Regioselectivity of selenium-mediated carbonylation of organolithium compounds with carbon monoxide

Article abstract of DOI:10.1080/10426501003773456

Regioselectivity of selenium-mediated carbonylation of organolithium compounds with carbon monoxide has been investigated. The reactions of lithium enolates of 2,2-dicyclohexyl aldehyde and 1,1-dicyclohexylpropane-2-one with selenium and carbon monoxide afforded the corresponding selenocarbonates by carbonylation at the enolate oxygen as the main product. Carbonylation of nitrogen-containing heterocycles can give either C- or N-carbonylation product, but diphenyl(4-pyridyno)methane, imidazole, and pyrazole afford only corresponding carbamoselenoates via N-carbonylation. Copyright Taylor & Francis Group.

Full text of DOI:10.1080/10426501003773456

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Phosphorus, Sulfur, and Silicon and the
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Regioselectivity of Selenium-Mediated
Carbonylation of Organolithium
Compounds with Carbon Monoxide
Shin-ichi Fujiwara a , Akira Nishiyama b , Kazuhiro Okada b , Hajime
Maeda b , Tsutomu Shin-ike a , Noboru Sonoda b & Nobuaki Kambe b
a Department of Chemistry , Osaka Dental University , Osaka, Japan
b Department of Applied Chemistry, Graduate School of
Engineering , Osaka University , Osaka, Japan
Published online: 27 May 2010.
To cite this article: Shin-ichi Fujiwara , Akira Nishiyama , Kazuhiro Okada , Hajime Maeda ,
Tsutomu Shin-ike , Noboru Sonoda & Nobuaki Kambe (2010) Regioselectivity of Selenium-Mediated
Carbonylation of Organolithium Compounds with Carbon Monoxide, Phosphorus, Sulfur, and Silicon and
the Related Elements, 185:5-6, 1117-1123, DOI: 10.1080/10426501003773456
To link to this article: http://dx.doi.org/10.1080/10426501003773456
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Phosphorus, Sulfur, and Silicon, 185:1117–1123, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003773456
REGIOSELECTIVITY OF SELENIUM-MEDIATED
CARBONYLATION OF ORGANOLITHIUM COMPOUNDS
WITH CARBON MONOXIDE
Shin-ichi Fujiwara,1 Akira Nishiyama,2 Kazuhiro Okada,2
Hajime Maeda,2 Tsutomu Shin-ike,1 Noboru Sonoda,2
and Nobuaki Kambe2
1Department of Chemistry, Osaka Dental University, Osaka, Japan
2Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Osaka, Japan
Regioselectivity of selenium-mediated carbonylation of organolithium compounds with car-
bon monoxide has been investigated. The reactions of lithium enolates of 2,2-dicyclohexyl
aldehyde and 1,1-dicyclohexylpropane-2-one with selenium and carbon monoxide afforded
the corresponding selenocarbonates by carbonylation at the enolate oxygen as the main prod-
uct. Carbonylation of nitrogen-containing heterocycles can give either C- or N-carbonylation
product, but diphenyl(4-pyridyno)methane, imidazole, and pyrazole afford only correspond-
ing carbamoselenoates via N-carbonylation.
Keywords Carbamoselenoates; carbon monoxide; organolithium compounds; selenium; se-
lenocarbonates; selenol esters
INTRODUCTION
We have reported selenium-mediated carbonylation of a series of organolithium
compounds with carbon monoxide1 giving rise to the corresponding selenol esters2–4 and
carbamoselenoates5 after trapping with alkyl halides. The related imidoylation by the use
of isocyanides in place of carbon monoxide has also been disclosed.6 For example, lithium
enolates of aldehydes and ketones were carbonylated to afford β-formyl and β-keto selenol
esters having 1,3-dioxoalkane units,3a,7 which are frequently encountered frameworks of
organic molecules as versatile and important functionalities in synthetic chemistry. As for
the mechanism of carbonylation of lithium enolates, we proposed a unique mechanism com-
posed of O-carbonylation and subsequent migration of the SeCO moiety to the α-carbon.
As shown in Scheme 1, reaction of enolates 1 with Se affords selenolates 2,8 which then
react with CO to give lithium selenocarbonates 4 as an initial carbonylation intermediate,
probably via formal rearrangement of 3. The detailed mechanism leading to 4 has not yet
been determined, but it may proceed stepwise with elimination of carbonyl selenide (SeCO)
Received 15 December 2008; accepted 31 December 2008.
Dedicated to Professor Naomichi Furukawa on the occasion of his 70th birthday.
Address correspondence to Shin-ichi Fujiwara, Department of Chemistry, Osaka Dental University, Hi-
rakata, Osaka 573-1121, Japan. E-mail: fujiwara@cc.osaka-dent.ac.jp and Nobuaki Kambe, Department of Ap-
plied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan. E-mail:
kambe@chem.eng.osaka-u.ac.jp
1117

1118
S. FUJIWARA ET AL.
O
O
O
O
O
OLi
R2
MeI
Se
SeLI
R1
SeMe
R1
R1
SeLi
R1
SeCO
LiSe
R3 R2
2
R3 R2
R3 R2
R3
1
7
6
CO
O
O
O
O
MeSe
O
Se
R3 R2
Li
[2,3]
MeI
R1
R2
R2
R1
R1
O
R3
R3
3
5
4
Scheme 1 Plausible mechanism.
followed by nucleophilic attack of enolate oxygen at the central carbon of SeCO9–11 or [2,3]-
rearrangement. In the cases of enolates of aldehydes, selenocarbonates 5 are obtained by
alkylation of 4 at −23◦C or below, while 4 undergoes [1,3]-rearrangement at 0◦C or above
to lithium selenocarboxylates 6 giving β-formyl selenol esters 7. However, none of the
O-carbonylation products were obtained so far from enolates of ketones and other carbonyl
compounds even at −23◦C. These results suggest that rearrangement from 4 to 6 is rapid
when R1 = H, probably due to steric repulsion between R1 and OC(O)SeLi moiety.12
In this work, we examined regioselectivity of carbonylation of lithium enolates carry-
ing bulkier substituents at the α-position(s) in order to confirm the proposed O-carbonylation
mechanism shown in Scheme 1. In addition, regioselectivity of carbonylation of some cyclic
nitrogen compounds was also examined.
RESULTS AND DISCUSSION
Carbon vs. Oxygen
We have reported that lithium enolate 1a of cyclohexanecarboxaldehyde, prepared
from the corresponding trimethylsilyl enol ether and MeLi at 20◦C, gave selenocarbonate
5a, O-carbonylation product, in 64% yield together with 16% of β-formyl selenol ester 7a,
C-carbonylation product, when treated with CO at −23◦C followed by trapping with MeI.
On the contrary, 7a was obtained selectively at 20◦C [Equation (1)].3a
1) Se (1.2 eq)
HMPA (3 eq)
temp, 30 min
2) CO (1 atm)
O
O
H
H
O
temp, time
+
(1)
H
SeMe
OLi
O
SeMe
3) MeI (2 eq)
temp, 10 min
1a
5a
7a
temp = -23 °C, time = 60 min
temp = 20 °C, time = 20 min
64%
0%
16%
59%
In order to examine the effect of substituents on the regioselectivity, we performed
carbonylation of a lithium enolate of more hindered aldehyde. Lithium enolate 1b of 2,2-
dicyclohexyl aldehyde, generated in a similar manner as that of 1a, was allowed to react
with selenium and then with carbon monoxide (1 atm) at −23◦C for 30 min.

SELENIUM-MEDIATED CARBONYLATION
1119
Selenocarbonate 5b was obtained exclusively in 93% yield after trapping with MeI
and β-formyl selenol ester 7b, C-carbonylation product, was not detected. When carbony-
lation was conducted at 20◦C for 5 h, 5b and 7b were obtained in 27% and 18% yields,
respectively.13 These results indicate that bulkier substituents at the α-position retards
isomerization of 4b, O-carbonylation intermediate, to C-carbonylation intermediate 6b
[Equation (2)].
1) Se (1.2 eq)
HMPA (3 eq)
temp, 30 min
2) CO (1 atm)
O
O
H
H
O
temp, time
+
H
SeMe
OLi
O
SeMe
(2)
3) MeI (2 eq)
temp, 10 min
1b
5b
7b
temp = -23 °C, time = 30 min
temp = 20 °C, time = 5 h
93%
27%
0%
18%
We then examined carbonylation of the corresponding lithium enolate of ketone
1c having two cyclohexyl groups at an α-carbon and found that selenocarbonate 5c
was obtained in 42% at −23◦C [Equation (3)]. This is the first example of detect-
ing O-carbonylation product from ketones rather than aldehydes and would support the
O-carbonylation mechanism shown in Scheme 1 even for ketones.14
1) Se (1.2 eq)
HMPA (3 eq)
-23 °C, 30 min
2) CO (1 atm)
-23 °C, 1 h
O
(3)
OLi
O
SeMe
3) MeI (2 eq)
-23 °C, 10 min
1c
5c, 42%
Carbon vs. Nitrogen
We have revealed that the lithio derivative of 1-pheny-1-(4-pyridino)ethane 8a is
carbonylated at benzylic carbon.2a Introduction of chlorine at the para position of the
phenyl ring (8b), which should have more acidic benzylic protons than 8a, led to the
acceleration of CO uptake and the carbonylation time was drastically shortened; however,
the yield of the product 9b was not improved [Equation (4)].15
In contrast to the reaction of 8, diphenyl-4-pyridylmethane 10 was carbonylated at
the nitrogen atom to give only carbamoselenoate 11 in 92% yield [Equation (5)] as in
the case of imidoylation.6 The corresponding carbonylation product at the central carbon
was not obtained. This regioselectivity can be explained not only by the steric factor but
also by the electron density that the anion charge of lithio-4-pyridyldiphenylmethane 12 is
localized at the nitrogen atom of the pyridyl ring.16

1120
S. FUJIWARA ET AL.
1) BuLi (1.1 eq)
3) CO (1 atm)
20 °C, time
X
X
-78 °C, 30 min
N
N
(4)
4) MeI (2 eq)
20 °C, 30 min
2) Se (1.2 eq)
HMPA (3 eq)
-78 °C,then
SeMe
O
20 °C, 30 min
8a: X = H
8b: X = Cl
9a, 35% (time = 13 h)
9b, 41% (time = 2 h)
1) BuLi (1.1 eq)
-78 °C, 30 min
N
3) CO (1 atm)
20 °C, 30 min
O
(5)
N
4) MeI (2 eq)
20 °C, 30 min
2) Se (1.2 eq)
HMPA (3 eq)
-78 °C,then
SeMe
20 °C, 30 min
11, 92%
10
Se, CO
MeI
BuLi
N
N
Li
Li
12
Regioselectivity of carbonylation of other nitrogen-containing heterocycles was also
examined. Lithio derivatives of imidazole 13, that would be present in solution as shown in
the equilibration in Figure 1, was carbonylated exclusively at nitrogen to afford carbamose-
lenoates 14 in 61% yield [Equation (6)]. Similarly, pyrazole 15 gave the corresponding
carbamoselenoate 16 as the sole product [Equation (7)].
LDA (1.1 eq)
Se (1.0 eq)
HMPA (3 eq)
1) CO (1 atm)
20 °C, 1 h
2) nBuI (2 eq)
O
N
N
NH
NH
N
(6)
(7)
SeBun
THF, -78 °C
30 min
20 °C, 30 min
13
14, 61%
N
O
N
N
SeBun
15
16, 75%
N
N
N Li
N
Li
Figure 1 Possible equilibration of lithio derivative of imidazole.

SELENIUM-MEDIATED CARBONYLATION
1121
EXPERIMENTAL
Carbonylation of lithium enolate 1b from 1-trimethylsiloxy-2,2-dicyclohexylethylene:
MeLi (1.17 M in Et2O, 1.0 mL, 1.17 mmol) was added to a THF (15 mL) solution of 1-
trimethylsiloxy-2,2-dicyclohexylethylene (1.03 mmol) at 20◦C under Ar. After 30 min, the
solution was cooled to −23◦C, selenium (1.20 mmol) and HMPA (2.96 mmol) were added,
and the mixture was kept at the same temperature for 30 min. The reaction vessel was
then purged with CO. After CO absorption ceased (30 min), MeI (2.11 mmol) was added
at the same temperature, and the mixture was warmed up to room temperature. Aqueous
saturated NH4Cl solution (100 mL) was added, and the mixture was extracted with Et2O
(50 mL). After the organic layer was dried over MgSO4, evaporation of the solvent gave a
yellow residue. Purification by PTLC using n-hexane-Et2O (20:1, v/v) yielded Se-methyl
1
O-(2,2-dicyclohexylvinyl)selenocarbonate (5b, 93%) as a pale yellow oil; H NMR (270
MHz, CDCl3): δ = 1.00–1.35 (m, 10 H), 1.35–1.90 (m, 11 H), 2.19 (brs, 1 H), 2.29 (s, 3 H),
6.87 ppm (s, 1 H); 13C NMR (68 MHz, CDCl3): δ = 6.5, 26.1, 26.8, 26.9, 30.7, 33.1, 39.3,
40.7, 131.4, 136.8, 165.4 ppm; IR (neat): = 1722 cm−1; MS (CI), m/z (relative intensity,%)
331 (M+ + 1, 62). Anal. Calcd for C16H26O2Se: C, 58.35; H, 7.96. Found: C, 58.42; H,
7.98.
Se-Methyl 2,2-Dicyclohexyl-3-oxo-selenopropionate (7b)
1
A colorless oil; H NMR (270 MHz, CDCl3): δ = 0.85–0.97 (m, 4 H), 1.07–1.30
(m, 8 H), 1.55–1.78 (m, 8 H), 2.14 (brs, 1 H), 2.29 (s, 3 H), 9.98 ppm (s, 1 H); 13C NMR
(68 MHz, CDCl3): δ = 5.1, 26.4, 26.8, 27.1, 28.0, 28.5, 40.2, 75.0, 203.2, 203.7 ppm; IR
(neat): = 1679, 1726 cm−1; MS (CI), m/z (relative intensity,%) 331 (M+ + 1, 26). Anal.
Calcd for C16H26O2Se: C, 58.35; H, 7.96. Found: C, 58.74; H, 8.12.
Se-Methyl 1-(p-Chlorophenyl)-1-(4-pyridyl)ethane-1-selenocarboxylate
(9b)
1
A yellow oil; H NMR (270 MHz, CDCl3): δ = 1.99 (s, 3 H), 2.21 (s, 3 H), 7.14
(d, J = 6.4 Hz, 2 H), 7.19 (d, J = 8.8 Hz, 2 H), 7.32 (d, J = 8.8 Hz, 2 H), 8.56 ppm (d,
J = 6.4 Hz, 2 H); 13C NMR (68 MHz, CDCl3): δ = 6.5, 26.0, 64.3, 123.2, 128.5, 130.2,
134.1, 140.0, 149.9, 152.2, 206.0 ppm; IR (neat): = 1682 cm−1; MS (CI), m/z (relative
intensity,%) 340 (M+ + 1, 100). HRMS (CI) Calcd for C15H15ClNOSe: 340.0008. Found:
340.0008.
Se-Methyl 4-(Diphenylmethylidene)-4H-azine-N-selenocarbamate (11)
A yellow oil; 1H NMR (270 MHz, CDCl3): δ = 2.35 (s, 3 H), 6.16 (d, J = 8.8 Hz,
2 H), 7.15–7.32 pm (m, 12 H); 13C NMR (68 MHz, CDCl3): δ = 6.8, 114.0, 123.6,
126.3, 126.8, 128.2, 129.0, 13.2, 141.8, 162.7 ppm; IR (neat): = 1650 cm−1; MS (CI), m/z
(relative intensity,%) 367 (M+ + 1, 50). HRMS (EI) Calcd for C20H17NOSe: 367.0475.
Found: 367.0483.
Se-n-Butyl Imidazole-1-carboselenolate (14)
A pale brown oil; 1H NMR (270 MHz, CDCl3): δ = 0.96 (t, J = 7.3 Hz, 3 H), 1.46
(sext, J = 7.3 Hz, 2 H), 1.80 (quint, J = 7.3 Hz, 2 H), 3.19 (t, J = 7.3 Hz, 2 H), 7.11 (s,

1122
S. FUJIWARA ET AL.
1 h), 7.44 (s, 1 H), 8.17 pm (s, 1 H); 13C NMR (68 MHz, CDCl3): δ = 13.4, 22.9, 27.9, 32.1,
116.0, 131.0, 135.4, 164.4 ppm; IR (neat): = 1689 cm−1; MS (EI), m/z (relative intensity,%)
232 (M+, 10). Anal. Calcd for C8H12N2OSe: C, 41.56; H, 5.24; N, 12.12. Found: C, 41.29;
H, 5.41; N, 11.94.
Se-n-Butyl Pyrazole-1-carboselenolate (16)
A yellow oil; 1H NMR (270 MHz, CDCl3): δ = 0.95 (t, J = 7.3 Hz, 3 H), 1.46 (sext,
J = 7.3 Hz, 2 H), 1.76 (quint, J = 7.3 Hz, 2 H), 3.04 (t, J = 7.3 Hz, 2 H), 6.48 (s, 1 h), 7.73
(s, 1 H), 8.14 pm (s, 1 H); 13C NMR (68 MHz, CDCl3): δ = 13.5, 22.9, 25.4, 32.4, 109.8,
126.8, 143.8, 168.7 ppm; IR (neat): = 1692 cm−1; MS (EI), m/z (relative intensity,%) 232
(M+, 17). Anal. Calcd for C8H12N2OSe: C, 41.56; H, 5.24; N, 12.12. Found: C, 41.69; H,
5.34; N, 11.98.
REFERENCES
1. For reviews of carbonylation, see: (a) H. M. Colquhoun, D. J. Thompson, and M. V. Twigg,
Carbonylation: Direct Synthesis of Carbonyl Compounds (Plenum Press, New York, 1991);
(b) E. W. Abel, F. G. A. Stone, and G. Wilkinson, Eds., Comprehensive Organometallic Chemistry
(Pergamon Press, Oxford, 1995), vol. 12; (c) L. Kolla´r, Ed., Modern Carbonylation Method
(Wiley-VCH, Weinheim, Germany, 2008).
2. Carbonylation of lithio derivatives of hydrocarbons, see: (a) H. Maeda, S. Fujiwara, T. Shin-ike,
N. Kambe, N. Sonoda, J. Am. Chem. Soc., 118, 8160 (1996); (b) H. Maeda, S. Fujiwara, A.
Nishiyama, T. Shin-ike, N. Kambe, and N. Sonoda, Synlett, 342 (1997).
3. For carbonylation of lithium enolates of ketones and aldehydes, see (a) S. Fujiwara, A. Nishiyama,
T. Shin-ike, N. Kambe, and N. Sonoda, Org. Lett., 6, 453 (2004); for that of amides and esters,
(b) N. Kambe, A. Nishiyama, S. Fujiwara, T. Shin-ike, and N. Sonoda, Phosphorus, Sulfur, and
Silicon, 180, 1001 (2005).
4. For a recent review on selenol esters: S. Fujiwara and N. Kambe, In Topics in Current Chemistry
251: Chalcogen Carboxylic Acid Derivatives, S. Kato, Ed. (Springer, Berlin, 2005), pp. 87–141.
5. N-Carbonylation of lithium azaenolates of amides, formamides, ureas, and carbamates:S. Fuji-
wara, K. Okada, Y. Shikano, Y. Shimizu, T. Shin-ike, J. Terao, N. Kambe, and N. Sonoda, J. Org.
Chem., 72, 273 (2007).
6. Imidoylation of lithio derivatives of hydrocarbons:S. Fujiwara, H. Maeda, T. Matsuya, T. Shin-
ike, N. Kambe, and N. Sonoda, J. Org. Chem., 65, 5022 (2000).
7. There are only a few other reports for 1,3-dioxoalkanes involving a selenol ester unit(s).
(a) E. Ziegler and E. No¨lken, Monatsh., 89, 737 (1958); Chem. Abstr., 53, 12284d (1959);
(b) A. Ruwet, A. Pourveur, and M. Renson, Bull. Soc. Chim. Belg., 79, 631 (1970); Chem. Abstr.,
74, 53431a (1971); (c) S. Kim and S. Y. Jon, J. Chem. Soc., Chem. Commun., 1335 (1996).
8. Liotta and co-workers reported that α-alkylselenoketones were obtained by the reaction of
lithium enolates of ketones with selenium in the presence of additives such as HMPA followed
by trapping with alkyl halides; however, the yields were very low without additives: (a) D. Liotta,
G. Zima, C. Barnum, and M. Saindane, Tetrahedron Lett., 21, 3643 (1980); (b) K. Swiss, W.-B.
Choi, J. Mohan, C. Barum, M. Saindane, G. Zima, and D. Liotta, Heteroatom Chem., 1, 141
(1990).
9. Theoretical study on generation of carbonyl selenide (SeCO):W. F. de Souza, N. Kambe, and N.
Sonoda, Chem. Lett., 25, 155 (1996).
10. We already examined the reaction of isoselenocyanate, having isoelectronic structure with SeCO,
with organolithium compounds focusing on the siteselectivities. Phenyllithium attacked selenium

SELENIUM-MEDIATED CARBONYLATION
1123
exclusively, whereas lithium enolate of a ketone reacted with SeCO at both its C- and O-
nucleophilic centers attacking the central carbon of SeCO:H. Maeda, N. Kambe, N. Sonoda, S.
Fujiwara, and T. Shin-ike, Tetrahedron, 52, 12165 (1996).
11. For carbophilic addition of organocopper reagents to SeCO:S. Fujiwara, A. Asai, T. Shin-ike, N.
Kambe, and N. Sonoda, J. Org. Chem., 63, 1724 (1998).
12. Theoretical study on structure, bonding, and aggregation of organolithium compounds shown in
Scheme 1:L. M. Pratt, S. Fujiwara, and N. Kambe, Tetrahedron, 65, 1017 (2009).
13. 2,2-Dicyclohexyl aldehyde was recovered in 32% yield. This indicated that deselenocarboxyla-
tion from 4b and/or 6b might proceed at 20◦C.
14. The parent ketone and α-selenoketone were detected as byproducts.
15. About 30% of 8b was recovered.
16. (a) S. Bank and R. Dorr, J. Org. Chem., 52, 501 (1987); (b) S. Bank and M. Gernon, J. Org.
Chem., 52, 5105 (1987).