 62.9 MHz). 19F NMR
spectra were recorded at room temperature on a Bruker AMX-
400 NMR spectrometer (19F, 376.4 MHz). C6D6 was used as
solvent. Chemical shifts (ppm) were determined relative to
internal C6D5H (1H, δ 7.28), C6D6 (13C, δ 128.0), and CFCl3
(19F, δ 0). Assignment of the 13C NMR data was supported by
H, 7.4. Calcd for (S)-4 (C11H13FO3): C, 62.26; H, 6.17.
Found: C, 62.0; H, 5.9.
Mon itor in g of th e Tim e Cou r se of th e En zym a tic
Tr a n sfor m a tion s by Ca p illa r y Ga s Ch r om a togr a p h y. For
monitoring the enzymatic conversions, 1-mL samples of the
reaction mixtures were taken after various periods of time and
analyzed by capillary gas chromatography. For this purpose,
the samples taken from the enzymatic transesterifications
were diluted with ethyl acetate (1 mL) and 1 µL of the resulting
solution was injected into the gas chromatograph [gas chro-
matograph, Shimadzu GC-14A; capillary column, SE-30 CB
(Ziemer, 6232.028), 10 m; carrier gas, nitrogen; temperature
program, 80 °C (2 min) to 280 °C (20 min) with 10 °C/min;
injector temperature, 200 °C; split, 1:50; detector, FID; detector
temperature, 320 °C]. In the case of the enzymatic hydrolyses,
the aqueous samples were extracted with diethyl ether (1 mL)
and 1 µL of the organic extract was injected into the gas
chromatograph. The retention times (min) were as follows:
1, 9.1; 5, 8.3; 9, 10.2. -2, 9.0; 6, 8.4; 10, 10.0. -3, 7.9; 7, 6.7;
11, 9.1. -4, 8.1; 8, 6.9; 12, 9.2.
P r ep a r a tive Liqu id -Ch r om a togr a p h ic Resolu tion of
r a c-2 a n d r a c-4. The (R)- and (S)-enantiomers of 2 and 4
were obtained by liquid-chromatographic separation of rac-2
and rac-4, respectively, on cellulose tribenzoate (10-20 µm;
Riedel-deHae¨n, 39852). The experimental conditions were as
follows: LC pump, Shimadzu LC8-A; detector, Knauer VW
monitor; integrator, Shimadzu C-R3A; column (100 mm i.d.
× 130 mm), Merck Superformance; eluent, n-hexane/diisopro-
pyl ether (50:50, v/v) for rac-2 and n-hexane/tert-butyl methyl
ether (50:50, v/v) for rac-4 (HPLC-grade solvents purchased
from Merck); detection, 215 nm; T, ambient temperature;
injection volume, 15 mL (500 mg of the sample material in 15
mL of 2-propanol) for rac-2 and 20 mL (850 mg of the sample
material in 20 mL of 2-propanol) for rac-4. Eight runs each
on a 500-mg scale (rac-2) and three runs each on a 850-mg
scale (rac-4), respectively, were performed. The solvents of
the respective fractions obtained [(R)-2, second fraction; (S)-
2, first fraction; (R)-4, first fraction; (S)-4, second fraction] were
removed immediately after the chromatographic separation
(rotary evaporator, 30 °C, 150 Torr), and the respective
residues were combined and then stored at -18 °C. The yields
and enantiomeric purities of the separated enantiomers (color-
less liquids) were as follows: (R)-2, 80%, 97% ee; (S)-2, 80%,
97% ee; (R)-4, 97%, >99% ee; (S)-4, 97%, >98% ee (ee values
determined by analytical liquid chromatography). Anal.
Calcd for (R)-2 (C10H13FGeO3): C, 44.03; H, 4.80. Found: C,
43.6; H, 4.7. Calcd for (S)-2 (C10H13FGeO3): C, 44.03; H, 4.80.
Found: C, 43.5; H, 4.8. Calcd for (R)-4 (C11H13FO3): C, 62.26;
H, 6.17. Found: C, 61.5; H, 6.3. Calcd for (S)-4 (C11H13FO3):
C, 62.26; H, 6.17. Found: C, 61.5; H, 6.1.
1
DEPT experiments. Analysis and assignment of the H NMR
data was partially supported by simulations using the
WINDAISY software package (version 4.0, Bruker). Mass
spectra were obtained with a Varian MAT-711 (EI MS, 70 eV;
FI MS, 11 kV), Finnigan MAT-8430 (EI MS, 70 eV; CI MS,
isobutane as reactant gas), or Finnigan MAT-8200 mass
spectrometer (EI MS, 70 eV). The selected m/z values given
refer to the isotopes 1H, 12C, 16O, 19F, 28Si, 35Cl, and 74Ge.
Optical rotations were measured with a POL S-2-5 polarimeter
(L.O.T.-Oriel) using freshly prepared solutions; acetone (Uva-
sol; Merck, 100022) served as solvent. Preparative layer
chromatography was performed with silica gel TLC plates
(stationary phase, silica gel 60 F254; layer thickness, 2 mm;
Merck, 5717). Preparative column chromatography [column:
40 mm i.d. × 250 mm (rac-1, rac-2); 25 mm i.d. × 300 mm
(rac-3); 60 mm i.d. × 200 mm (rac-4)] was performed using
silica gel as stationary phase (silica gel 60, 0.063-0.200 mm;
Merck, 15111).
P r ep a r a tion of (R)-1-(R)-4 by En zym a tic Tr a n sester i-
fica tion (Gen er a l P r oced u r e). Porcine pancreas lipase
(E.C.3.1.1.3; Fluka, 62300; 2.55 U/mg) (1 g) was added to a
solution of the respective diol 5-8 (1 mmol) in ethyl acetate
(25 mL) (LiChrosolv; Merck, 100868) (5, 6, 8) or vinyl acetate
(25 mL) (Aldrich, V150-3) (7). The suspension was shaken at
the air in a water bath (30 °C, 145 rpm) and the enzymatic
transformation monitored by gas chromatography (see below).
After the formation of the respective diacetates 9-12 was
detected, the biotransformation was stopped by centrifugation.
The solvent was removed under reduced pressure (rotary
evaporator) and the residue purified by preparative layer
chromatography on silica gel [diethyl ether/n-hexane (2:1, v/v)].
Experimental data for the enzymatic transesterifications are
listed in Table 1. The NMR-spectroscopic and mass-spectro-
metric data of (R)-1-(R)-4 were identical with those obtained
for the corresponding racemic mixtures rac-1-rac-4 (see
below). Anal. Calcd for (R)-1 (C10H14GeO3): C, 47.13; H, 5.54.
Found: C, 46.8; H, 5.8. Calcd for (R)-2 (C10H13FGeO3): C,
44.03; H, 4.80. Found: C, 43.8; H, 4.8. Calcd for (R)-3
(C11H14O3): C, 68.02; H, 7.27. Found: C, 67.7; H, 7.2. Calcd
for (R)-4 (C11H13FO3): C, 62.26; H, 6.17. Found: C, 61.7; H,
6.0.
P r ep a r a tion of (S)-1-(S)-4 by En zym a tic Hyd r olysis
(Gen er a l P r oced u r e). Porcine pancreas lipase (E.C.3.1.1.3;
Fluka, 62300; 2.55 U/mg) (80 mg) was added to a mixture of
the respective diacetate 9-12 (1 mmol) in tetrahydrofuran (1
mL) and So¨rensen phosphate buffer (pH 7) (25 mL). The
suspension was shaken at the air in a water bath (30 °C, 145
rpm) and the enzymatic transformation monitored by gas
chromatography (see below). After the formation of the
respective diols 5-8 was detected, the biotransformation was
stopped by centrifugation. The aqueous solution was extracted
with diethyl ether (3 × 20 mL) and the combined organic layers
dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure (rotary evaporator) and the residue purified
by preparative layer chromatography on silica gel [diethyl
ether/n-hexane (2:1, v/v)]. Experimental data for the enzy-
matic hydrolyses are listed in Table 2. The NMR-spectroscopic
and mass-spectrometric data of (S)-1-(S)-4 were identical with
those obtained for the corresponding racemic mixtures rac-
1-rac-4 (see below). Anal. Calcd for (S)-1 (C10H14GeO3): C,
47.13; H, 5.54. Found: C, 46.8; H, 5.8. Calcd for (S)-2
(C10H13FGeO3): C, 44.03; H, 4.80. Found: C, 43.8; H, 4.7.
Calcd for (S)-3 (C11H14O3): C, 68.02; H, 7.27. Found: C, 67.6;
r a c -( Ac e t o x y m e t h y l ) ( h y d r o x y m e t h y l ) p h e n y l -
ger m a n e (r a c-1). Acetic anhydride (960 mg, 9.40 mmol) and
triethylamine (951 mg, 9.40 mmol) were added to a solution
of 5 (2.00 g, 9.40 mmol) in diethyl ether (100 mL). After the
mixture was heated under reflux for 8 h and stirred at room
temperature for 12 h, the organic layer was extracted with
water (3 × 30 mL) and then dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure (rotary
evaporator) and the product isolated and purified by column
chromatography on silica gel [eluent diethyl ether/n-hexane
(1:1, v/v); Rf(9) > Rf(rac-1) > Rf(5)] to give rac-1 in 50% yield
as a colorless liquid (1.20 g, 4.71 mmol). [In addition, the diol
5 (200 mg, 940 µmol; yield 10%) and the diacetate 9 (640 mg,
2.16 mmol; yield 23%) were isolated as colorless liquids.] 1H
NMR (400.1 MHz, C6D6): δ 1.66 (s, 3 H, CCH3), 2.2 (br s, 1 H,
OH), 4.02 (δA(A′)), 4.31 (δK), 4.34 (δL), and 4.89 (δX) [Ge(CHAHA′-
3
3
2
OH)(CHKHLOAc)HX, J AX + J A′X ) 4.4 Hz, J KL ) -12.3 Hz,
3
3J KX ) 1.6 Hz, J LX ) 3.0 Hz], 7.23-7.28 and 7.55-7.61 (m, 5
H, GeC6H5). 13C NMR (62.9 MHz, C6D6): δ 20.1 (CCH3), 53.0
(GeCH2O), 55.0 (GeCH2O), 128.3 (C-3/C-5, GeC6H5), 129.4 (C-
4, GeC6H5), 134.5 (C-1, GeC6H5), 135.9 (C-2/C-6, GeC6H5),

Centrochiral Hydridogermanes
Organometallics, Vol. 17, No. 9, 1998 1695
171.6 (CdO). EI MS: m/z 256 [<1%, M+], 225 [100%, M+
CH2OH]. Anal. Calcd for C10H14GeO3: C, 47.13; H, 5.54.
Found: C, 47.3; H, 5.5.
-
Bis(h yd r oxym eth yl)p h en ylger m a n e (5). A solution of
18 (14.0 g, 39.4 mmol) in diethyl ether (50 mL) was added
dropwise at 0 °C over 1 h to a stirred suspension of lithium
aluminum hydride (3.12 g, 82.2 mmol) in diethyl ether (250
mL). The reaction mixture was heated under reflux for 6 h
and then stirred for a further 16 h at room temperature. After
the mixture was cooled to 0 °C, a saturated aqueous solution
of sodium sulfate was added cautiously in 10-mL portions until
a white coagulum was formed. The organic layer was decanted
and the coagulum extracted with diethyl ether (6 × 50 mL).
The combined organic extracts were dried over anhydrous
Na2SO4, and the solvent was removed under reduced pressure
(rotary evaporator). The crude product was purified by
distillation in vacuo (Vigreux column) to give 5 in 74% yield
as a colorless liquid (6.20 g, 29.1 mmol); bp 130 °C/ 0.01 Torr.
1H NMR (400.1 MHz, C6D6): δ 2.1 (br s, 2 H, OH), 3.97-4.08
[m, 4 H, Ge(CHAHBO)(CHA′HB′O)], 4.81 [m, center, 1 H, GeH),
7.24-7.30 and 7.59-7.65 (m, 5 H, GeC6H5). 13C NMR (62.9
MHz, C6D6): δ 53.6 (GeCH2O), 128.5 (C-3/C-5, GeC6H5), 129.3
(C-4, GeC6H5), 135.0 (C-2/C-6, GeC6H5), 135.3 (C-1, GeC6H5).
EI MS: m/z 213 [2%, M+ - H], 183 [70%, M+ - CH2OH], 91
[100%, C7H7+]. Anal. Calcd for C8H12GeO2: C, 45.16; H, 5.68.
Found: C, 45.1; H, 5.6.
r a c-(Acetoxym eth yl)(4-flu or oph en yl)(h ydr oxym eth yl)-
ger m a n e (r a c-2). This compound was prepared analogously
to the synthesis of rac-1 by addition of acetic anhydride (995
mg, 9.75 mmol) and triethylamine (987 mg, 9.75 mmol) to a
solution of 6 (2.25 g, 9.75 mmol) in diethyl ether (125 mL).
After column-chromatographic separation on silica gel [eluent
diethyl ether/n-hexane (1:1, v/v; 6 was eluated with ethyl
acetate); Rf(10) > Rf(rac-2) > Rf(6)], rac-2 was isolated in 47%
yield as a colorless liquid (1.24 g, 4.55 mmol). [In addition,
the diol 6 (231 mg, 1.00 mmol; yield 10%) was isolated as a
white solid and the diacetate 10 (601 mg, 1.91 mmol; yield
20%) as a colorless liquid.] 1H NMR (400.1 MHz, C6D6): δ
1.65 (s, 3 H, CCH3), 1.9 (br s, 1 H, OH), 3.93 (δA(A′)), 4.22 (δK),
3
4.26 (δL), and 4.78 (δX) [Ge(CHAHA′OH)(CHKHLOAc)HX, J AX
3
2
3
3
+ J A′X ) 3.8 Hz, J KL ) -12.3 Hz, J KX ) 1.6 Hz, J LX ) 3.0
Hz], 6.90-6.98 and 7.34-7.40 (m, 4 H, GeC6H4F). 13C NMR
(62.9 MHz, C6D6): δ 20.1 (CCH3), 53.1 (GeCH2O), 55.0
(GeCH2O), 115.7 (d, 2J CF ) 19.5 Hz, C-3/C-5, GeC6H4F), 129.8
(d, 4J CF ) 4.3 Hz, C-1, GeC6H4F), 136.9 (d, 3J CF ) 7.3 Hz, C-2/
C-6, GeC6H4F), 164.2 (d, 1J CF ) 247.8 Hz, C-4, GeC6H4F), 171.7
(CdO). EI MS: m/z 274 [<1%, M+], 243 [100%, M+ - CH2OH].
Anal. Calcd for C10H13FGeO3: C, 44.03; H, 4.80. Found: C,
43.8; H, 4.8.
(4-Flu or oph en yl)bis(h ydr oxym eth yl)ger m an e (6). This
compound was prepared analogously to the synthesis of 5 by
addition of a solution of 19 (5.30 g, 14.2 mmol) in diethyl ether
(20 mL) to a suspension of lithium aluminum hydride (1.62 g,
42.7 mmol) in diethyl ether (100 mL). The crude product was
distilled in vacuo (Vigreux column) to give 6 in 74% yield as a
colorless liquid (crystallization on cooling to room temperature)
(2.44 g, 10.6 mmol); bp 130 °C/0.01 Torr. 1H NMR (400.1 MHz,
C6D6): δ 2.3 (br s, 2 H, OH), 3.90-4.05 [m, 4 H, Ge(CHAHBO)-
(CHA′HB′O)], 4.73 [m, center, 1 H, GeH), 6.93-7.02 and 7.37-
7.46 (m, 4 H, GeC6H4F). 13C NMR (62.9 MHz, C6D6): δ 53.6
(GeCH2O), 115.8 (d, 2J CF ) 20.1 Hz, C-3/C-5, GeC6H4F), 130.4
(d, 4J CF ) 4.3 Hz, C-1, GeC6H4F), 136.9 (d, 3J CF ) 6.2 Hz, C-2/
r a c-3-Hyd r oxy-2-p h en ylp r op yl Aceta te (r a c-3). This
compound was prepared analogously to the synthesis of rac-1
by addition of acetic anhydride (671 mg, 6.57 mmol) and
triethylamine (665 mg, 6.57 mmol) to a solution of 7 (1.00 g,
6.57 mmol) in diethyl ether (50 mL). After column-chromato-
graphic separation on silica gel [eluent diethyl ether/n-hexane
(1:1, v/v); Rf(11) > Rf(rac-3) > Rf(7)], rac-3 was isolated in 59%
yield as a colorless liquid (750 mg, 3.86 mmol). [In addition,
the diol 7 (180 mg, 1.18 mmol; yield 18%) was isolated as a
white solid and the diacetate 11 (330 mg, 1.40 mmol; yield
22%) as a colorless liquid.] 1H NMR (300.1 MHz, C6D6): δ 1.36
(δZ), 3.02 (δX), 3.65 (δA(A′)), 4.42 (δK), and 4.44 (δL) [C(CHAHA′-
1
C-6, GeC6H4F), 164.2 (d, J CF ) 247.8 Hz, C-4, GeC6H4F). EI
MS: m/z 201 [78%, M+ - CH2OH], 109 [100%, C7H6F+]. Anal.
Calcd for C8H11FGeO2: C, 41.64; H, 4.80. Found: C, 41.3; H,
4.8.
3
3
OHZ)(CHKHLOAc)HX, J AX
+
3J A′X ) 12.2 Hz, J AZ
+
3J A′Z
)
2
3
3
11.4 Hz, J KL ) -11.0 Hz, J KX ) 6.6 Hz, J LX ) 6.9 Hz], 1.67
(s, 3 H, CCH3), 7.10-7.30 (m, 5 H, CC6H5). 13C NMR (75.5
MHz, C6D6): δ 20.3 (CCH3), 47.7 (CH), 63.9 (CCH2O), 65.1
(CCH2O), 127.2 (C-4, CC6H5), 128.4 (C-2/C-6, CC6H5), 128.8
(C-3/C-5, CC6H5), 139.9 (C-1, CC6H5), 170.7 (CdO). EI MS:
m/z 134 [27%, M+ - CH3COOH], 104 [100%, M+ - CH3COOH
- CH2O]. Anal. Calcd for C11H14O3: C, 68.02; H, 7.27.
Found: C, 68.3; H, 7.3.
2-P h en yl-1,3-p r op a n ed iol (7). Synthesis was according
to ref 7.
2-(4-F lu or op h en yl)-1,3-p r op a n ed iol (8). A solution of 20
(7.46 g, 37.6 mmol) in diethyl ether (50 mL) was added
dropwise at 0 °C over 1 h to a stirred suspension of lithium
aluminum hydride (3.57 g, 94.1 mmol) in diethyl ether (250
mL). The reaction mixture was heated under reflux for 6 h
and then stirred for a further 16 h at room temperature. After
the mixture was cooled to 0 °C, a saturated aqueous solution
of sodium sulfate was added cautiously in 10-mL portions until
a white coagulum was formed. The organic layer was decanted
and the coagulum extracted with diethyl ether (6 × 50 mL).
The combined organic extracts were dried over anhydrous
Na2SO4, and the solvent was removed under reduced pressure
(rotary evaporator). The crude product was purified by
distillation in vacuo (Vigreux column) to give 8 in 79% yield
as a colorless liquid (crystallization on cooling to room tem-
perature) (5.06 g, 29.7 mmol); bp 130 °C/0.01 Torr. 1H NMR
(400.1 MHz, C6D6): δ 2.99 (m, center, 1 H, CH), 3.78-3.94
[m, 4 H, C(CHAHBO)(CHA′HB′O)], 4.03 (s, 2 H, OH), 6.93-7.10
(m, 4 H, CC6H4F). 13C NMR (100.6 MHz, C6D6): δ 49.1 (CH),
r a c-2-(4-F lu or op h en yl)-3-h yd r oxyp r op yl Aceta te (r a c-
4). This compound was prepared analogously to the synthesis
of rac-1 by addition of acetic anhydride (2.40 g, 23.5 mmol)
and triethylamine (2.38 g, 23.5 mmol) to a solution of 8 (4.00
g, 23.5 mmol) in diethyl ether (250 mL). After column-
chromatographic separation on silica gel [eluent diethyl ether/
n-hexane (1:1, v/v); Rf(12) > Rf(rac-4) > Rf(8)], rac-4 was
isolated in 49% yield as a colorless liquid (2.44 g, 11.5 mmol).
[In addition, the diol 8 (408 mg, 2.40 mmol; yield 10%) was
isolated as a white solid and the diacetate 12 (1.24 g, 4.88
mmol; yield 21%) as a colorless liquid.] 1H NMR (400.1 MHz,
C6D6): δ 1.61 (δZ), 2.93 (δX), 3.58 (δA(A′)), 4.31 (δK), and 4.37
3
(δL) [C(CHAHA′OHZ)(CHKHLOAc)HX, J AX
+
3J A′X ) 12.0 Hz,
3J AZ + 3J A′Z ) 11.6 Hz, 2J KL ) -11.2 Hz, 3J KX ) 6.7 Hz, 3J LX
)
65.8 (CCH2O), 115.5 (d, J CF ) 21.1 Hz, C-3/C-5, CC6H4F),
2
6.8 Hz], 1.69 (s, 3 H, CCH3), 6.85-6.97 (m, 4 H, CC6H4F). 13C
NMR (100.6 MHz, C6D6): δ 20.3 (CCH3), 46.8 (CH), 63.7
129.8 (d, 3J CF ) 8.1 Hz, C-2/C-6, CC6H4F), 136.1 (d, 4J CF ) 3.6
Hz, C-1, CC6H4F), 162.2 (d, 1J CF ) 244.1 Hz, C-4, CC6H4F). EI
MS: m/z 170 [2%, M+], 122 [100%, M+ - CH2OH - OH]. Anal.
Calcd for C9H11FO2: C, 63.52; H, 6.51. Found: C, 63.1; H,
6.4.
2
(CCH2O), 65.0 (CCH2O), 115.8 (d, J CF ) 21.1 Hz, C-3/C-5,
3
CC6H4F), 130.2 (d, J CF ) 7.0 Hz, C-2/C-6, CC6H4F), 135.8 (d,
4J CF ) 3.0 Hz, C-1, CC6H4F), 162.3 (d, J CF ) 244.5 Hz, C-4,
1
CC6H4F), 170.5 (CdO). EI MS: m/z 212 [<1%, M+], 152 [33%,
M+ - CH3COOH], 122 [100%, M+ - CH3COOH - CH2O].
Anal. Calcd for C11H13FO3: C, 62.26; H, 6.17. Found: C, 61.7;
H, 6.1.
Bis(a cetoxym eth yl)p h en ylger m a n e (9). Acetic anhy-
dride (3.57 g, 35.0 mmol) and triethylamine (3.54 g, 35.0 mmol)
were added to a solution of 5 (3.20 g, 15.0 mmol) in diethyl
ether (150 mL). The mixture was heated under reflux for 8 h

1696 Organometallics, Vol. 17, No. 9, 1998
Tacke et al.
and then stirred for a further 12 h at room temperature. After
the organic layer was extracted with water (3 × 30 mL) and
dried over anhydrous Na2SO4, the solvent was removed under
reduced pressure (rotary evaporator) and the residue distilled
in vacuo (Vigreux column) to give 9 in 94% yield as a colorless
liquid (4.20 g, 14.1 mmol); bp 110 °C/0.01 Torr. 1H NMR (250.1
to a solution of 13 (22.9 g, 94.4 mmol) in diethyl ether (350
mL). The mixture of 16 and 17 was isolated by distillation as
a colorless liquid (22.8 g); bp 103-117 °C/0.01 Torr. This
mixture was used for the synthesis of 19 (see below).
Acetoxybis(acetoxym eth yl)ph en ylger m an e (18). A mix-
ture of 14 and 15 (22.8 g; see above) and sodium acetate (20.0
g, 244 mmol) in dimethylformamide (250 mL) was stirred at
80 °C for 8 h. The mixture was allowed to cool to room
temperature and the precipitate filtered off. The solvent of
the filtrate was removed under reduced pressure at room
temperature and diethyl ether (100 mL) added to the residue.
The resulting precipitate was filtered off and the solvent of
the filtrate removed under reduced pressure. The crude
product was purified by Kugelrohr distillation (oven temper-
ature 170 °C, 0.01 Torr) to give 18 in 65% yield (referred to
13) as a colorless liquid (21.0 g, 59.2 mmol). 1H NMR (250.1
MHz, C6D6): δ 1.65 [s, 6 H, COC(O)CH3], 1.98 [s, 3 H, GeOC-
3
MHz, C6D6): δ 1.71 (s, 6 H, CCH3), 4.40 (d, J HH ) 2.4 Hz, 4
H, GeCH2O), 5.04 (q, 3J HH ) 2.4 Hz, 1 H, GeH), 7.20-7.60 (m,
5 H, GeC6H5). 13C NMR (62.9 MHz, C6D6): δ 20.0 (CCH3),
55.1 (GeCH2O), 128.5 (C-3/C-5, GeC6H5), 129.5 (C-4, GeC6H5),
133.9 (C-1, GeC6H5), 135.0 (C-2/C-6, GeC6H5), 176.7 (CdO).
EI MS: m/z 297 [1%, M+ - H], 225 [100%, M+ - CH2OC(O)-
CH3]. Anal. Calcd for C12H16GeO4: C, 48.55; H, 5.43.
Found: C, 48.1; H, 5.4.
Bis(acetoxym eth yl)(4-flu or oph en yl)ger m an e (10). This
compound was prepared analogously to the synthesis of 9 by
addition of acetic anhydride (2.99 g, 29.3 mmol) and triethyl-
amine (2.96 g, 29.3 mmol) to a solution of 6 (2.91 g, 12.6 mmol)
in diethyl ether (100 mL). The crude product was purified by
distillation in vacuo (Vigreux column) to give 10 in 91% yield
as a colorless liquid (3.60 g, 11.4 mmol); bp 113 °C/0.01 Torr.
1H NMR (250.1 MHz, C6D6): δ 1.69 (s, 6 H, CCH3), 4.31 (d,
2
(O)CH3], 4.61 (δA) and 4.69 (δB) [Ge(CHAHBO)2, J AB ) -12.8
Hz], 7.2-8.0 (m, 5 H, GeC6H5). 13C NMR (62.9 MHz, C6D6):
δ 19.7 [COC(O)CH3], 21.8 [GeOC(O)CH3], 58.2 (GeCH2O),
128.4 (C-3/C-5, GeC6H5), 130.1 (C-4, GeC6H5), 134.2 (C-2/C-6,
GeC6H5), 135.5 (C-1, GeC6H5), 172.4 [GeOC(O)CH3], 174.2
3
3J HH ) 2.4 Hz, 4 H, GeCH2O), 4.96 (q, J HH ) 2.4 Hz, 1 H,
[COC(O)CH3]. EI MS: m/z 356 [1%, M+], 283 [100%, M+
-
GeH), 6.85-7.00 and 7.30-7.43 (m, 4 H, GeC6H4F). 13C NMR
(62.9 MHz, C6D6): δ 20.0 (CCH3), 55.2 (GeCH2O), 115.7 (d,
CH2OC(O)CH3]. Anal. Calcd for C14H18GeO6: C, 47.38; H,
5.11. Found: C, 47.1; H, 5.0.
4
2J CF ) 20.1 Hz, C-3/C-5, GeC6H4F), 129.3 (d, J CF ) 4.3 Hz,
3
Acet oxyb is(a cet oxym et h yl)(4-flu or op h en yl)ger m a n e
(19). This compound was prepared analogously to the syn-
thesis of 18 by treating a mixture of 16 and 17 (22.8 g; see
above) with sodium acetate (20.0 g, 244 mmol) in dimethyl-
formamide (250 mL). The crude product was purified by
Kugelrohr distillation (oven temperature 170 °C, 0.01 Torr)
to give 19 in 65% yield (referred to 13) as a colorless liquid
(22.9 g, 61.4 mmol). 1H NMR (250.1 MHz, C6D6): δ 1.63 [s, 6
H, COC(O)CH3], 1.96 [s, 3 H, GeOC(O)CH3], 4.51 (δA) and 4.65
C-1, GeC6H4F), 136.9 (d, J CF ) 8.2 Hz, C-2/C-6, GeC6H4F),
1
164.3 (d, J CF ) 248.4 Hz, C-4, GeC6H4F), 170.8 (CdO). EI
MS: m/z 315 [3%, M+ - H], 243 [100%, M+ - CH2OC(O)CH3].
Anal. Calcd for C12H15FGeO4: C, 45.78; H, 4.80. Found: C,
45.8; H, 4.8.
2-P h en yl-1,3-p r op a n ed iyl Dia ceta te (11). Synthesis was
according to ref 8.
2-(4-Flu or oph en yl)-1,3-pr opan ediyl Diacetate (12). This
compound was prepared analogously to the synthesis of 9 by
addition of acetic anhydride (4.91 g, 48.1 mmol) and triethyl-
amine (4.86 g, 48.0 mmol) to a solution of 8 (3.51 g, 20.6 mmol)
in diethyl ether (175 mL). The crude product was purified by
distillation in vacuo (Vigreux column) to give 12 in 95% yield
as a colorless liquid (5.00 g, 19.7 mmol); bp 110 °C/0.01 Torr.
1H NMR (400.1 MHz, C6D6): δ 1.70 (s, 6 H, CCH3), 3.15 (q,
3J HH ) 6.6 Hz, 1 H, CH), 4.25 (d, 3J HH ) 6.6 Hz, 4 H, CCH2O),
6.88 (δA(A′)) [CC6(HAHA′)2FX, 3J AX + 4J A′X ) 14.4 Hz]. 13C NMR
(100.6 MHz, C6D6): δ 20.2 (CCH3), 43.5 (CH), 64.7 (CCH2O),
2
(δB) [Ge(CHAHBO)2, J AB ) -12.5 Hz], 6.90-7.10 and 7.77-
7.90 (m, 4 H, GeC6H4F). 13C NMR (62.9 MHz, C6D6): δ 19.6
[COC(O)CH3], 21.8 [GeOC(O)CH3], 58.2 (GeCH2O), 115.6 (d,
4
2J CF ) 20.1 Hz, C-3/C-5, GeC6H4F), 130.9 (d, J CF ) 4.3 Hz,
3
C-1, GeC6H4F), 136.3 (d, J CF ) 7.3 Hz, C-2/C-6, GeC6H4F),
164.5 (d, 1J CF ) 249.0 Hz, C-4, GeC6H4F), 172.6 [COC(O)CH3],
174.3 [GeOC(O)CH3]. FI MS: m/z 374 [5%, M+], 301 [100%,
M+ - CH2OC(O)CH3]. Anal. Calcd for C14H17FGeO6: C, 45.10;
H, 4.60. Found: C, 44.6; H, 4.7.
2
3
115.6 (d, J CF ) 21.1 Hz, C-3/C-5, CC6H4F), 129.8 (d, J CF
)
(4-F lu or op h en yl)m a lon ic Acid (20). Synthesis was ac-
cording to ref 9.
4
8.1 Hz, C-2/C-6, CC6H4F), 134.6 (d, J CF ) 3.0 Hz, C-1,
1
CC6H4F), 162.4 (d, J CF ) 244.1 Hz, C-4, CC6H4F), 169.9
(S)-(Acet oxym et h yl)[((ter t-b u t yld ip h en ylsilyl)oxy)-
m eth yl]p h en ylger m a n e [(S)-21]. tert-Butylchlorodiphenyl-
silane (129 mg, 469 µmol) was added to a solution of (R)-1 (100
mg, 392 µmol; obtained by enzymatic transformation) and
imidazole (59 mg, 867 µmol) in dimethylformamide (4 mL),
and the reaction mixture was stirred at room temperature for
1 h. After the solvent was removed under reduced pressure,
diethyl ether (40 mL) was added. The mixture was extracted
with water (3 × 20 mL) and then dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure
and the residue purified by preparative layer chromatography
on silica gel [diethyl ether/n-hexane (1:3, v/v)] to give (S)-21
in 79% yield as a colorless liquid (153 mg, 310 µmol). 1H NMR
(400.1 MHz, C6D6): δ 1.24 [s, 9 H, C(CH3)3], 1.70 [s, C(O)CH3],
4.16 (δA(A′)), 4.47 (δK), 4.48 (δL), and 5.03 (δX) [Ge(CHAHA′O)-
(CdO). EI MS: m/z 194 [25%, M+ - CH3COOH], 43 [100%,
C(O)CH3+]. Anal. Calcd for C13H15FO4: C, 61.41; H, 5.95.
Found: C, 61.1; H, 5.8.
Dich lor obis(ch lor om eth yl)ger m a n e (13). Synthesis was
according to ref 4j.
Ch lor ob is(ch lor om et h yl)p h en ylger m a n e/Br om ob is-
(ch lor om eth yl)p h en ylger m a n e (14/15). A 2.1 M solution
of phenylmagnesium bromide in diethyl ether (43.2 mL, 90.7
mmol C6H5MgBr) was added dropwise at 0 °C over 2 h to a
stirred solution of 13 (22.0 g, 90.7 mmol) in diethyl ether (350
mL). After the reaction mixture was stirred at room temper-
ature for 4 h and heated under reflux for 4 h, the precipitate
was filtered off and the solvent of the filtrate removed under
reduced pressure. n-Pentane (100 mL) was added to the
residue and the resulting precipitate filtered off. The filtrate
was concentrated under reduced pressure and the residue
distilled in vacuo (Vigreux column) to give a mixture of 14 and
15 as a colorless liquid (22.8 g); bp 103-113 °C/0.01 Torr. This
mixture was used for the synthesis of 18 (see below).
Ch lor obis(ch lor om eth yl)(4-flu or oph en yl)ger m an e/Br o-
m obis(ch lor om eth yl)(4-flu or oph en yl)ger m an e (16/17). This
mixture was prepared analogously to the synthesis of 14/15
by addition of a 1.54 M solution of (4-fluorophenyl)magnesium
bromide in diethyl ether (61.3 mL, 94.4 mmol p-FC6H4MgBr)
3
3
2
3
(CHKHLO)HX, J AX + J A′X ) 4.6 Hz, J KL ) -12.5 Hz, J KX
)
3
2.4 Hz, J LX ) 2.8 Hz], 7.24-7.38, 7.60-7.67, and 7.81-7.90
(m, 15 H, GeC6H5, SiC6H5). 13C NMR (100.6 MHz, C6D6): δ
19.4 [C(CH3)3], 20.2 [C(O)CH3], 27.0 [C(CH3)3], 54.5 (GeCH2O),
55.1 (GeCH2O), 128.1 (C-3/C-5, SiC6H5), 128.5 (C-3/C-5, GeC6H5),
129.4 (C-4, GeC6H5), 129.98 (C-4, SiC6H5), 130.00 (C-4, SiC6H5),
133.56 (C-1, SiC6H5), 133.59 (C-1, SiC6H5), 134.7 (C-1, GeC6H5),
135.2 (C-2/C-6, GeC6H5), 136.1 (C-2/C-6, SiC6H5), 170.6 (CdO).
EI MS: m/z 493 [1%, M+ - H], 317 [100%, M+ - C6H5
-

Centrochiral Hydridogermanes
Organometallics, Vol. 17, No. 9, 1998 1697
20
366
C(CH3)3 - C(O)CH3]. Anal. Calcd for C26H32GeO3Si: C, 63.31;
Si: C, 74.96; H, 7.46. Found: C, 74.8; H, 7.6. [R] ) +28
20
H, 6.54. Found: C, 62.9; H, 6.5. [R] ) +25 (acetone, c )
(acetone, c ) 2.5).
366
2.5).
(R )-1-Ac e t o x y -3-((t er t -b u t y ld ip h e n y ls ily l)o x y )-2-
p h en ylp r op a n e [(R)-23]. This compound was prepared
analogously to the synthesis of (S)-21 by addition of tert-
butylchlorodiphenylsilane (177 mg, 644 µmol) to a solution of
(S)-3 (104 mg, 535 µmol; obtained by enzymatic transforma-
tion) and imidazole (80 mg, 1.18 mmol) in dimethylformamide
(4 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (R)-23 was isolated in 81%
yield as a colorless liquid (188 mg, 435 mmol). The NMR and
(R)-(Acet oxym et h yl)[((ter t-b u t yld ip h en ylsilyl)oxy)-
m eth yl]p h en ylger m a n e [(R)-21]. This compound was pre-
pared analogously to the synthesis of (S)-21 by addition of tert-
butylchlorodiphenylsilane (137 mg, 498 µmol) to a solution of
(S)-1 (106 mg, 416 µmol; obtained by enzymatic transforma-
tion) and imidazole (63 mg, 925 µmol) in dimethylformamide
(4 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (R)-21 was isolated in 81%
yield as a colorless liquid (167 mg, 339 µmol). The NMR and
MS data of the product were identical with those obtained for
20
366
MS data of the product were identical with those obtained for
(S)-23. [R] ) -25 (acetone, c ) 2.5).
20
366
(S)-21. [R] ) -23 (acetone, c ) 2.5).
(S)-1-Acetoxy-3-((ter t-bu tyld ip h en ylsilyl)oxy)-2-(4-flu -
or op h en yl)p r op a n e [(S)-24]. This compound was prepared
analogously to the synthesis of (S)-21 by addition of tert-
butylchlorodiphenylsilane (156 mg, 568 µmol) to a solution of
(R)-4 (100 mg, 471 µmol; obtained by enzymatic transforma-
tion) and imidazole (70 mg, 1.03 mmol) in dimethylformamide
(4 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (S)-24 was isolated in 81%
yield as a colorless liquid (172 mg, 382 µmol). 1H NMR (400.1
MHz, C6D6): δ 1.21 [s, 9 H, C(CH3)3], 1.70 [s, 3 H, C(O)CH3],
3.13 (δX), 3.88 (δA(A′)), 4.48 (δK), and 4.56 (δL) [C(CHAHA′O)-
(S)-(Acet oxym et h yl)[((ter t-b u t yld ip h en ylsilyl)oxy)-
m eth yl](4-flu or op h en yl)ger m a n e [(S)-22]. This compound
was prepared analogously to the synthesis of (S)-21 by addition
of tert-butylchlorodiphenylsilane (121 mg, 440 µmol) to a
solution of (R)-2 (100 mg, 367 µmol; obtained by enzymatic
transformation) and imidazole (55 mg, 808 µmol) in dimethyl-
formamide (4 mL). After preparative layer chromatography
on silica gel [diethyl ether/n-hexane (1:3, v/v)], (S)-22 was
isolated in 82% yield as a colorless liquid (154 mg, 301 µmol).
1H NMR (400.1 MHz, C6D6): δ 1.23 [s, 9 H, C(CH3)3] 1.70 [s,
3 H, C(O)CH3], 4.10 (δA), 4.11 (δB), 4.38 (δK), 4.40 (δL), and
(CHKHLO)HX, 3J AX + 3J A′X ) 11.6 Hz, 2J KL ) -11.0 Hz, 3J KX
7.0 Hz, J LX ) 6.7 Hz], 6.85-7.00, 7.28-7.36, and 7.70-7.89
(m, 14 H, CC6H4F, SiC6H5). 13C NMR (100.6 MHz, C6D6): δ
19.4 [C(CH3)3], 20.3 [C(O)CH3], 27.0 [C(CH3)3)], 46.6 (CH), 64.6
)
2
3
3
4.95 (δX) [Ge(CHAHBO)(CHKHLO)HX, J AB ) -11.7 Hz, J AX
)
)
3
2
3
3
2.1 Hz, J BX ) 2.5 Hz, J KL ) -12.3 Hz, J KX ) 2.4 Hz, J LX
2.7 Hz], 6.90-7.00, 7.30-7.46, and 7.78-7.87 (m, 14 H,
GeC6H4F, SiC6H5). 13C NMR (100.6 MHz, C6D6): δ 19.4
[C(CH3)3], 20.1 [C(O)CH3], 27.0 [C(CH3)3], 54.4 (GeCH2O), 55.0
(GeCH2O), 115.6 (d, 2J CF ) 19.6 Hz, C-3/C-5, GeC6H4F), 128.1
(C-3/C-5, SiC6H5), 129.9 (d, 4J CF ) 3.6 Hz, C-1, GeC6H4F), 130.1
(C-4, SiC6H5), 133.46 (C-1, SiC6H5), 133.48 (C-1, SiC6H5),
136.03 (C-2/C-6, SiC6H5), 136.05 (C-2/C-6, SiC6H5), 137.1 (d,
2
(CCH2O), 65.3 (CCH2O), 115.3 (d, J CF ) 20.8 Hz, C-3/C-5,
CC6H4F), 128.1 (C-3/C-5, SiC6H5), 130.0 (C-4, SiC6H5), 130.1
(d, 3J CF ) 5.5 Hz, C-2/C-6, CC6H4F), 133.6 (C-1, SiC6H5), 135.3
(C-1, CC6H4F), 135.87 (C-2/C-6, SiC6H5), 135.96 (C-2/C-6,
SiC6H5), 162.3 (d, 1J CF ) 244.8 Hz, C-4, CC6H4F), 170.0 (CdO).
CI MS (positive ions): m/z 451 [100%, (M + H)+]. Anal. Calcd
1
3J CF ) 7.3 Hz, C-2/C-6, GeC6H4F), 162.8 (d, J CF ) 247.5 Hz,
for C27H31FO3Si: C, 71.97; H, 6.93. Found: C, 72.7; H, 7.1.
20
C-4, GeC6H4F), 170.6 (CdO). CI MS (positive ions): m/z 511
[R] ) +23 (acetone, c ) 2.5).
366
[40%, (M - H)+], 417 [100%, (M - C6H4F)+]. Anal. Calcd for
(R)-1-Acetoxy-3-((ter t-bu tyld ip h en ylsilyl)oxy)-2-(4-flu -
or op h en yl)p r op a n e [(R)-24]. This compound was prepared
analogously to the synthesis of (S)-21 by addition of tert-
butylchlorodiphenylsilane (156 mg, 568 µmol) to a solution of
(S)-4 (100 mg, 471 µmol; obtained by enzymatic transforma-
tion) and imidazole (70 mg, 1.03 mmol) in dimethylformamide
(4 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (R)-24 was isolated in 85%
yield as a colorless liquid (180 mg, 399 µmol). The NMR and
C
26H31FGeO3Si: C, 61.09; H, 6.11. Found: C, 61.3; H, 6.4.
20
[R] ) +22 (acetone, c ) 2.5).
366
(R)-(Acet oxym et h yl)[((ter t-b u t yld ip h en ylsilyl)oxy)-
m eth yl](4-flu or op h en yl)ger m a n e [(R)-22]. This compound
was prepared analogously to the synthesis of (S)-21 by addition
of tert-butylchlorodiphenylsilane (121 mg, 440 µmol) to a
solution of (S)-2 (100 mg, 367 µmol; obtained by enzymatic
transformation) and imidazole (55 mg, 808 µmol) in dimethyl-
formamide (4 mL). After preparative layer chromatography
on silica gel [diethyl ether/n-hexane (1:3, v/v)], (R)-22 was
isolated in 78% yield as a colorless liquid (146 mg, 286 µmol).
MS data of the product were identical with those obtained for
20
366
(S)-24. [R] ) -22 (acetone, c ) 2.5).
(S )-[((t e r t -B u t y l d i p h e n y l s i l y l )o x y )m e t h y l ](h y -
d r oxym eth yl)p h en ylger m a n e [(S)-25]. Potassium carbon-
ate (109 mg, 789 µmol) was added to a solution of (S)-21 (97
mg, 197 µmol; for synthesis, see above) in methanol (3 mL).
After the reaction mixture was stirred at room temperature
for 1 h, diethyl ether (40 mL) was added and the organic layer
was extracted with water (3 × 20 mL) and then dried over
anhydrous Na2SO4. The solvent was removed under reduced
pressure (rotary evaporator) and the residue purified by
preparative layer chromatography on silica gel [diethyl ether/
n-hexane (1:3, v/v)] to give (S)-25 in 85% yield as a colorless
liquid (75 mg, 166 µmol). 1H NMR (400.1 MHz, C6D6): δ 1.24
[s, 9 H, C(CH3)3], 1.5 (br s, 1 H, OH), 4.11 (δA(A′)), 4.16 (δB),
4.19 (δC), and 4.89 (δX) [Ge(CHAHA′O)(CHBHCO)HX, 3J AX + 3J A′X
) 5.2 Hz, 2J BC ) -11.6 Hz, 3J BX ) 3.1 Hz, 3J CX ) 1.6 Hz], 7.22-
7.40, 7.60-7.67, and 7.80-7.90 (m, 15 H, GeC6H5, SiC6H5).
13C NMR (100.6 MHz, C6D6): δ 19.4 [C(CH3)3], 27.0 [C(CH3)3],
53.4 (GeCH2O), 56.6 (GeCH2O), 128.09 (C-3/C-5, SiC6H5),
128.12 (C-3/C-5, SiC6H5), 128.5 (C-3/C-5, GeC6H5), 129.3 (C-
4, GeC6H5), 130.01 (C-4, SiC6H5), 130.05 (C-4, SiC6H5), 133.35
(C-1, SiC6H5), 133.37 (C-1, SiC6H5), 135.2 (C-2/C-6, GeC6H5),
135.5 (C-1, GeC6H5), 136.06 (C-2/C-6, SiC6H5), 136.07 (C-2/C-
6, SiC6H5). CI MS (positive ions): m/z 453 [5%, (M + H)+],
The NMR and MS data of the product were identical with
20
those obtained for (S)-22. [R] ) -24 (acetone, c ) 2.5).
366
(S )-1-Ac e t o x y -3-((t er t -b u t y ld ip h e n y ls ily l)o x y )-2-
p h en ylp r op a n e [(S)-23]. This compound was prepared
analogously to the synthesis of (S)-21 by addition of tert-
butylchlorodiphenylsilane (170 mg, 618 µmol) to a solution of
(R)-3 (100 mg, 515 µmol; obtained by enzymatic transforma-
tion) and imidazole (78 mg, 1.15 mmol) in dimethylformamide
(4 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (S)-23 was isolated in 81%
yield as a colorless liquid (180 mg, 416 µmol). 1H NMR (400.1
MHz, C6D6): δ 1.24 [s, 9 H, C(CH3)3], 1.68 [s, 3 H, C(O)CH3],
3.25 (δX), 3.97 (δA(A′)), 4.60 (δK), and 4.67 (δL) [C(CHAHA′O)-
(CHKHLO)HX, 3J AX + 3J A′X ) 11.6 Hz, 2J KL ) -10.9 Hz, 3J KX
)
3
7.4 Hz, J LX ) 6.6 Hz], 7.14-7.37 and 7.70-7.82 (m, 15 H,
CC6H5, SiC6H5). 13C NMR (100.6 MHz, C6D6): δ 19.4 [C(CH3)3],
20.4 [C(O)CH3], 27.0 [C(CH3)3], 47.5 (CH), 64.7 (CCH2O), 65.5
(CCH2O), 127.1 (C-4, CC6H5), 128.1 (C-3/C-5, SiC6H5), 128.6
(C-2/C-6, CC6H5), 129.9 (C-4, SiC6H5), 130.0 (C-3/C-5, CC6H5),
133.8 (C-1, SiC6H5), 135.94 (C-2/C-6, SiC6H5), 136.0 (C-2/C-6,
SiC6H5), 140.2 (C-1, CC6H5), 170.0 (CdO). CI MS (positive
ions): m/z 433 [100%, (M + H)+]. Anal. Calcd for C27H32O3-

1698 Organometallics, Vol. 17, No. 9, 1998
Tacke et al.
297 [100%]. Anal. Calcd for C24H30GeO2Si: C, 63.89; H, 6.70.
synthesis, see above) in methanol (3 mL). After preparative
layer chromatography on silica gel [diethyl ether/n-hexane (1:
3, v/v)], (R)-27 was isolated in 85% yield as a colorless liquid
20
Found: C, 64.2; H, 6.7. [R] ) +28 (acetone, c ) 2.5).
366
(R)-[((ter t-Bu t yld ip h en ylsilyl)oxy)m et h yl](h yd r oxy-
m eth yl)p h en ylger m a n e [(R)-25]. This compound was pre-
pared analogously to the synthesis of (S)-25 by addition of
potassium carbonate (134 mg, 970 µmol) to a solution of (R)-
21 (120 mg, 243 µmol; for synthesis, see above) in methanol
(3 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (R)-25 was isolated in 87%
yield as a colorless liquid (95 mg, 211 µmol). The NMR and
(85 mg, 218 µmol). The NMR and MS data of the product were
20
366
identical with those obtained for (S)-27. [R]
tone, c ) 2.5).
) -14 (ace-
(S)-3-((ter t-Bu tyld ip h en ylsilyl)oxy)-2-(4-flu or op h en yl)-
1-p r op a n ol [(S)-28]. This compound was prepared analo-
gously to the synthesis of (S)-25 by addition of potassium
carbonate (158 mg, 1.14 mmol) to a solution of (S)-24 (129 mg,
286 µmol; for synthesis, see above) in methanol (3 mL). After
preparative layer chromatography on silica gel [diethyl ether/
n-hexane (1:3, v/v)], (S)-28 was isolated in 79% yield as a
colorless liquid (92 mg, 225 µmol). 1H NMR (400.1 MHz,
C6D6): δ 1.23 [s, 9 H, C(CH3)3], 1.76 (s, 1 H, OH), 2.99 (δX),
3.83 (δA), 3.93 (δB), 3.94 (δC), and 4.01 (δD) [C(CHAHBO)-
MS data of the product were identical with those obtained for
20
366
(S)-25. [R] ) -25 (acetone, c ) 2.5).
(S)-[((ter t-Bu t yld ip h en ylsilyl)oxy)m et h yl](4-flu or o-
p h en yl)(h yd r oxym eth yl)ger m a n e [(S)-26]. This compound
was prepared analogously to the synthesis of (S)-25 by addition
of potassium carbonate (108 mg, 781 µmol) to a solution of
(S)-22 (100 mg, 196 µmol; for synthesis, see above) in methanol
(3 mL). After preparative layer chromatography on silica gel
[diethyl ether/n-hexane (1:3, v/v)], (S)-26 was isolated in 84%
yield as a colorless liquid (77 mg, 164 µmol). 1H NMR (400.1
MHz, C6D6): δ 1.23 [s, 9 H, C(CH3)3], 1.5 (br s, 1 H, OH), 4.01
(δA), 4.05 (δB), 4.09 (δC), 4.13 (δD), and 4.81 (δX) [Ge(CHAHBO)-
2
3
3
(CHCHDO)HX, J AB ) -10.7 Hz, J AX ) 5.8 Hz, J BX ) 6.7 Hz,
2J CD ) -10.0 Hz, J CX ) 5.5 Hz, J DX ) 7.1 Hz], 6.80-7.00,
7.28-7.37, and 7.75-7.81 (m, 14 H, CC6H4F, SiC6H5). 13C
NMR (100.6 MHz, C6D6): δ 19.3 [C(CH3)3], 27.0 [C(CH3)3], 49.7
3
3
2
(CH), 64.5 (CCH2O), 66.4 (CCH2O), 115.3 (d, J CF ) 21.5 Hz,
C-3/C-5, CC6H4F), 128.1 (C-3/C-5, SiC6H5), 130.0 (C-4, SiC6H5),
130.1 (d, 3J CF ) 4.9 Hz, C-2/C-6, CC6H4F), 133.60 (C-1, SiC6H5),
133.65 (C-1, SiC6H5), 135.91 (C-2/C-6, SiC6H5), 135.95 (C-2/
2
3
3
(CHCHDO)HX, J AB ) -12.1 Hz, J AX ) 2.5 Hz, J BX ) 1.8 Hz,
2J CD ) -11.8 Hz, J CX ) 2.8 Hz, J DX ) 1.7 Hz], 6.90-7.00,
7.28-7.45, and 7.77-7.89 (m, 14 H, GeC6H4F, SiC6H5). 13C
NMR (100.6 MHz, C6D6): δ 19.4 [C(CH3)3], 27.0 [C(CH3)3], 53.3
(GeCH2O), 55.5 (GeCH2O), 115.6 (d, J CF ) 19.6 Hz, C-3/C-5,
GeC6H4F), 128.11 (C-3/C-5, SiC6H5), 128.13 (C-3/C-5, SiC6H5),
3
3
4
C-6, SiC6H5), 136.4 (d, J CF ) 3.5 Hz, C-1, CC6H4F), 162.2 (d,
1J CF ) 244.1 Hz, C-4, CC6H4F). CI MS (positive ions): m/z
409 [100%, (M + H)+]. Anal. Calcd for C25H29FO2Si: C, 73.49;
2
20
366
H, 7.15. Found: C, 73.7; H, 7.3. [R] ) +18 (acetone, c )
4
130.09 (C-4, SiC6H5), 130.12 (C-4, SiC6H5), 130.7 (d, J CF
)
2.5).
3.6 Hz, C-1, GeC6H4F), 133.28 (C-1, SiC6H5), 133.31 (C-1,
SiC6H5), 136.02 (C-2/C-6, SiC6H5), 136.05 (C-2/C-6, SiC6H5),
(R)-3-((ter t-Bu tyld ip h en ylsilyl)oxy)-2-(4-flu or op h en yl)-
1-p r op a n ol [(R)-28]. This compound was prepared analo-
gously to the synthesis of (S)-25 by addition of potassium
carbonate (211 mg, 1.53 mmol) to a solution of (R)-24 (172 mg,
382 µmol; for synthesis, see above) in methanol (4 mL). After
preparative layer chromatography on silica gel [diethyl ether/
n-hexane (1:3, v/v)], (R)-28 was isolated in 76% yield as a
colorless liquid (119 mg, 291 µmol). The NMR and MS data
3
1
137.0 (d, J CF ) 7.3 Hz, C-2/C-6, GeC6H4F), 164.2 (d, J CF
)
-
247.1 Hz, C-4, GeC6H4F). EI MS: m/z 439 [18%, M+
CH2OH], 317 [100%, C14H15GeO2Si+]. Anal. Calcd for
C
24H29FGeO2Si: C, 61.44; H, 6.23. Found: C, 61.2; H, 6.3.
20
[R] ) +24 (acetone, c ) 2.5).
366
(R)-[((ter t-Bu t yld ip h en ylsilyl)oxy)m et h yl](4-flu or o-
p h en yl)(h yd r oxym et h yl)ger m a n e [(R)-26]. This com-
pound was prepared analogously to the synthesis of (S)-25 by
addition of potassium carbonate (130 mg, 941 µmol) to a
solution of (R)-22 (120 mg, 235 µmol; for synthesis, see above)
in methanol (3 mL). After preparative layer chromatography
on silica gel [diethyl ether/n-hexane (1:3, v/v)], (R)-26 was
isolated in 84% yield as a colorless liquid (92 mg, 196 µmol).
of the product were identical with those obtained for (S)-28.
20
[R] ) -17 (acetone, c ) 2.5).
366
P r ep a r a tion of th e MTP A Ester s 29a /29b-32a /32b
(Gen er a l P r oced u r e). (S)-R-Methoxy-R-(trifluoromethyl)-
phenylacetyl chloride [(S)-MTPA-Cl; prepared from (R)-R-
methoxy-R-(trifluoromethyl)phenylacetic acid (Fluka, 65364)
as described in ref 12] (56 µL) was added at room temperature
to a stirred solution of the respective monohydroxy compounds
1-4 (140 µmol) in toluene/pyridine (2:1, v/v) (1.2 mL). After
the mixture was stirred at room temperature for 12 h
[complete conversion as monitored by TLC; silica gel plates
(Merck, 5554), n-hexane/diethyl ether (2:1, v/v), UV detection],
3-(dimethylamino)-1-propylamine (60 µL) was added and the
mixture stirred for 10 min. After addition of diethyl ether (15
mL) and 2 M hydrochloric acid (10 mL), the organic layer was
separated and shaken first with a saturated aqueous Na2CO3
solution (10 mL) and then with a saturated aqueous NaCl
solution (10 mL). The organic layer was dried over MgSO4,
the solvent removed under reduced pressure (rotary evapora-
tor), and the residue dissolved in C6D6 (0.5 mL). To remove
traces of diethyl ether, the solvent was again evaporated and
the residue dissolved in C6D6. The sample obtained by this
procedure was used for the NMR-spectroscopic studies (de-
termination of the ee values of the enantiomers of 1-4 by
integration of characteristic resonance signals of the respective
diastereomeric MTPA esters). For NMR data, see the Sup-
porting Information.
The NMR and MS data of the product were identical with
20
366
those obtained for (S)-26. [R] ) -26 (acetone, c ) 2.5).
(S)-3-((ter t-Bu t yld ip h e n ylsilyl)oxy)-2-p h e n yl-1-p r o-
p a n ol [(S)-27]. This compound was prepared analogously to
the synthesis of (S)-25 by addition of potassium carbonate (140
mg, 1.01 mmol) to a solution of (S)-23 (110 mg, 254 µmol; for
synthesis, see above) in methanol (3 mL). After preparative
layer chromatography on silica gel [diethyl ether/n-hexane (1:
3, v/v)], (S)-27 was isolated in 83% yield as a colorless liquid
(82 mg, 210 µmol). 1H NMR (400.1 MHz, C6D6): δ 1.24 [s, 9
H, C(CH3)3], 1.7 (br s, 1 H, OH), 3.10 (δX), 3.94 (δA), 4.03 (δC),
4.04 (δB), and 4.10 (δD) [C(CHAHBO)(CHCHDO)HX, 2J AB ) -10.7
3
3
2
3
Hz, J AX ) 5.8 Hz, J BX ) 6.8 Hz, J CD ) -10.0 Hz, J CX ) 5.5
3
Hz, J DX ) 7.4 Hz], 7.10-7.24, 7.28-7.35, and 7.76-7.83 (m,
15 H, CC6H5, SiC6H5). 13C NMR (100.6 MHz, C6D6): δ 19.4
[C(CH3)3], 27.0 [C(CH3)3] 50.7 (CH), 64.8 (CCH2O), 66.7
(CCH2O), 127.0 (C-4, CC6H5), 128.1 (C-3/C-5, SiC6H5), 128.6
(C-2/C-6, CC6H5), 129.98 (C-4, SiC6H5), 130.0 (C-3/C-5, CC6H5),
133.7 (C-1, SiC6H5), 133.8 (C-1, SiC6H5), 135.96 (C-2/C-6,
SiC6H5), 135.99 (C-2/C-6, SiC6H5), 140.7 (C-1, CC6H5). CI MS
(positive ions): m/z 391 [100%, (M + H)+]. Anal. Calcd for
P r ep a r a tion of th e MTP A Ester s 33a /33b. The MTPA
esters 33a /33b were prepared analogously to the synthesis of
the MTPA esters 29a /29b-32a /32b. For NMR data, see the
Supporting Information.
C
25H30O2Si: C, 76.88; H, 7.74. Found: C, 77.0; H, 7.7.
20
[R] ) +15 (acetone, c ) 2.5).
366
(R)-3-((ter t-Bu t yld ip h en ylsilyl)oxy)-2-p h en yl-1-p r o-
p a n ol [(R)-27]. This compound was prepared analogously to
the synthesis of (S)-25 by addition of potassium carbonate (142
mg, 1.03 mmol) to a solution of (R)-23 (111 mg, 257 µmol; for
(12) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34,
2543-2549.

Centrochiral Hydridogermanes
Organometallics, Vol. 17, No. 9, 1998 1699
Deter m in a tion of th e En a n tiom er ic P u r ities of th e
An tip od es of 1-4 by Liqu id Ch r om a togr a p h y. The (R)-
and (S)-enantiomers of 1-4 were separated by liquid chroma-
tography on cellulose tribenzoate (10-20 µm; Riedel-deHae¨n,
39852). The experimental conditions were as follows: HPLC
pump, Shimadzu LC6-A; detector, Soma S-3702 UV-VIS;
integrator, Shimadzu C-R3A; column (10 mm i.d. × 150 mm),
Merck Superformance; eluent, n-hexane/2-propanol (95:5, v/v)
(1), n-hexane/diisopropyl ether (50:50, v/v) (2), n-hexane/
ethanol (90:10, v/v) (3), or n-hexane/tert-butyl methyl ether (50:
50, v/v) (4) (HPLC-grade solvents purchased from Merck);
detection, 215 nm; T, ambient temperature; injection volume,
20 µL (10 mg of the sample material dissolved in 1 mL of the
eluent). The retention times of the antipodes of 1-4 are listed
in Table 3. For typical chromatograms, see the Supporting
Information.
Der iva tiza tion of 2 for th e GC Stu d ies. Pyridine (150
µL) and N-methylbis(trifluoroacet)amide (MBTFA) (150 µL)
were added to a 4-mg sample of 2 and the mixture was kept
at room temperature for 30 min. After the excess pyridine
and MBTFA were blown off with a stream of nitrogen, the
residue was dissolved in toluene (150 µL) and a 0.5-µL sample
of this solution injected into the gas chromatograph.
Der iva tiza tion of 4 for th e GC Stu d ies. A 4-mg sample
of 4 was treated with pyridine (100 µL) and trifluoroacetic
anhydride (100 µL) under the same conditions as described
for the derivatization of 2. For typical chromatograms, see
the Supporting Information.
Ack n ow led gm en t . We thank the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen
Industrie for financial support and the Bayer AG
(Leverkusen and Wuppertal-Elberfeld, Germany) and
Merck KGaA (Darmstadt, Germany) for support with
chemicals.
Deter m in a tion of th e En a n tiom er ic P u r ities of th e
An tip od es of 2 a n d 4 by Ca p illa r y Ga s Ch r om a togr a p h y.
The (R)- and (S)-enantiomers of 2 and 4 were separated, after
transformation into the corresponding trifluoroacetates, by
capillary gas chromatography [gas chromatograph, HP 6890;
Lipodex E column (0.25 mm i.d. × 23 m, film thickness 0.15
µm), Chrompack; carrier gas, hydrogen; temperature program,
50 °C (1 min) to 200 °C (10 min) with 3 °C/min; injector
temperature, 180 °C; split, 1:80; detector, FID; detector
temperature, 250 °C]. The retention times of the antipodes
of 2 and 4 are listed in Table 4.
Su p p or tin g In for m a tion Ava ila ble: NMR data for the
MTPA esters 29a /29b-33a /33b and chromatograms obtained
for the analytical liquid-chromatographic (HPLC) and gas-
chromatographic separation of the (R)- and (S)-enantiomers
of 2 (4 pages). Ordering information is given on any current
masthead page.
OM971025I