The first isolable 1,1-dilithiogermane and its unusual dimeric structure - An effective reagent for the preparation of double-bonded derivatives of group 14 elements

Article abstract of DOI:10.1002/1521-3773(20020503)41:9<1598::AID-ANIE1598>3.0.CO;2-8

1,1-Dilithiogermanes 1a and 1b were obtained by treatment of the persilylsubstituted germacyclopropenes with lithium, which cleaved the two Ge-C bonds in the three-membered ring. The structure of 1b has been confirmed by X-ray crystallography and shows a

Full text of DOI:10.1002/1521-3773(20020503)41:9<1598::AID-ANIE1598>3.0.CO;2-8

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R3Si
SiR3
The First Isolable 1,1-Dilithiogermane and Its
Unusual Dimeric Structure–An Effective
Reagent for the Preparation of Double-Bonded
Derivatives of Group 14 Elements**
R3Si
Cl
SiR3
Cl
Ge
K /
Me3Si
reflux
SiMe3
Ge
Me3Si
SiMe3
1
2
Akira Sekiguchi,* Rika Izumi, Shinji Ihara,
Masaaki Ichinohe, and Vladimir Ya. Lee
a: R3Si = iPr3Si, b: R3Si = tBu2MeSi
R3Si
Li
SiR3
Organolithium derivatives are among the most important
organometallic compounds in organic chemistry.[1] The orga-
nolithium compounds are well investigated, however, our
knowledge of lithium derivatives of heavier Group 14 ele-
ments is still very limited. Among the most intensively studied
are silyllithium compounds,[2] whereas very little experimental
work on germyllithium derivatives has been published.[3]
1,1-Dilithiogermane derivatives (R2GeLi2) are of interest in
view of their synthetic utility, structure, and reactivity.
However, there are few reports of dilithiogermane com-
pounds, because of the lack of a useful synthetic method.[4] In
1999, we reported the unexpected reaction of silacyclopro-
pene with lithium to form a dilithiosilane derivative.[5] As part
of this study, we have examined the reaction of the persilyl-
substituted germacyclopropene with lithium and have found
the clean formation of [R2GeLi2] and bis(trimethylsilyl)ace-
Li
Ge
+
Me3Si
SiMe3
Et2O / THF
Li
3
Scheme 1. Synthesis of germacyclopropenes and dilithiogermanes.
were determined by X-ray analysis and show isosceles-
triangle cores with the shortest endocyclic C C double bond
lengths of all germacyclopropenes known to date: 1.317(3) ä
for 2a and 1.317(2) ä for 2b.[6,7]
ˆ
The reduction of both germacyclopropenes 2 with excess
lithium in diethyl ether/tetrahydrofuran at room temperature
quickly produced a red-brown reaction mixture containing
the desired bis(triisopropylsilyl)dilithiogermane (3a) and
bis(di-tert-butyl(methyl)silyl)dilithiogermane (3b). After the
removal of lithium, the solvent, and the bis(trimethylsilyl)-
acetylene, the oily residue was washed with dry pentane to
give 1,1-dilithiogermanes 3a and 3b as extremely air- and
moisture-sensitive pale yellow powders (Scheme 1). Such 1,1-
dilithiogermane derivatives 3 have been isolated as stable
compounds for the first time, although the formation of 1,1-
dilithiogermanes was proposed some time ago.[4]
À
tylene by cleavage of the two Ge C bonds in the three-
membered ring. We herein report the synthesis and isolation
of the first stable 1,1-dilithiogermane derivative, its unexpect-
ed crystal structure, and its use in the preparation of double-
bonded derivatives of heavier Group 14 elements.
As a precursor for 1,1-dilithiogermane, we first prepared
germacyclopropenes, from which the generation of the 1,1-di-
lithiogermane was expected upon reduction with lithium. To
date, only six examples of stable germacyclopropenes have
been described,[6] with five of them being structurally
characterized. We employed a new method for the prepara-
tion of germacyclopropenes, in which the germylene was
generated in situ by reduction of the corresponding dichloro-
germane 1 with molten potassium, in the presence of
bis(trimethylsilyl)acetylene, without solvent (Scheme 1). Af-
ter 19 h under reflux, the starting chlorogermanes 1a and 1b
were completely consumed and the corresponding germacy-
clopropenes, 1,1-bis(triisopropylsilyl)-2,3-bis(trimethylsilyl)-
1-germacycloprop-2-ene (2a; 83%) and 1,1-bis(di-tert-butyl-
(methyl)silyl)-2,3-bis(trimethylsilyl)-1-germacycloprop-2-ene
(2b; 81%), were formed. The germacyclopropenes 2a and 2b
were isolated by recrystallization from pentane as air-stable
colorless crystals. The crystal structures of both 2a and 2b
The crystal structure of 3b was determined by X-ray
diffraction analysis (Figure 1).[7] This structure is rather
[*] Prof. Dr. A. Sekiguchi, Dipl.-Chem. R. Izumi, Dipl.-Chem. S. Ihara,
Dr. M. Ichinohe, Dr. V. Ya. Lee
Figure 1. Structure of 3b (ORTEP plot, thermal ellipsoids set at the 30%
level; hydrogen atoms omitted for clarity). Selected interatomic distance-
s [ä] and angles [8]: Ge(1)-Si(1) 2.4026(11), Ge(1)-Si(2) 2.4145(10), Ge(1)-
Li(1) 2.664(6), Ge(1)-Li(2) 2.649(6), Li(1) ¥¥¥ O(1) 2.092(6), Li(2)' ¥¥¥ O(1)
2.041(7), Li(2) ¥¥¥ O(2) 1.955(6), Li(2) ¥¥¥ O(1)' 2.041(7); Si(1)-Ge(1)-Si(2)
109.42(4), Si(1)-Ge(1)-Li(2) 88.61(14), Si(2)-Ge(1)-Li(2) 101.18(15), Si(1)-
Ge(1)-Li(1) 104.94(15), Si(2)-Ge(1)-Li(1) 125.81(14), Li(2)-Ge(1)-Li(1)
120.46(19), Si(1)-Ge(1)-Li(1)' 122.52(14), Si(2)-Ge(1)-Li(1)' 123.96(14),
Li(2)-Ge(1)-Li(1)' 63.23(18), Li(1)-Ge(1)-Li(1)' 60.8(2), Ge(1)-Li(1)-
Ge(1)' 119.2(2).
Department of Chemistry
University of Tsukuba
Tsukuba, Ibaraki 305-8571 (Japan)
Fax : (‡81)298-53-4314
E-mail: sekiguch@staff.chem.tsukuba.ac.jp
[**] This work was supported by Grant-in-Aid for Scientific Research
(Nos. 12042213, 13440185, 13029015) from the Ministry of Education,
Science and Culture of Japan, and TARA (Tsukuba Advanced
Research Alliance) Fund.
1598
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1433-7851/02/4109-1598 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 9

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13C{1H} NMR (75.5 MHz, [D8]THF, TMS): d ˆ À1.4, 21.9, 26.5; 29Si{1H}
NMR (59.6 MHz, [D8]THF, TMS): d ˆ 24.0.
unusual and shows a dimeric molecule, in which the two
lithium atoms Li(1) and Li(1)' are shared by the two
Ge atoms, to form an almost regular rhombus Ge(1)-Li(1)-
1
Spectral data for 3a: H NMR (300 MHz, [D8]THF, TMS): d ˆ 0.80 1.08
(m, 6H), 1.09 (d, J ˆ 7.7 Hz, 36H), 13C{1H} NMR (75.5 MHz, [D8]THF,
TMS): d ˆ 17.0, 22.1; 29Si{1H} NMR (59.6 MHz, [D8]THF, TMS): d ˆ 31.1.
Ge(1)'-Li(1)'
(Ge(1)-Li(1) ˆ 2.664(6),
Ge(1)-Li(1)' ˆ
2.709(6) ä). This arrangement is in sharp contrast to that of
the monomeric and symmetrical 1,1-dilithiosilane.[5] The
geometry of the Ge atom in 3b is far from the ideal
tetrahedral: both Ge atoms are pentacoordinated and bound
to the three Li atoms (Li(1), Li(1)', and Li(2) for Ge(1); Li(1),
Li(1)', and Li(2)' for Ge(1)'). Both Li(1) and Li(1)' atoms have
one coordinated THF molecule, whereas each Li(2) and Li(2)'
Received: November 19, 2001 [Z18236]
[1] For monographs on organolithium chemistry, see: a) B. J. Wakefield,
Organolithium Methods, Academic Press, London, 1988; b) A.-M.
Sapse, P. v. R. Schleyer, Lithium Chemistry:
Experimental Overview, Wiley, New York, 1995.
A Theoretical and
À
atom is coordinated by two THF molecules. The Si Ge bond
[2] For reviews on silyllithium compounds, see: a) P. D. Lickiss, C. M.
Smith, Coord. Chem. Rev. 1995, 145, 75; b) K. Tamao, A. Kawachi,
Adv. Organomet. Chem. 1995, 38, 1; c) J. Belzner, U. Dehnert, The
Chemistryof Organic Silicon Compounds , Vol. 2, Part 1 (Eds.: Z.
Rappoport, Y. Apeloig), Wi1ey, Chichester, 1998, chap. 14; d) A.
Sekiguchi, V. Ya. Lee, M. Nanjo, Coord. Chem. Rev. 2000, 210, 11.
[3] For recent papers on germyllithium compounds, see: a) J.-H. Hong, Y.
Pan, P. Boudjouk, Angew. Chem. 1996, 108, 213; Angew. Chem. Int.
Ed. Engl. 1996, 35, 186; b) R. West, H. Sohn, D. R. Powell, T. M¸ller,
Y. Apeloig, Angew. Chem. 1996, 108, 1095; Angew. Chem. Int. Ed.
Engl. 1996, 35, 1002; c) S.-B. Choi, P. Boudjouk, J.-H. Hong, Organo-
metallics 1999, 18, 2919; d) A. Kawachi, Y. Tanaka, K. Tamao, Eur. J.
Inorg. Chem. 1999, 461; e) S.-B. Choi, P. Boudjouk, K. Qin, Organo-
metallics 2000, 19, 1806.
À
lengths of 2.4026(11) and 2.4145(10) ä, as well as the Ge Li
bond lengths of 2.664(6), 2.649(6), and 2.709(6) ä, lie in the
normal range (2.38 2.46 ä for Si Ge bond lengths, and
[8]
À
[3d]
À
2.61 2.76 ä for Ge Li bond lengths).
As we expected, the 1,1-dilithiogermanes 3 are highly
reactive. The most important examples of the reactivity of 3
are their coupling reactions with dihalogermane or dihalosi-
lane to form the corresponding digermene or germasilene.
Thus, the reaction of 3a with dichlorobis(triisopropylsilyl)-
germane cleanly gave the tetrakis(triisopropylsilyl)digermene
(4).[9] Reaction of dichlorodimesitylsilane with 3b allowed us
to prepare unsymmetrically substituted 2,2-bis(di-tert-butyl-
(methyl)silyl)-1,1-dimesitylgermasilene (5) as a red-brown
solid in 77% yield (Scheme 2).[10, 11]
[4] The intermediate formation of Ph2GeLi2 was suggested by Mochida:
a) K. Mochida, N. Matsushige, M. Hamashima, Bull. Chem. Soc. Jpn.
¬
1985, 58, 1443 and later also reported by Satge: b) A. Castel, P.
¬
Riviere, J. Satge, H. Y. Ko, J. Organomet. Chem. 1988, 342, C1; c) A.
¬
Castel, P. Riviere, J. Satge, H. Y. Ko, Organometallics 1990, 9, 205.
There were also reports on the formation of intermediate Mes(H)-
iPr3Si
iPr3Si
SiiPr3
SiiPr3
¬
GeLi2: d) A. Castel, P. Riviere, J. Satge, D. Desor, J. Organomet.
THF
RT
+
+
(iPr3Si)2GeCl2
3a
Ge Ge
Chem. 1992, 433, 49 and Et2GeLi2: e) D. A. Bravo-Zhivotovskii, S. D.
Pigarev, O. A. Vyazankina, N. S. Vyazankin, Zh. Obshch. Khim. 1987,
57, 2644; J. Gen. Chem. 1987, 57, 2356. The formation of all
dilithiogermanes mentioned above was confirmed by trapping reac-
tions without isolation.
4
tBu2MeSi
tBu2MeSi
Mes
Mes
[5] A. Sekiguchi, M. Ichinohe, S. Yamaguchi, J. Am. Chem. Soc. 1999, 121,
10231.
THF
RT
Mes2SiCl2
3b
Ge
Si
[6] a) M. P. Egorov, S. P. Kolesnikov, Y. T. Struckov, M. Y. Antipin, S. V.
Sereda, O. M. Nefedov, J. Organomet. Chem. 1985, 290, C27; b) W.
Ando, H. Ohgaki, Y. Kabe, Angew. Chem. 1994, 106, 659; Angew.
Chem. Int. Ed. Engl. 1994, 33, 659; c) N. Tokitoh, K. Kishikawa, T.
Matsumoto, R. Okazaki, Chem. Lett. 1995, 827; d) N. Fukaya, M.
Ichinohe, Y. Kabe, A. Sekiguchi, Organometallics 2001, 20, 3364.
[7] Crystal structure analysis of 3b: Single crystals for X-ray analysis were
obtained by recrystallization from benzene. Diffraction data were
collected at 150 K on a MacScience DIP2030 K Image Plate Diffrac-
tometer with graphite-monochromated MoKa radiation (l ˆ
0.71070 ä). Crystal data: [{tBu2MeSi)2GeLi2(THF)2}2] ¥ C6H6,
C58H122Ge2Li4O4Si4, Mr ˆ 1168.86, monoclinic, space group ˆ P21/c,
a ˆ 11.2220(8), b ˆ 18.699(1), c ˆ 16.886(1) ä, b ˆ 102.550(4), Vˆ
5
Scheme 2. Synthesis of double bonded derivatives of Group 14 elements;
Mes ˆ 2,4,6-trimethylphenyl.
Experimental Section
Compound 2b: Dichlorobis(di-tert-butyl(methyl)silyl)germane (3.7g,
8.1 mmol) was heated under reflux with an excess of potassium (2.2 g,
57mmol) in bis(trimethylsilyl)acetylene (120 mL) for 19 h. After removal
of the inorganic salts by filtration and removal of the solvent in vacuo, the
residue was recrystallized from pentane to give 2b as colorless crystals
(3.7g, 81%). M.p. 125 127 8C (dec.); 1H NMR (300 MHz, [D6]benzene,
TMS): d ˆ À0.02 (s, 6H), 0.38 (s, 18H), 1.15 (s, 36H); 13C{1H} NMR
3458.7(4) ä3, Z ˆ 2, 1calcd ˆ 1.122 gcmÀ3
,
GOF ˆ 1.024. The final
R factor was 0.0607( Rw ˆ 0.1743 for all data) for 8186 reflections
with Io > 2s(Io). Crystal data for 2b at 120 K: C26H60GeSi4, Mrˆ
557.69, monoclinic, space groupˆ P21/c, a ˆ 19.3030(6), b ˆ
11.0260(5), c ˆ 18.1070(7) ä, b ˆ 118.032(2)8, Vˆ 3401.1(2) ä3, Z ˆ
ˆ
(75.5 MHz, [D6]benzene, TMS): d ˆ À4.9, 1.2, 22.1, 30.1, 165.3 (C C);
4, 1calcd ˆ 1.089 gcmÀ3
GOF ˆ 1.040, R ˆ 0.0632, Rw ˆ 0.0861. The
,
29Si{1H} NMR (59.6 MHz, [D6]benzene, TMS): d ˆ À9.6, 23.9; HRMS m/z:
structure was solved by the direct method and refined by the full-
matrix least-squares method using the SHELXL-97program. CCDC-
173500 for 2a, CCDC-173501 for 2b, and CCDC-173502 for 3b
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data Centre,
12, Union Road, Cambridge CB2 1EZ, UK; fax: (‡44)1223-336-033;
or deposit@ccdc.cam.ac.uk).
calcd. for C26H60GeSi4: 558.2989, found: 558.2992.
Compound 3b: The germacyclopropene 2b (55 mg, 0.1 mmol) was treated
with an excess of lithium (15 mg, 2.2 mmol) in a dry, oxygen-free mixture of
Et2O (1.6 mL) and THF (0.4 mL) at room temperature for 2.5 h, to give a
red-brown reaction mixture. After the reaction was complete, the solvents
and bis(trimethylsilyl)acetylene were removed in vacuo. Then dry toluene
(1.5 mL) was added to the solid residue and excess lithium was removed by
filtration in a glovebox. After evaporation of toluene, the residue was
washed with pentane to give a pale yellow powder 3b (39 mg, 71%).
1H NMR (300 MHz, [D8]THF, TMS): d ˆ 0.12 (s, 6H), 1.03 (s, 36H);
[8] K. M. Baines, W. G. Stibbs, Coord. Chem. Rev. 1995, 145, 157.
[9] M. Kira, T. Iwamoto, T. Maruyama, C. Kabuto, H. Sakurai, Organo-
metallics 1996, 15, 3767.
Angew. Chem. Int. Ed. 2002, 41, No. 9
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[10] Spectral data for 5: red-brown solid; m.p. 92 938C; 1H NMR
(300 MHz, [D6]benzene, TMS): d ˆ 0.15 (s, 6H), 1.17(s, 36H), 2.06
(s, 12H), 2.81 (s, 6H), 6.73 (s, 4H); 13C{1H} NMR (75.5 MHz,
[D6]benzene, TMS): d ˆ À3.2, 22.5, 25.8, 30.3, 30.6, 128.8, 139.1, 139.2,
143.6; 29Si{1H} NMR (59.6 MHz, [D6]benzene, TMS): d ˆ 31.4, 146.9
selectivity. In connection with our studies on bioactive and
highly ordered peptides, we undertook the synthesis of both
stereoisomers of 4-trifluoromethyl-l-proline. These building
blocks are expected to have profound conformational effects
on their host structures, which arise from the electronegative
nature of the trifluoromethyl group.
Our strategy for the preparation of the title compounds
employs asymmetric hydrogenation of the pyrrolines shown
in Scheme 1. For the synthesis of the cis isomer, the facial
ˆ
(Si Ge); HRMS m/z: calcd for C36H64GeSi3: 654.3536, found:
654.3531; UV/Vis (hexane) lmax(e): 237 (31700), 289 (8700), 430 nm
(5300).
[11] We recently reported stable germasilenes: a) 2-disilagermirene: V. Ya.
Lee, M. Ichinohe, A. Sekiguchi, N. Takagi, S. Nagase, J. Am. Chem.
Soc. 2000, 122, 9034; b) 1,2-disila-3-germacyclopenta-2,4-diene: V. Ya.
Lee, M. Ichinohe, A. Sekiguchi, J. Am. Chem. Soc. 2000, 122, 12604;
ˆ
c) (tBu2MeSi)2Si GeMes2: M. Ichinohe, Y. Arai, A. Sekiguchi, N.
Takagi, S, Nagase, Organometallics 2001, 20, 4141.
R1
OPG2
N
PG1
cis isomer
A
B
R1
OR2
N
PG1
R1
R2 = H or PG2
OH
Stereoselective Synthesis of Boc-Protected cis
and trans-4-Trifluoromethylprolines by
Asymmetric Hydrogenation Reactions**
N
PG1
trans isomer
Scheme 1. Strategies for the asymmetric hydrogenation of pyrroline
intermediates. A ˆ Sterically directed hydrogenation, B ˆ hydroxy-direct-
ed hydrogenation.
Juan R. Del Valle and Murray Goodman*
The effect of the proline residue on peptide conforma-
3]
tion[1 has been the impetus for the design of various
selectivity of the hydrogenation was expected to depend on
steric factors, which result from protection of the hydroxy
functionality as an ether or ester moiety. We were unable to
find previous syntheses of trans-substituted prolines that
exploit the potential for hydroxy-directed hydrogenation of
pyrroline intermediates. We envisioned this as a viable route
towards the trans-proline isomer as well as related analogues.
The retrosynthesis in Scheme 2 shows Boc-4-prolinone
(Boc ˆ tert-butoxycarbonyl) as a precursor to the desired
pyrrolines.
unnatural substituted prolines. These amino acid surrogates
have featured in a number of biologically active[4 7] and highly
ordered peptides.[8, 9] Prolines substituted at the 4-position
have been shown to enhance the thermal stability of collagen-
mimetic triple helices, with trans-4-fluoroproline yielding the
12]
most striking results.[10 The nature of the functional group
and the steric constraints imposed by the C4 substituent can
greatly influence the conformation of the pyrrolidine ring, as
well as the rate of cis trans isomerization about the amide
bond.[13 15] For these reasons, the preparation of 4-substituted
prolines is an attractive goal in peptidomimetic chemistry.
The synthesis of cis-4-phenylproline by a hydrogenolysis
reaction, which starts from hydroxyproline was recently
described by Hruby and co-workers.[16] In addition, Nevalai-
nen et al. reported a preparation of Fmoc-trans-4-methylpro-
line (Fmoc ˆ 9-fluorenylmethoxycarbonyl) by asymmetric
hydrogenation, which yields the desired isomer in a 6:1
diastereomeric ratio before purification.[17] Although these
and other syntheses of 4-substituted prolines are in the
literature,[18 21] a number of desirable targets continue to pose
a synthetic challenge. In particular, several trans-substituted
prolines have been difficult to synthesize with high stereo-
O
F3C
CH2OR1
CO2CH3
Hyp-OMe
N
N
Boc
Boc
R
1 = H, or PG2
Scheme 2. Retrosynthesis of Boc-4-trifluormethyl-l-proline; Hyp ˆ hy-
droxyproline.
The
synthesis
of
Boc-4-trifluoromethyl-l-proline
(Scheme 3) begins with the methyl ester of commercially
available and inexpensive trans-4-hydroxyproline (1). Boc-
protection was carried out under normal conditions, followed
by oxidation using trichloroisocyanuric acid and catalytic
2,2,6,6-tetramethyl-1-piperidinoxyl (free radical; TEMPO)[22]
to give ketone 3.
With the protected prolinone in hand, the trifluoromethyl
group was introduced by treatment of 3 with trimethyl(tri-
fluoromethyl)silane, in the presence of a fluoride initiator[23, 24]
to afford the tertiary alcohol 4 in 56% yield. Compound 4 was
[*] Prof. Dr. M. Goodman, J. R. Del Valle
Department of Chemistry and Biochemistry
University of California, San Diego
La Jolla, CA 92093 (USA)
Fax : (‡1)858-534-0202
E-mail: mgoodman@ucsd.edu
[**] The authors wish to thank Dr. Peter Gantzel for X-ray diffraction
studies. This work was supported by a grant from the NSF (DMR-
0111617). J.R.D. gratefully acknowledges the support of a San Diego
Fellowship; Boc ˆ tert-butoxycarbonyl.
a
single diastereomer which we presumed to be the
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
2S,4S isomer from the steric implications of the reaction.
1600
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4109-1600 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 9