Regioselective addition reactions of propargyl bromides to carbonyl compounds with gallium catalyzed by indium

Article abstract of DOI:10.1002/adsc.200505046

Reactions of organogallium reagents generated from propargyl bromides having substituents at the γ-position and gallium in the presence of 5 mol % of indium with aldehydes and ketones selectively produced homoallenyl alcohols in good to excellent yields.

Full text of DOI:10.1002/adsc.200505046

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Regioselective Addition Reactions of Propargyl Bromides to
Carbonyl Compounds with Gallium Catalyzed by Indium
Phil Ho Lee,* Hyun Kim, Kooyeon Lee
Department of Chemistry, Kangwon National University, Chunchon 200-701, Republic of Korea
Fax: (þ82)-33-253-7582, e-mail: phlee@kangwon.ac.kr
Received: January 25, 2005; Accepted: April 15, 2005
Abstract: Reactions of organogallium reagents gen-
erated from propargyl bromides having substituents
at the g-position and gallium in the presence of
5 mol % of indium with aldehydes and ketones selec-
tively produced homoallenyl alcohols in good to ex-
cellent yields. Treatment of organogallium reagents
obtained from propargyl bromide or propargyl bro-
mides having substituents at the a-position and galli-
um in the presence of 5 mol % of indium with car-
bonyl compounds selectively afforded homoproparg-
yl alcohols.
Scheme 1.
Keywords: allenylation; gallium; indium; propargyla-
tion; regioselectivity
tuted propargyl bromides led us to investigate the effi-
cient and regioselective, indium-catalyzed addition re-
actions of propargyl bromides to carbonyl compounds
with gallium (Scheme 1).
Selective nucleophilic allenylations or propargylations
First, the reactivity and regioselectivity of a variety of
to carbonyl compounds in the syntheses of either homo- organogallium reagents derived from propargyl bro-
allenyl alcohols or homopropargyl alcohols are a very mide and 3-bromo-1-(trimethylsilyl)-1-propyne were
important class of organic transformations.[1] To date examined in the reactions with benzaldehyde and their
various methods have been developed on the basis of results were compared to references (Table 1). Al-
the nucleophilic character of propargylmetal species ob- though the propargylindium reagent gave addition
tained from propargyl halides and metals (Ti, Al, Si, Sc, products in 72% yield (a:g¼86:14) in H2O-MeOH (en-
In, Sn, Zn, Bi, Cd, and Sb).[1,2] Recently, a reagent de- try 3), gallium reagents in aqueous media were not ef-
rived from the treatment of 3-bromo-1-(trimethyl- fective to produce the desired products (entries 1, 2, 4,
silyl)-1-propyne with Ga/KI/LiCl in THF selectively and 5). Organogallium reagent generated from proparg-
gave propargyl products in the reaction with carbonyl yl bromide and gallium in THF did not afford the addi-
compounds.[3] The selective preparations of either the tion product (entry 7). However, the use of 1 equivalent
homoallenyl alcohols or homopropargyl alcohols using of gallium with 5 mol % of indium (THF, 258C, 1 h) re-
cat-In/InX3 (X¼Fand Br)-mediated reactions of 3-bro- gioselectively gave homopropargyl alcohol in 96% yield
mo-1-(trialkylsilyl)-1-propynes with various aldehydes (a:g¼100:0) (entry 9),[11] whereas the propargylindi-
were reported.[4] Surprisingly, although organoindium um reagent afforded the addition products in 94% yield
reagents obtained from the reaction of indium with allyl (a:g¼84:16) in THF at 258C for 2 h (entry 6) and the
halides, allyl acetates, and propargyl halides have been propargylgallium reagent produced the desired prod-
used extensively in carbonyl addition reactions,[5] addi- ucts in 90% yield (a:g¼ >99:1) in THF at 678C for
[6]
tions to C C multiple bonds and nitriles, and cross- 4 h (entry 11).[3b] Although 10 mol % and 1 mol % indi-
ꢀ
coupling reactions,[7] organogallium reagents prepared um selectively furnished the homopropargyl alcohol,
from gallium and allyl halides and propargyl halides the desired product was produced in moderate yields
have not been explored to a great extent in organic syn- (74% and 77%, respectively) (entries 8 and 10). The
theses.[8] The preparation of allylgalliums via direct re- use of DMFas a solvent and application of ultrasonic ir-
duction of allylic bromides using a catalytic amount of radiation in DMF failed to generate addition products
indium[9] and selective allene formation[7i,10] using orga- (entries 12 and 13). When 3-bromo-1-(trimethylsilyl)-
noindium reagents generated from indium and g-substi- 1-propyne was used, organoindium (entry 16) and orga-
Adv. Synth. Catal. 2005, 347, 1219–1222
DOI: 10.1002/adsc.200505046
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Phil Ho Lee et al.
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Table 1. Reaction optimization.[a]
Table 2. Regioselectivity comparison of cat-In/Ga with Ga/
KI/LiCl.
demonstrate the efficiency and scope of the present
methods. The results are summarized in Table 3. For
the propargyl bromide as precursor of the nucleophile,
both aliphatic and aromatic aldehydes selectively gave
homopropargyl alcohols via a-attack in good to excel-
lent yields (entries 1, 4, 6, 12, 14, 17 and 18). Contrary
to the reaction of propargyl bromide, the reactions of
propargyl bromides having various alkyl and aryl sub-
stituents at the g-position with aldehydes and ketones
produced homoallenyl alcohols as a major product (en-
tries 2 and 3, 5, 7–9, 15 and 16, 19, and 22). Although in-
troduction of a methyl group at the g-position of the or-
ganogallium reagents obtained from propargyl bromide
and Ga/KI/LiCl dramatically reduced the regioselectiv-
ity (n-C9H19CHO; a:g¼ >99:1 to 58:42, C6H11CHO;
a:g¼ >99:1 to 48:52),[3b] the present conditions gave
regioselectively reversed homoallenyl alcohols (entry 1
vs. 2 and entry 3 vs. 4, Table 2).
A methyl substituent at the g-position afforded better
selectivity than ethyl and phenyl groups (entries 7–9).
However, the organogallium reagent derived from galli-
um and 3-bromo-1-(trimethylsilyl)-1-propyne selective-
ly gave rise to homopropargyl alcohols, albeit with the g-
trimethylsilyl substituent (entries 10 and 23). Under the
present conditions, the reaction of 4-methoxybenzalde-
hyde with 1-bromo-2-butyne exceptionally produced
the propargyl alcohol in 82% yield even with g-methyl
substituent (entry 13). Variation of electron density on
the aromatic rings did not diminish the efficiency and se-
lectivity (entries 12–17). A hydroxy group is tolerated
on the benzaldehyde (entry 17). The organogallium re-
[a]
Reactions of the Grignard-type performed in the presence
of 1 equivalent of metal (In or Ga), 1.0 equivalent of ben-
zaldehyde, and 2.0 equivalents of propargyl bromide in
solvent (0.3 M) at 258C. 0% yield means that both
Grignard-and Barbier-type reactions did not proceed.
Yield of isolated product. Ratios were obtained on the ba-
sis of an internal standard (dodecane) in GC.
[b]
[c]
5 mol % of In and 1 equiv. of Ga were used.
[d]
Ref.[2k]
[e]
Ratio of H2O to MeOH¼2: 1.
[f]
10 mol % of In and 1 equiv. of Ga were used.
[g]
1 mol % of In and 1 equiv. of Ga were used.
[h]
Ref.[3b]
[i]
Ultrasonic irradiation was used.
[j]
Ref.[2h]
[k]
This reaction proceeded in a Barbier-type manner.
[l]
Ref.[4]
[m] Ref.[3a]
nogallium reagents (entry 18) in the presence of agent derived from 3-bromo-1-butyne having a a-meth-
5 mol % of indium gave the same results in yield yl substituent selectively afforded a homopropargyl al-
(81%) and selectivity (a-attack). The organogallium re- cohol, which is clearly different from the g-selectivity
agent derived from gallium and 3-bromo-1-(trimethyl- of 1-bromo-2-butyne having a g-methyl substituent (en-
silyl)-1-propyne did not produce the addition product tries 11 and 7). A similar trend of reactivity and regiose-
in THF (entry 17).
lectivity was obtained from the reactions ofaliphatic and
We applied the optimum conditions (cat-In/Ga/THF) aromatic ketones with organogallium reagents in the
to various propargyl halides and carbonyl compounds to presence of 5 mol % of indium (entries 19–24).
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Regioselective Addition of Propargyl Bromides to Carbonyl Compounds
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Table 3. Reactions of propargyl bromides with carbonyl com-
pounds with cat-In/Ga.[a]
Scheme 2. Competition reaction of benzaldehyde and aceto-
phenone and acetophenone and 4-phenyl-2-butanone under
the present conditions.
position and gallium in the presence of 5 mol % of indi-
um with aldehydes and ketones selectively produced ho-
moallenyl alcohols in good to excellent yields. However,
treatment of organogallium reagents obtained from
propargyl bromide or propargyl bromides having sub-
stituents at the a-position and gallium in the presence
of 5 mol % of indium with carbonyl compounds selec-
tively afforded homopropargyl alcohols. Because orga-
nogallium reagents generated in situ from propargyl
bromides and gallium with cat-indium were not previ-
ously applied to metal-catalyzed organic reactions, these
results should provide more opportunities for the dis-
[a]
Reactions of the Grignard-type performed in the presence
of 5 mol % of In, 1.0 equivalent of carbonyl compound,
2.0 equivalents of propargyl bromide, and 1.0 equivalent
of Ga in THF (0.3 M).
Yield of isolated product. Ratios were obtained on the ba-
sis of an internal standard (dodecane) in GC.
Reactions proceeded in Barbier-type manner.
ꢀ
covery of efficient and selective C C bond-forming re-
actions. Further studies to explain the utility and mech-
anism of this reaction are in progress.
[b]
[c]
Experimental Section
Typical Experimental Procedure
To investigate the reactivity of aromatic aldehydes
and ketones toward organogallium reagents, an excess
of a mixture of benzaldehyde and acetophenone was
To a solution of a catalytic amount of indium powder (5.7 mg,
5 mol %) and gallium ingots (69.7 mg, 1.0 mmol, cut into small
treated with the propargylgallium reagent in the pres- pieces) in THF (3 mL) was added propargyl bromide
(237.9 mg, 2.0 mmol) under a nitrogen atmosphere at 108C.
After the gallium ingot had dissolved for 1 h at 108C, benzalde-
hyde (106.1 mg, 1.0 mmol) was added to the reaction mixture.
After being stirred at 258C for 1 h, the reaction mixture was
poured into aqueous saturated NaHCO3 (20 mL). The aqueous
layer was extracted with ether (3ꢁ5 mL) and the combined or-
ganic layers were washed with brine (20 mL), dried with
MgSO4, filtered, and concentrated under vacuum. The residue
was purified by silica gel column chromatography (n-hexane/
EtOAc¼7/1) to give 1-phenyl-3-butyn-1-ol; yield: 141.0 mg
(96%).
ence of 5 mol % of indium, producing chemoselectively
1-phenyl-3-butyn-1-ol in 75% yield (Scheme 2). Expo-
sure of an excess of a mixture of acetophenone and 4-
phenyl-2-butanone with the propargylgallium reagent
gave 6-phenyl-1-hexyn-4-ol in 58% yield and 6-phenyl-
1,2-hexadien-4-ol in 14% yield. These results mean
that the relative order of reactivity of carbonyl com-
pounds toward organogallium reagents in the presence
of 5 mol % of indium is aromatic aldehyde>aliphatic
ketone>aromatic ketone.
In conclusion, we have demonstrated the efficient and
regioselective addition reactions of propargyl bromides
to carbonyl compounds with gallium catalyzed by indi-
um. Reactions of organogallium reagents generated
from propargyl bromides having substituents at the g-
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Phil Ho Lee et al.
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Acknowledgements
ta, H. Yamamura, M. Kawai, Org. Lett. 2000, 2, 847;
h) K. K. Chauhan, C. G. Frost, J. Chem. Soc. Perkin
Trans. 1 2000, 3015; i) A. N. Pae, Y. S. Cho, Curr. Org.
Chem. 2002, 6, 715; j) J. Podlech, T. C. Maier, Synthesis
2003, 633; k) T.-S. Jang, G. Keum, S. B. Kang, B. Y.
Chung, Y. Kim, Synthesis 2003, 775; l) T. Hirashita, S.
Kambe, H. Tsuji, H. Omori, S. Araki, J. Org. Chem.
2004, 69, 5054.
This work was supported by Grant No. R02-2003-000-10023-0
of the Basic Research Program of the Korea Science & Engi-
neering Foundation and the CMDS at KAIST. The NMR and
mass data were obtained from the central instrumental facility
in Kangwon National University.
[6] a) B. C. Ranu, A. Majee, Chem. Commun. 1997, 1225;
b) N. Fujiwara, Y. Yamamoto, J. Org. Chem. 1997, 62,
2318; b) N. Fujiwara, Y. Yamamoto, J. Org. Chem.
1999, 64, 4095; c) P. H. Lee, S. Kim, K. Lee, D. Seomoon,
H. Kim, S. Lee, M. Kim, M. Han, K. Noh, T. Living-
house, Org. Lett. 2004, 6, 4825; d) P. H. Lee, Y. Heo, D.
Seomoon, S. Kim, K. Lee, Chem. Commun. 2005, 1874.
[7] a) I. Perez, J. P. Sestelo, L. A. Sarandeses, Org. Lett.
1999, 1, 1267; b) D. Gelman, H. Schumann, J. Blum, Tet-
rahedron Lett. 2000, 41, 7555; c) P. H. Lee, S.-Y. Sung, K.
Lee, Org. Lett. 2001, 3, 3201; d) I. Perez, J. P. Sestelo,
L. A. Sarandeses, J. Am. Chem. Soc. 2001, 123, 4155;
e) T. Hirashita, H. Yamamura, M. Kawai, S. Araki,
Chem. Commun. 2001, 387; f) K. Takami, H. Yorimitsu,
H. Shnokubo, S. Matsubara, K. Oshima, Org. Lett.
2001, 3, 1997; g) M. A. Pena, I. Perez, J. P. Sestelo,
L. A. Sarandeses, Chem. Commun. 2002, 2246; h) K.
Lee, J. Lee, P. H. Lee, J. Org. Chem. 2002, 67, 8265;
i) K. Lee, D. Seomoon, P. H. Lee, Angew. Chem. Int.
Ed. 2002, 41, 3901; j) T. Hirashita, Y. Hayashi, K. Mitsui,
Araki, S. J. Org. Chem. 2003, 68, 1309; k) U. Lehmann, S.
Awasthi, T. Minehan, Org. Lett. 2003, 5, 2405; l) P. H.
Lee, S. W. Lee, K. Lee, Org. Lett. 2003, 5, 1103;
m) M. A. Pena, J. P. Sestelo, L. A. Sarandeses, Synthesis
2003, 780; n) P. H. Lee, S. W. Lee, D. Seomoon, Org.
Lett. 2003, 5, 4963; o) S. W. Lee, K. Lee, D. Seomoon,
S. Kim, H. Kim, H. Kim, E. Shim, M. Lee, S. Lee, M.
Kim, P. H. Lee, J. Org. Chem. 2004, 69, 4852; p) P. H.
Lee, D. Seomoon, K. Lee, Org. Lett. 2005, 7, 343.
[8] a) S. Araki, H. Ito, Y. Butsugan, Appl. Organomet.
Chem. 1988, 2, 475; b) S.-I. Usugi, H. Yorimitsu, K. Osh-
ima, Tetrahedron Lett. 2001, 42, 4535; c) Z. Wang, S.
Yuan, C.-J. Li, Tetrahedron Lett. 2002, 43, 5097; d) T.
Tsuji, S.-I. Usugi, H. Yorimitsu, H. Shinokubo, S. Matsu-
bara, K. Oshima, Chem. Lett. 2002, 2; e) V. Nair, S. Ros,
C. N. Jayan, B. S. Pillai, Tetrahedron 2004, 60, 1959; f) M.
Yamaguchi, in: Main Group Metals in Organic Synthesis;
(Eds.: H. Yamamoto, K. Oshima), Wiley-VCH, Wein-
heim, 2004, Vol. 1, pp. 307–322; g) P. C. Andrew, A. C.
Peatt, C. L. Raston, Tetrahedron Lett. 2004, 45, 243.
[9] K. Takai, Y. Ikawa, Org. Lett. 2002, 4, 1727.
References and Notes
[1] a) J. S. Panek, in: Comprehensive Organic Synthesis,
(Ed.: S. L. Schreiber), Pergamon Press, Oxford, 1991,
Vol. 1, p. 595; b) H. Yamamoto, in: Comprehensive Or-
ganic Synthesis, (Ed.: C. H. Heathcock), Pergamon Press,
Oxford, 1991, Vol. 2, Chapter 1.3, pp. 81–98; c) Y. Yama-
moto, N. Asao, Chem. Rev. 1993, 93, 2207; d) M. Yama-
guchi, in: Main Group Metals in Organic Synthesis,
(Eds.: H. Yamamoto, K. Oshima), Wiley-VCH, Wein-
heim, 2004, Vol. 1, pp. 307–322.
[2] a) R. G. Daniels, L. A. Paquette, Tetrahedron Lett. 1981,
22, 1579; b) M. Ishiguro, N. Ikeda, H. Yamamoto, J. Org.
Chem. 1982, 47, 2227; c) J. Nokami, T. Tamaoka, T. Ko-
guchi, R. Okawara, Chem. Lett. 1984, 1939; d) R. W.
Hoffmann, J. Lanz, R. Metternich, G. Tarara, D. Hoppe,
Angew. Chem. Int. Ed. 1987, 26, 1145; e) M. Suzuki, Y.
Morita, R. Noyori, J. Org. Chem. 1990, 55, 441; f) L.-J.
Zhang, Y.-Z. Huang, Z.-H. Huang, Tetrahedron Lett.
1991, 32, 6579; g) L.-J. Zhang, X.-S. Mo, J.-L. Huang,
Y.-Z. Huang, Tetrahedron Lett. 1993, 34, 1621; h) M. B.
Isaac, T.-H. Chan, Chem. Commun. 1995, 1003; i) S.
Doherty, J. F. Corrigan, A. J. Carter, Adv. Organomet.
Chem. 1995, 37, 39; j) J. Tsuji, T. Mandai, Angew.
Chem. Int. Ed. 1995, 34, 2589; k) X.-H. Yi, Y. Meng,
X.-G. Hua, C.-J. Li, J. Org. Chem. 1998, 63, 7472;
l) J. A. Marshall, N. D. Adams, J. Org. Chem. 1999, 64,
5201; m) S. E. Denmark, T. Wynn, J. Am. Chem. Soc.
2001, 123, 6199; n) D. A. Evans, Z. K. Sweeney, T. Rovis,
J. S. Tedrow, J. Am. Chem. Soc. 2001, 123, 12095; o) L. R.
Reddy, H.-J. Gais, C.-W. Woo, G. Raabe, J. Am. Chem.
Soc. 2002, 124, 10427; p) W. Miao, T.-H. Chan, Synthesis
2003, 785; q) T.-P. Loh, M.-J. Lin, K.-L. Tan, Tetrahedron
Lett. 2003, 44, 507; r) W. Miao, L. W. Chung, Y. D. Wu,
T. H. Chan, J. Am. Chem. Soc. 2004, 126, 13326.
[3] a) Y. Han, Y.-Z. Huang, Tetrahedron Lett. 1994, 35, 9433;
b) Y. Han, Z. Chi, Y.-Z. Huang, Synth. Commun. 1999,
29, 1287.
[4] M.-J. Lin, T.-P. Loh, J. Am. Chem. Soc. 2003, 125, 13042.
[5] a) C.-J. Li, Chem. Rev. 1993, 93, 2023; b) P. Cintas, Synlett
1995, 1087; c) C.-J. Li, Tetrahedron 1996, 52, 5643; d) C.-J.
Li, T.-H. Chan, Organic Reactions in Aqueous Media,
Wiley, New York, 1997; e) C.-J. Li, T.-H. Chan, Tetrahe-
dron 1999, 55, 11149; f) G. Babu, P. T. Perumal, Aldrichi-
mica Acta 2000, 33, 16; g) S. Araki, T. Kamei, T. Hirashi-
[10] a) K. Lee, H. Kim, T. Miura, K. Kiyota, H. Kusama, S.
Kim, N. Iwasawa, P. H. Lee, J. Am. Chem. Soc. 2003,
125, 9682.
1222
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Adv. Synth. Catal. 2005, 347, 1219–1222