Synthesis and asymmetric hydrogermylation reactions of dithiogermanium hydrides derived from C2-symmetric dithiols

Article abstract of DOI:10.1055/s-2001-14655

Two members of a new class of dithiogermanium hydrides have been prepared in racemic and enantiopure form. Reaction of 2,2′-dithiobinap and 3,3′-bis-trimethylsilyl-2,2′-dithiobinap with ^tBuGeCl₃ followed by reduction provides the corresponding germanium hydrides. Hydrogermylation of methyl methacrylate occurs with low selectivity (<3/1) for the former substrate but high selectivity (>10/1) for the latter.

Full text of DOI:10.1055/s-2001-14655

1
038
LETTER
Synthesis and Asymmetric Hydrogermylation Reactions of Dithiogermanium
Hydrides Derived from C2-Symmetric Dithiols
Dennis P. Curran, Giovanna Gualtieri
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA15260, USA
Received 15 February 2001
Dedicated to Prof. Ryoji Noyori for his enduring contributions to stereoselective synthesis.
R3
Abstract: Two members of a new class of dithiogermanium hy-
drides have been prepared in racemic and enantiopure form. Reac-
R
Sn
H
X
R
Sn
H
tion of 2,2 -dithiobinap and 3,3 -bis-trimethylsilyl-2,2 -dithiobinap
t
with BuGeCl followed by reduction provides the corresponding
X
3
germanium hydrides. Hydrogermylation of methyl methacrylate
occurs with low selectivity (<3/1) for the former substrate but high
selectivity (>10/1) for the latter.
R3'
1
1
a
b
R = Me
R = Bu
2
3
4
X = CH2
X = O
X = S
t
Key words: hydrogermylation, germanium hydrides, stereoselec-
tivity
Figure 1
Despite the fast pace of advances in enantioselective rad-
1
ical reactions, asymmetric reactions of chiral tin
2
hydrides still present a significant challenge. In 1996, we the solid state. Unfortunately, we were not able to reduce
introduced the first enantiopure tin hydride 1a fashioned 6a to the corresponding tin hydride (rac)-7a, despite ex-
from the popular C2-symmetric binaphthyl motif (Figure tensive effort. A few reducing agents (for example AlH
3
3
1
). Radical reductions with this tin hydride gave products and Bu
with low to moderate ees (up to 40%). In independent most (for example, LiAlH
work, Metzger and coworkers reported the t-butyl analog to return the starting dithiol 5a. Presumably, the Sn S
3
SnH) returned unreacted starting material, but
and DIBAL) disassembled 6a
4
4
1
b, which gave somewhat better ees (up to 50%). This bonds were reduced along with the Sn Cl bond by these
5
6
level has since been passed by Schiesser and Hoshino by reductants.
using tin hydrides in conjunction with Lewis acids. How-
7
ever, it is still of interest to develop asymmetric reactions
that are controlled by the tin hydride alone. In this regard,
we envisioned that it might be interesting to build a tin hy-
dride inside a cleft that could better influence the geome-
try of an approaching radical. We report herein
preliminary results that led us to synthesize two dithioger-
mane hydrides 9a and 9b as alternatives for the traditional
tin hydride. Hydrogermylation of methyl methacrylate
with one of the germanium hydrides occurs with high se-
lectivity.
SH
S
S
Bu
Sn
Cl
BuSnCl3 or
i
SH BuSn(O Pr)2Cl
(
rac)-5a
(rac)-6a
S
S
Bu
reduce
Sn
8
9
Inspired by the work of Yamamoto, Wulff, and others,
we envisioned that addition of substituents at C3 and C3
on the binap ring would influence the approach of radicals
to the hydrogen atom of a tin hydride, and we evaluated a
number of approaches to make molecules like 2 (Figure
H
(rac)-7a
Equation 1
1
). Analogs 2 with the CH bridge are the direct descen-
2
dants of 1, but these might not be straightforward to make.
3
We spent some time trying to make analogs 3 (R ,
To strengthen the bond to sulfur, we then explored the nu-
clear substitution of tin by germanium. Germanium hy-
drides are well known if rarely used alternatives to tin
3
R = H) with an oxygen bridge, but the Sn O bonds in
these molecules seemed too labile. Recognizing that tin-
1
0
sulfur bonds are more robust, we next moved to the sul-
12
hydrides in radical reactions. Trialkylgermanium hy-
3
3
fur analogs 4 (R , R = H).
drides are poorer hydrogen donors than related tin hy-
1
1
Reaction of the racemic dithiobinap (rac)-5a with either drides; however, there is reason to expect that this rate
BuSnCl or BuSn(OiPr) Cl produced dithiotin chloride retarding effect could be offset by an activating effect of
3
2
rac)-6a (eq 1). As hoped, this proved to be quite stable in the two thio substituents.13 Thio-substituted germanium
(
Synlett 2001, SI, 1038–1041 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Asymmetric Hydrogermylation Reactions of Dithiogermanium Hydrides
1039
1
4
hydrides are a relatively rare class of molecules whose
members have not to our knowledge been previously used
for radical chain reactions. Only a few chiral germanium
Br
H
(rac)-9a
AIBN, 80 °C
benzene
1
5
hydrides are known, and chiral dithiogermanium hy-
88% GC yield
drides are unknown.
t
Reaction of racemic dithiol 5a with BuGeCl in THF pro-
CCl4
3
(rac)-9a
(rac)-8a
100% NMR yield
vided the crystalline germanium chloride (rac)-8a in over
AIBN, 80 °C
9
5% yield (eq 2; note, eq 2 shows single enantiomers
only). This was a relatively stable molecule as a solid and
in solution and it could be handled without any special
precautions. But it slowly hydrolyzed to the germanium
hydroxide in the presence of moisture. Reduction of the
germanium chloride (rac)-8a to the hydride (rac)-9a again
proved problematic, but could be accomplished under
carefully controlled conditions. Reduction in THF with
sodium borohydride followed by standard extractive
workup with a base wash gave germanium hydride (rac)-
Equation 3
groups.17,18 Conversion to the dithiogermanium chloride
b was straightforward, but reduction to 9b again required
8
great care to prevent over-reduction to return 5b. Howev-
er, both racemic and enantiopure hydrides 9b could be pu-
rified by recrystallization (>95% pure, 65-80% yield).
9
a contaminated with <2% of the dithiol (rac)-5a and trac-
In a preliminary assessment of the structural effects on
stereochemistry, we conducted hydrometallations of me-
thyl methacrylate with the previously reported (S)-trialk-
R3
R3
S
3
tBuGeCl3
tBu
Cl
SH
SH
yltin hydride 1a and both of the new dithiogermanium
Ge
hydrides 9a,b (both racemic and enantiopure) under stan-
dard conditions. The results of some representative exper-
iments are shown in Figure 2 and the Table.
Hydrostannation with (S)-1a provided 10a/11a in a ratio
of 1.3/1. The diastereomeric products were not separable,
and the relative configurations were not assigned. Hy-
drogermylation with (rac)-9a provided (rac)-12a/13a in a
1.7/1 ratio, while the use of (R)-9a gave enantiopure 12a/
3
Et N, THF
S
R3'
R3'
3
3'
(
(
R)-5a R , R = H
(R)-8a
(R)-8b
3
3'
R)-5b R , R = TMS
R3
S
NaBH4
or LiBH4
tBu
H
Ge
1
3a in a 3/1 ratio. These products were separated by
THF
S
chromatography, and the crystal structure of the minor
isomer was solved to assign the relative configuration.
R3'
(
(
R)-9a
R)-9b
In contrast to these relatively low selectivities, hydroger-
mylation with 9b was quite selective. Racemic 9b provid-
ed racemic 12b/13b in an 11/1 ratio at room temperature
and a 14/1 ratio at 20 °C, while the use of (R)-9b gave
enantiopure 12b/13b in improved ratios: 15/1 at 25 °C and
Note: Eq 2 shows single enantiomers. Racemates (rac)-5a/b,
rac)-7a/b and (rac)-8a/b were also made.
(
Equation 2
2
5/1 at 20 °C. The major isomer 12b could be isolated in
es of another unidentified impurity. This could be further
purified by chromatography at the expense of extensive
material loss (30-40%), and it was generally used in crude
form.
R3
R3
CH3
CO2Me
X
X
R
H
R
X
X
M
M
CH3
•
AIBN, hν
or Et3B
Two simple reactions demonstrated that (rac)-9a moder-
ates radical chain reductions. Reduction of adamantyl bro-
mide under standard condition provided adamantane in
CO2Me
R3'
R3'
1a, 9a, 9b
8
8% GC yield. To assess the germanium product, we re-
R3
R3
acted (rac)-9a in CCl (solvent), and showed in an NMR
experiment that germanium chloride (rac)-8a was formed
in quantitative yield. The enantiopure germanium hydride
from (R)-9a was also prepared from (R)-5a, and its hy-
drogermylation reactions with methyl methacrylate are
presented below.
4
M*H
X
X
R
R
X
X
M
+
M
1
6
CO2Me
2
CO Me
R3'
R3'
R3, R3'
X
CH2
S
M
R
1a
10a
12a
12b
Sn
Ge
Ge
Me
H, H
H, H
11a
13a
13b
t
To evaluate the effects of bulky substituents at C3 and
C3 , germanium hydride 9b was prepared from both race-
mic and (R)-dithiol 5b bearing two trimethylsilyl
9a
Bu
t
9b
S
Bu TMS, TMS
Figure 2
Synlett 2001, SI, 1038–1041 ISSN 0936-5214 © Thieme Stuttgart · New York

1
040
D. P. Curran, G. Gualtieri
LETTER
Table Hydrometallation of Methyl Methacrylate with Tin Hy-
dride 1a and Germanium Hydrides 9a,b.
(3) Nanni, D.; Curran, D. P. Tetrahedron: Asymmetry 1996, 7,
2417.
(
4) a) Blumenstein, M.; Schwarzkopf, K.; Metzger, J. O. Angew.
Chem., Int. Ed. Engl. 1997, 36, 235. b) Schwarzkopf, K.;
Blumenstein, M.; Hayen, A.; Metzger, J. O. Eur J. Org. Chem.
1998, 177.
(5) Dakternieks, D.; Dunn, K.; Perchyonok, V. T.; Schiesser, C.
H. Chem. Commun. 1999, 1665.
(
6) a) Murakata, M.; Tsutsui, H.; Hoshino, O. J. Chem. Soc.,
Chem. Commun. 1995, 481. b) Murakata, M.; Tsutsui, H.;
Takeuchi, N.; Hoshino, O. Tetrahedron 1999, 55, 10295.
7) Renaud, P.; Gerster, M. Angew. Chem., Int. Ed. Engl. 1998,
(
(
(
37, 2563.
8) Yamamoto, H.; Maruoka, K.; Ishihara, K. J. Syn. Org. Chem.
Jpn. 1994, 52, 912.
9) Bao, J. M.; Wulff, W. D.; Rheingold, A. L. J. Am. Chem. Soc.
1993, 115, 3814.
(
(
(
(
10) a) Chemistry of Tin; 2nd ed.; Smith, P. J., Ed.; Blackie:
London, 1997. b) Davies, A. G. Organotin Chemistry; VCH:
Weinheim, 1997.
a) Isolated yield of mixture unless otherwise indicated; b) by NMR
analysis; c) configurations of 10a/11a not known; d) by HPLC
analysis; e) isolated yield of pure 12b.
11) a) Fabbri, D.; Delogu, G.; De Lucchi, O. J. Org. Chem. 1993,
58, 1748. b) Bandarage, U. K.; Simpson, J.; Smith, R. A. J.;
Weavers, R.T. Tetrahedron 1994, 50, 3463.
12) Chatgilialoglu, C.; Newcomb, M. In Advances In
Organometallic Chemistry; R. West and A. F. Hill, Ed.;
Academic Press: San Diego, 1999; Vol. 44; pp 67.
13) Chatgilialoglu, C.; Guerra, M.; Guerrini, A.; Seconi, G.;
Clark, K. B.; Griller, D.; Kanabus-Kaminska, J.; Martinho-
Simões, J. A. J. Org. Chem. 1992, 57, 2427.
pure form by chromatographic purification, and the crys-
tal structure of the alcohol (not shown) obtained by
DIBAL reduction was solved to assign the relative con-
figuration.
The change from dialkyltin hydride 1a to dithiogermani- (14) a) Drake, J. E.; Glavincevski, B. M.; Henderson, H. E. Inorg.
Nucl. Chem. Lett. 1977, 13, 565. b) Drake, J. E.; Hemmings,
R. T.; Henderson, E. J. Chem. Soc. Dalton Trans. 1976, 366.
c) Klein, B.; Neumann, W. P.; Weisbeck, M. P.; Wienken, S.
J. Organomet. Chem. 1993, 446, 149. d) Rivière, P.; Dousse,
G.; Satgé, J. Syn. React. Inorg. Metal-Org. Chem. 1974, 4,
281.
um hydride 9a has relatively little effect on the stereose-
lectivity, but the addition of the two trimethylsilyl groups,
9
b, has a strong beneficial effect. This supports the notion
that bulky substituents in the vicinity of the Ge H bond
can enhance selectivity. Two germaniums are involved in
the asymmetric hydrogen transfer step in a kind of double (15) a) Brook, A.G.; Peddle, G. J. D. J. Am. Chem. Soc. 1963, 85,
1
869. b) Brook, A.G.; Peddle, G. J. D. J. Am. Chem. Soc.
asymmetric induction. Comparison of the results with ra-
cemic and enantiopure hydrides suggests that the germa-
nium atom bonded to the radical plays the major role
while the germanium atom that donates the hydrogen en-
hances the selectivity somewhat if both germaniums are
of the same configuration (matched pair).
1963, 85, 2338. c) Bott, R. W.; Eaborn, C.; Varma, I. D. Chem.
Ind. 1963, 614. d) Eaborn, C.; Simpson, P.; Varma, I. D. J.
Chem. Soc. (A) 1966, 1133. e) Tacke, R.; Kosub, U.; Wagner,
S. A., Bertermann, R.; Schwarz, S.; Merget, S.; Günther, K.
Organometallics, 1998, 17, 1687. f) Colesdan, F.; Castel, A.;
Rivière, P.; Satgé, J. Veith, M.; Huch, V. ibid. 1998, 17, 2222.
16) De Lucchi, O.; Fabbri, D.; Delogu, G. J. Org. Chem. 1995, 60,
(
(
These results encourage further work on the design and
synthesis of tin, germanium or silicon hydrides where the
M H bond begins to reside in a cleft defined by the sub-
6599.
17) Cossu, S.; De Lucchi, O.; Fabbri, D.; Valle, G.; Painter, G. F.;
Smith R. A. J. Tetrahedron 1997, 53, 6073.
stituents. Detailed studies on the structure (x-ray, NMR) (18) Representative Procedures: 4-tert-Butyl-4-chloro-2,6-bis-
and reactivity (rate constants, ees) of the two new germa-
nium hydrides will be reported in a forthcoming full pa-
per.
trimethylsilyl-3,5-dithia-4-germa-cyclohepta[2,1-a;3,4-
a ]dinaphthalene (8b). Triethylamine (1 mL, 7.2 mmol) was
added dropwise to a stirred solution of 3,3 -bis(trimethylsilyl)-
1,1 -binaphto-2,2 -dithiol (5b) (845 mg, 1.8 mmol) and
t-BuGeCl (480 mg, 2.0 mmol)in THF (40 mL) at 0 °C. After
3
addition was complete, the ice bath was removed and the
reaction mixture allowed to warm to room temperature. After
stirring for 2 h, the mixture was diluted with diethyl ether and
filtered. The filtrate was concentrated under reduced pressure
and the residue recrystallized from hexanes to afford 1.11 g
Acknowledgement
We thank the National Science Foundation for funding this work.
We also thank Dr. Steven Geib for solving the crystal structures.
(
4
97%) of 8b as white crystals.
-tert-Butyl-2,6-bis-trimethylsilyl-3,5-dithia-4-germa-
References and Notes
cyclohepta[2,1-a;3,4-a ]dinaphthalene (9b). Lithium
borohydride (2.0 M solution in THF, 6.2 mL, 12.4 mmol) was
added to a stirred solution of 8b (388 mg, 0.62 mmol) in THF
(
(
1) Sibi, M. P.; Porter, N. A. Acc. Chem. Res. 1999, 32, 163.
2) a) Gielen, M. Top. Curr. Chem. 1982, 104, 57. b) Schumann,
H.; Wasserman, B. C.; Pickardt, J. Organometallics 1993, 12,
(
20 mL) at 0 °C. The reaction mixture was kept at –8 °C
3051. c) Podestá, J. C.; Chopa, A. B.; Radivoy, G. E.; Vitale,
without stirring for 5 days, then it was diluted with diethyl
C. A. J. Organomet. Chem. 1995, 494, 11.
ether and poured into 100 mL of cold NH Cl aqueous solution
4
Synlett 2001, SI, 1038–1041 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Asymmetric Hydrogermylation Reactions of Dithiogermanium Hydrides
1041
with stirring. The organic layer was separated and the aqueous
layer extracted with diethyl ether (2 x 30 mL). The combined
until TLC analysis showed complete conversion of the
germanium hydride. Triethylborane (1.0 M soln in hexanes,
25 L, 0.025 mmol) was added periodically if needed. After
completion, the crude mixture was filtered through a silica gel
plug and analyzed by HPLC. After removal of the solvent, the
crude mixture was subjected to column chromatography
(ethyl acetate/hexanes 2:98) or preparative HPLC (ethyl
acetate/hexanes 1:99) to give 55-77% yield of the adducts 12b
and 13b.
organic extracts were dried over MgSO , filtered and
4
concentrated under reduced pressure. After recrystallization
from hexanes, 285 mg of 9b (78%) were obtained as white
crystals.
General procedure for hydrogermylation of methyl
methacrylate with 9b. In a sealed tube purged with argon were
placed methyl methacrylate (2.0 equiv, 21 µL, 0.20 mmol),
the germanium hydride 9b (60 mg, 0.10 mmol) and toluene
(benzene for reactions at r.t., 1 mL). Triethylborane (1.0 M
soln in hexanes, 25 µL, 0.025 mmol) was then added and the
resulting mixture was stirred at the appropriate temperature
Article Identifier:
1437-2096,E;2001,0,SI,1038,1041,ftx,en;Y05701ST.pdf
Synlett 2001, SI, 1038–1041 ISSN 0936-5214 © Thieme Stuttgart · New York