Novel diastereoselective synthesis of (E)-gem-dimetalloalkenes containing boron and germanium: An easy access to alkyl trimethylgermyl ketones and carboxylic acids

Article abstract of DOI:10.1055/s-2007-984542

A convenient, novel synthesis of (E)-gem-dimetalloalkenes containing boron and germanium from the (Z)-1-bromo-1-alkenylboronate esters has been developed. α-Bromo-(Z)-1-alkenylboronate esters readily prepared from the literature procedures smoothly underwent a reaction with freshly generated trimethylgermyllithium in hexamethylphosphoramide (HMPA) from the hexamethyldigermanium at -78°C to provide the corresponding 'ate' complexes. These 'ate' complexes underwent intramolecular nucleophilic substitution reaction to provide the corresponding (E)-1-alkenylboronate esters containing trimethylgermyl moiety. These intermediates were isolated in good yields (72-81%) and were characterized by the spectral data (¹H NMR and ¹³C NMR). Upon oxidation of these intermediates with trimethylamine-N-oxide, the corresponding alkyl trimethylgermyl ketones were prepared in good yields (78-86%)). Oxidation with alkaline hydrogen peroxide followed by acidification afforded the corresponding carboxylic acids in good yields (82-88%). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984542

LETTER
2023
Novel Diastereoselective Synthesis of (E)-gem-Dimetalloalkenes Containing
Boron and Germanium: An Easy Access to Alkyl Trimethylgermyl Ketones
and Carboxylic Acids
S
N
ynthesis of
(
E
)-ge
a
m
-Dimeta
l
r
loalkene
a
s
C
ontainin
y
g Boron and
a
G
ermaniu mn G. Bhat,* Nisha Varghese
Department of Chemistry, University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA
Fax +1(956)3845006; E-mail: nbhat@panam.edu
Received 22 March 2007
2
1
,3-propane diol has been reported. It should be noted
Abstract: A convenient, novel synthesis of (E)-gem-dimetalloalk-
enes containing boron and germanium from the (Z)-1-bromo-1-alk-
enylboronate esters has been developed. a-Bromo-(Z)-1-
that these a-halo-(Z)-1-alkyenylboronate esters are
known to undergo intramolecular nucleophilic substitu-
alkenylboronate esters readily prepared from the literature proce- tion reactions3 with nucleophiles such as hydrides,
–6
7
8
8
dures smoothly underwent a reaction with freshly generated tri- Grignard reagents, organolithium reagents , allylmagne-
9
10
methylgermyllithium in hexamethylphosphoramide (HMPA) from sium bromide, trimethylsilylmethyllithium, and tri-
the hexamethyldigermanium at –78 °C to provide the corresponding
ate’ complexes. These ‘ate’ complexes underwent intramolecular
nucleophilic substitution reaction to provide the corresponding
E)-1-alkenylboronate esters containing trimethylgermyl moiety. esters with a nucleophilic reagent such as freshly prepared
These intermediates were isolated in good yields (72–81%) and trimethylgermyllithium in hexamethylphosphoramide
11
methylsilyllithium.
In this report, we reacted 1-bromo-(Z)-1-hexenylboronate
‘
(
1
13
were characterized by the spectral data ( H NMR and C NMR).
Upon oxidation of these intermediates with trimethylamine-N-
oxide, the corresponding alkyl trimethylgermyl ketones were pre-
pared in good yields (78–86%). Oxidation with alkaline hydrogen
peroxide followed by acidification afforded the corresponding
carboxylic acids in good yields (82–88%).
followed by oxidation with hydrogen peroxide and
sodium acetate (Scheme 1). Consequently, we describe a
facile general synthesis of (E)-gem-dimetalloalkenes con-
taining boron and germanium and their oxidation to alkyl
trimethylgermyl ketones and carboxylic acids based on
versatile intermediates such as a-bromo-(Z)-1-alkenyl-
boronate esters.
Key words: gem-dimetalloalkanes, trimethylgermyllithium, hexa-
methylphosphoramide
The required starting materials such as 1-bromo-1-
alkynes and a-bromo-(Z)-1-alkenylboronate esters were
1
2
The acylgermanes are important intermediates in organic prepared using literature procedures. In a typical experi-
synthesis. They are potential prochiral ketones for asym- ment, a-bromo-(Z)-1-hexenylboronate ester was reacted
metric reduction reactions. In view of the synthetic impor- with trimethylgermylllithium in hexamethylphosphor-
tance of alkyl trimethylgermyl ketones, it was desirable to amide (easily generated by reacting hexamethyldigerma-
have a general and convenient methodology for their nium with methyllithium1 at 0 °C for 0.5 h) at –78 °C
synthesis, especially from readily available organoborane under an inert atmosphere and the reaction mixture was
2a
reagents.
stirred at –78 °C for two hours followed by stirring over-
night at room temperature. The resulting product (entry 1
in Table 1, 81% yield) was isolated and purified by col-
umn chromatography over silica gel. It was then subjected
In a previous study, a stereoselective preparation of the
(
Z)-1-bromo-1-alkenylboronate esters via the hydrobora-
tion of 1-bromo-1-alkynes followed by treatment with
O
R
H
Br
B
R
H
B
Me3GeLi
HMPA
Me3NO
C
C
O
O
RCH2COGeMe3
78–86%
C
C
O
H2O
GeMe3
72–81%
NaOH
H2O2
HCl
3
RCH2COOH
2–88%
8
Scheme 1
SYNLETT 2007, No. 13, pp 2023–2024
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3
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8
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Advanced online publication: 27.06.2007
DOI: 10.1055/s-2007-984542; Art ID: S01507ST
Georg Thieme Verlag Stuttgart · New York
©

2
024
N. G. Bhat, N. Varghese
LETTER
to oxidation using trimethylamine-N-oxide (TMANO)12b borane intermediates containing trimethylgermyl moiety
in tetrahydrofuran at room temperature for 12 hours. After are currently underway.
workup, the reaction provided n-pentyl trimethylgermyl
ketone in 80% isolated yield. Using the above procedure,
the representative alkyl trimethylgermyl ketones were
Acknowledgment
prepared. Oxidation of the resulting (E)-1-trimethyl- We are grateful to the Robert A. Welch Foundation of Texas
under the grant number BG-1387 and the National Institute of
germyl-1-alkenylboronate esters (Table 1) with alkaline
Health-MBRS program under the grant number NIH-NIGMS
peroxide followed by acidic workup provided the corre-
sponding carboxylic acids (Scheme 1).
2
S06GM08038-32 for their generous financial support to undertake
this project.
Presumably, the starting a-bromo-(Z)-1-alkenylboronate
ester could form an ‘ate’ complex as a result of a reaction
with trimethylgermyllithium. This would further undergo
an anionotropic rearrangement involving the migration of
the trimethylgermyl group from boron to the adjacent
alkenyl carbon with inversion of configuration to provide
E-trisubstituted boron intermediate containing trimethyl-
germyl moiety, the oxidation of which would provide
alkyl trimethylgermyl ketones and carboxylic acids under
different oxidation conditions (Scheme 1).
References and Notes
(1) Curran, D. P.; Diederichsen, U.; Palovich, M. J. Am. Chem.
Soc. 1997, 119, 4797; and references cited therein.
(
(
(
(
2) Brown, H. C.; Bhat, N. G.; Somayaji, V. Organometallics
983, 2, 1311.
3) Matteson, D. S.; Majumdar, D. Organometallics 1983, 2,
529; and references cited therein.
4) Tsai, D. J. S.; Jesthi, P. K.; Matteson, D. S. Organometallics
1983, 2, 1543.
5) Brown, H. C.; De Lue, N. R.; Yamamoto, Y.; Maruyama, K.;
Kasahara, T.; Murahashi, S.; Sonoda, A. J. Org. Chem.
1977, 42, 4088.
1
1
Table 1 Stereoselective Synthesis of (E)-gem-Dimetalloalkenes
Containing Boron and Germanium
(
6) Rathke, M. W.; Chao, E.; Wu, G. J. Organomet. Chem.
Entrya
R
Isolated
yield
Germyl
ketones
Carboxylic
acids
1976, 122, 145.
b,c
(
(
7) Brown, H. C.; Imai, T. Organometallics 1984, 3, 1293.
8) Brown, H. C.; Imai, T.; Bhat, N. G. J. Org. Chem. 1986, 51,
1
2
3
4
5
6
n-Bu
81%
80%
78%
78%
72%
74%
80%
80%
86%
84%
78%
82%
78%
82%
82%
88%
85%
84%
82%
80%
82%
5
277.
9) Brown, H. C.; Soundararajan, R. Tetrahedron Lett. 1994, 35,
963.
(
n-C H
5
11
13
6
n-C H
(10) Bhat, N. G.; Martinez, C.; De Los Santos, J. Tetrahedron
Lett. 2000, 41, 6541.
(11) Bhat, N. G.; Tamm, A.; Gorena, A. Synlett 2004, 297.
12) (a) Still, W. C. J. Org. Chem. 1976, 41, 3063.
b) Soderquist, J. A.; Hassner, A. J. Am. Chem. Soc. 1980,
02, 1577.
13) In a mixture of isomers, the vinylic carbons of the Z alkenes
can be distinguished from the corresponding carbons of E-
alkenes: Dorman, D. E.; Jautelat, M.; Roberts, J. D. J. Org.
Chem. 1971, 36, 2757.
14) The preparation of n-hexanoic acid from the (E)-2-(1-tri-
methylgermyl-1-hexenyl)-1,3,2-dioxaborinane is represen-
tative: To a solution of (E)-2-(1-trimethylgermyl-1-
hexenyl)-1,3,2-dioxaborinane (10 mmol, 2.85 g) in THF (10
mL) was added MeOH (5 mL). It was then cooled to 0 °C
and NaOH (3 M, 5 mL) was added followed by the slow
addition of 30% H O (25 mmol, 2.5 mL). The reaction
6
Cl(CH2)3
t-Bu
(
(
1
CH CH CHMe
2
2
2
(
7
CH CH Ph
2 2
a
All compounds were oxidized with trimethylamine-N-oxide
(TMANO) to the corresponding alkyl trimethylgermyl ketones in
(
>
78% isolated yields. Oxidation with alkaline hydrogen peroxide fol-
lowed by acidification provided the corresponding carboxylic acids in
high yields (82–88%). They were characterized by spectral data (IR,
1
b
13
H NMR, and C NMR).
All reactions were carried out on a 5-mmol scale. The yields are
based on the corresponding a-bromo-(Z)-1-alkenylboronate esters.
2
2
c
All compounds were isolated by column chromatography over silica
mixture was allowed to come to r.t. and the stirring was
continued for 4 h at r.t. Also, 3 M NaOH (5 mL) was added.
gel and were characterized by IR and NMR spectral data. The
1
3
stereochemical purities of these intermediates were confirmed by
The reaction mixture was washed with Et O (2 × 30 mL).
1
13
2
H NMR and C NMR.
Acidification of the aqueous phase was performed with
concd HCl acid. It was then extracted with Et O (2 × 30 mL),
2
which was then removed via evaporation to provide n-
In summation, we have developed a novel synthetic route
for the preparation of alkyl trimethylgermyl ketones and
carboxylic acids based on the reactions of trimethyl-
germyllithium with a-bromo-(Z)-1-alkenylboronate
esters followed by oxidation studies. The representative
synthetic applications of these E-trisubstituted organo-
1
hexanoic acid in 82% (0.95 g) isolated yield. IR, H NMR,
13
and C NMR spectral data were used characterize the
1
4
–1 1
compound. IR (neat): <2926, 1718 cm . H NMR (CDCl /
3
without TMS): d = 0.8 (m, 3 H), 1.28–1.57 (m, 6 H), 2.30 (m,
2 H), 11.75 (s, 1 H). CMR (CDCl /without TMS): d = 13.79,
3
22.31, 24.37, 31.24, 34.11, 180.74.
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