A novel synthesis of (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2- dioxaborinanes and their conversion into carboxylic acids

Article abstract of DOI:10.1016/j.tetlet.2005.05.135

A novel procedure for preparing heterocyclic compounds such as (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes based on 1-trimethylgermyl-1-alkynes is described. 1-Trimethylgermyl-1-alkynes easily obtainable by deprotonation of 1-alkynes with n-butyllithium followed by treatment with trimethylgermanium chloride, are readily hydroborated in n-pentane in the presence of boron trichloride in hexane at 0°C for 3 h. The resulting supernatant clear solution was separated from boron trichloride-methyl sulfide complex. It was then reacted with 1,3-propane diol at 0°C for 0.5 h. The resulting representative (Z)-2-(1-trimethylgermyl-1- alkenyl)-1,3,2-dioxaborinanes were isolated in good yields (65-86%) and in high stereochemical purities (>98%) as evidenced by NMR spectral data. The carbon skeletons present in these intermediates were confirmed by alkaline hydrogen peroxide oxidation to the corresponding carboxylic acids.

Full text of DOI:10.1016/j.tetlet.2005.05.135

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5109–5111
A novel synthesis of (Z)-2-(1-trimethylgermyl-1-alkenyl)-
1,3,2-dioxaborinanes and their conversion into carboxylic acids
Narayan G. Bhat,* Zerremi Caga-Anan and Reynaldo Leija
Department of Chemistry, University of Texas–Pan American, 1201 West University Drive, Edinburg, TX 78541-2999, USA
Received 23 May 2005; accepted 31 May 2005
Available online 15 June 2005
Abstract—A novel procedure for preparing heterocyclic compounds such as (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborin-
anes based on 1-trimethylgermyl-1-alkynes is described. 1-Trimethylgermyl-1-alkynes easily obtainable by deprotonation of 1-alky-
nes with n-butyllithium followed by treatment with trimethylgermanium chloride, are readily hydroborated in n-pentane in the
presence of boron trichloride in hexane at 0 ꢀC for 3 h. The resulting supernatant clear solution was separated from boron trichlo-
ride–methyl sulfide complex. It was then reacted with 1,3-propane diol at 0 ꢀC for 0.5 h. The resulting representative (Z)-2-(1-tri-
methylgermyl-1-alkenyl)-1,3,2-dioxaborinanes were isolated in good yields (65–86%) and in high stereochemical purities (>98%)
as evidenced by NMR spectral data. The carbon skeletons present in these intermediates were confirmed by alkaline hydrogen
peroxide oxidation to the corresponding carboxylic acids.
ꢁ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Presumably, the hydrogen bromide generated caused
the degermylated product.
The syntheses of stereodefined alkenyl gem-dimetallic1–6
compounds are well documented in the literature. We
wanted to undertake a stereospecific synthesis of an
alkenyl gem-dimetallic compound such as the prepara-
tion of (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxa-
borinane via the hydroboration of 1-trimethylgermyl-
1-alkyne with dibromoborane–methyl sulfide complex
followed by the reaction with 1,3-propane diol. To our
surprise, we obtained degermylated product (Eq. 1).
Consequently, we explored a different procedure to
prepare (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxa-
borinanes involving the hydroboration of 1-trimethyl-
germyl-1-alkynes with dichloroborane–methyl sulfide7,8
complex in the presence of stoichiometric amount of
boron trichloride in hexane followed by the reaction
with 1,3-propane diol9 (Eq. 2). We herein report the
results of our investigation.
GeMe3
R
H
H
B
R
H
.
SMe
Br2 HB
2
HO(CH2)3OH
CGeMe3
C
RC
C
C
C
CH2Cl2
.
ð1Þ
ð2Þ
B SMe2
O
O
Br
Br
GeMe3
HO(CH2 )3OH
R
R
GeMe3
O
.
BHCl2
SMe2
RC CGeMe3
C
C
C
C
BCl
3 /hexane
H
BCl2
H
.
B
BCl3 SMe2
O
Keyword: Carboxylic acid.
*
Corresponding author. Tel.: +1 956 381 3373; fax: +1 956 384 5006; e-mail: nbhat@panam.edu
0040-4039/$ - see front matter ꢁ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.135

5110
N. G. Bhat et al. / Tetrahedron Letters 46 (2005) 5109–5111
..
.
.
+
O
C
. .
Na
O
C
..
+
H2O
.
.
RCH2
GeMe3
HOO Na
..
RCH2
GeMe3
+
RCH2COOGeMe3
RCH2COOH
O
OH
Scheme 1.
2. Results and discussions
3. Conclusions
In a typical experiment,10 1-trimethylgermyl-1-hexyne
was prepared by the deprotonation of 1-hexyne with n-
butyllithium at ꢀ78 ꢀC followed by treatment with tri-
methylgermanium bromide. It was then hydroborated
with dichloroborane–methyl sulfide complex in the
presence of stoichiometric amount of boron trichloride
at 0 ꢀC for 3 h. The product was isolated in 78% yield
and characterized as (Z)-2-(1-trimethylgermyl-1-hex-
enyl)-1,3,2-dioxaborinane by NMR spectral data. Using
the above procedure representative (Z)-2-(1-trimethyl-
germyl-1-alkenyl)-1,3,2-dioxaborinanes (Eq. 2) were
prepared (see Table 1). The carbon skeletons present in
these intermediates were confirmed by oxidation with
alkaline hydrogen peroxide followed by acidification of
the corresponding carboxylic acids11 (Eq. 3, Table 1).
In summation, we have developed a novel method to
prepare the (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-
dioxaborinanes for the first time based on 1-trimethyl-
germyl-1-alkynes in good yields. The carbon skeletons
present in these heterocyclic compounds were confirmed
by converting them into the corresponding carboxylic
acids. We are currently exploring the synthetic versatil-
ity of these promising stereodefined alkenyl gem-dime-
tallic intermediates by converting them into a variety
of products.
Acknowledgements
We are grateful to the Robert A. Welch Foundation of
Texas, for financial support under Grant BG-1387.
GeMe3
O
NaOH
H2O2
R
H
C
C
RCH2COOH
H3O+
References and notes
ð3Þ
B
O
1. Clift, S. M.; Schwartz, J. J. Organomet. Chem. 1985, 285,
C5, and references cited therein.
2. Tucker, C. E.; Knochel, P. J. Am. Chem. Soc. 1991, 113,
1988.
3. Marek, I.; Lefrancois, J.; Normant, J. F. J. Org. Chem.
1994, 59, 4154.
4. Knochel, P. J. Am. Chem. Soc. 1990, 112, 7431.
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1992, 33, 5861.
6. Zheng, B.; Srebnik, M. Tetrahedron Lett. 1994, 35, 1145.
7. Brown, H. C.; Ravindran, N. J. Org. Chem. 1977, 42,
2533.
Most probably, the initial oxidation must have pro-
duced acylgermanes as intermediates. The conversion
of these to the substituted acetic acids can be envisioned
to involve nucleophilic addition of hydroperoxy anion
to acylgermane followed by a rearrangement of germa-
nium to oxygen and loss of hydroxide (Scheme 1). A
similar mechanism has been proposed in the case of
acylsilanes12–14 undergoing oxidation to the carboxylic
acids with alkaline hydrogen peroxide.
8. Hassner, A.; Soderquist, J. A. J. Organomet. Chem. 1977,
131, C1.
9. Brown, H. C.; Bhat, N. G.; Somajaji, V. Organometallics
1983, 2, 1311.
Table 1. The synthesis of (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-
dioxaborinanes and their conversion into carboxylic acids
GeMe3
NaOH
H2O2
10. The preparation of (Z)-2-(1-trimethylgermyl-1-hexenyl)-
1,3,2-dioxaborinane is representative: In an oven dried
100 mL side-arm round bottom flask equipped with a
septum inlet were placed 10 mL of n-pentane and 1-
trimethylgermyl-1-hexyne (10 mmol, 1.99 g) under nitro-
gen atmosphere. The solution was cooled to 0 ꢀC and the
dichloroborane–methyl sulfide complex (10 mmol, 1.45 g)
was added dropwise followed by a solution of boron
trichloride in hexane (10 mmol, 10 mL, 1 M solution in
hexane). The resulting mixture was stirred for 3 h at 0 ꢀC
followed by 1 h at room temperature. The supernatant
solution was transferred to another 100 mL round bottom
flask and the solution was cooled to 0 ꢀC. To this cooled
solution was added 1,3-propane diol (10 mmol, 0.76 g)
dropwise and the resulting reaction mixture was stirred at
0 ꢀC for 0.5 h. The hydrocarbon layer containing the
desired product was separated and the solvent was
removed to provide the (Z)-2-(1-trimethylgermyl-1-hexen-
yl)-1,3,2-dioxaborinane in 78% (2.20 g) yield. The 1H
R
H
C
C
RCH2COOH
O
H3O+
B
O
No.
R =
n-C4H9
Carboxylic acid
Yielda (%)
1
2
3
4
5
6
n-C4H9
n-C5H11
n-C6H13
–C(CH3)3
–(CH2)3Cl
–Ph
78
75
86
68
70
65
n-C5H11
n-C6H13
–C(CH3)3
–(CH2)3Cl
–Ph
a All of the reactions were carried out on a 10 mmol scale. The yields
are isolated yields of carboxylic acids based on the (Z)-2-(1-tri-
methylgermyl-1-alkenyl)-1,3,2-dioxaborinanes. The spectral data
(1H NMR and 13C NMR) were consistent with the proposed
carboxylic acids.

N. G. Bhat et al. / Tetrahedron Letters 46 (2005) 5109–5111
5111
NMR and 13C NMR spectral data indicated that the
compound isolated is a crude product, which was not
purified further. The 13C NMR spectrum revealed a peak
at d 157.42 ppm characteristic of an olefinic carbon atom.
The quaternary alkenyl carbon was not indicated in
13C NMR spectrum. Had it been a mixture of E- and
Z-isomers, we would have observed two peaks in the
olefinic region of the 13C NMR spectrum. Since the hydro-
boration is a syn-addition, we concluded that the double
bond present in the compound has Z-configuration.
attain room temperature and the stirring was continued
for 4 h at room temperature. An additional 5 mL of 3 M
sodium hydroxide was added. The reaction mixture was
washed twice with ether (2 · 30 mL). Acidification of the
aqueous phase was performed with concentrated hydro-
chloric acid. It was then extracted with ether (2 · 30 mL)
followed by the removal of ether provided n-hexanoic acid
in 78% (0.90 g) isolated yield. The compound was char-
1
acterized by IR, H NMR, and 13C NMR spectral data.
IR (neat): <2926 and 1718 cmꢀ1 1H NMR (CDCl3/
;
11. The preparation of n-hexanoic acid from the (Z)-
2-(1-trimethylgermyl-1-hexenyl)-1,3,2-dioxaborinane
without TMS): d 0.8 (3H, m), 1.28–1.57 (6H, m), 2.30 (2H,
m), and 11.75 (1H, s) ppm; 13C NMR (CDCl3/without
TMS): d 13.79, 22.31, 24.37, 31.24, 34.11, and 180.74 ppm.
12. Zweifel, G.; Backlund, S. J. J. Am. Chem. Soc. 1977, 99,
3184.
13. Eisch, J. J.; Husk, G. R. J. Org. Chem. 1964, 29,
254.
14. Brook, A. G. Acc. Chem. Res. 1974, 7, 77.
is
representative: To a solution of (Z)-2-(1-trimethylgermyl-
1-hexenyl)-1,3,2-dioxaborinane (10 mmol, 2.85 g) in tetra-
hydrofuran (10 mL) was added 5 mL of methanol. It was
then cooled to 0 ꢀC and sodium hydroxide (3 M, 5 mL)
was added followed by 30% hydrogen peroxide slowly
(25 mmol, 2.5 mL). The reaction mixture was allowed to