Synthesis of butyrolactones by nickel-catalyzed reductive cyanation of alkynols in water

Article abstract of DOI:10.1016/j.tetlet.2004.12.019

One-pot catalytic synthesis of butyrolactones from alkynols under mild conditions is described here. The methodology involves the use of the K ₂[Ni(CN)₄]/NaBH₄ system in presence of KCN and water. According to the experimental evidences, a possible mechanism pathway is suggested, which involves the nickel-catalyzed reductive cyanation of alkynol, followed by nitrile hydration, reduction of double bond and lactonization.

Full text of DOI:10.1016/j.tetlet.2004.12.019

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 803–805
Synthesis of butyrolactones by nickel-catalyzed reductive
cyanation of alkynols in water
a,
Jos e´ Luis Garc ´ı a Guti e´ rrez, Federico Jim e´ nez-Cruz and No e´ Rosas Espinosa
a
b
*
a
Instituto Mexicano del Petr o´ leo. Eje Central L a´ zaro C a´ rdenas 15, M e´ xico DF 07730, M e´ xico
b
Instituto de Qu ı´ mica, Universidad Nacional Aut o´ noma de M e´ xico, Circuito Exterior,
Ciudad Universitaria, M e´ xico DF 04510, M e´ xico
Received 13 August 2004; revised 29 November 2004; accepted 3 December 2004
Available online 19 December 2004
Abstract—One-pot catalytic synthesis of butyrolactones from alkynols under mild conditions is described here. The methodology
involves the use of the K [Ni(CN) ]/NaBH system in presence of KCN and water. According to the experimental evidences, a pos-
2
4
4
sible mechanism pathway is suggested, which involves the nickel-catalyzed reductive cyanation of alkynol, followed by nitrile hydra-
tion, reduction of double bond and lactonization.
ꢀ
2004 Elsevier Ltd. All rights reserved.
Lactones have deserved great interest in synthetic and
natural products chemistry. These structures occur
extensively in the natural world and their biological
and pharmacological activities have been widely stud-
a-ketoalkynes affords substituted 2,4-dioxopyrido[2,3-
d]pyrimidines derivatives. Recently, the syntheses of
9
substituted 1,8-naphthyridines and 2H-pyrano[3,2-
g]quinolin-2-ones was carried out by the reaction of
a-ketoalkynes with 6-aminonicotinamide and 7-amino-
4-methyl-coumarin, respectively, by using the nickel sys-
1
ied. Several synthetic methods for lactones have been
1
,2
developed and reported during these last years. A con-
siderable number of these synthetic methods involves
transition metal complexes as catalysts to accomplish
the formation of carbon–carbon bonds by activation
of unsaturated hydrocarbons by carbon monoxide and
1
0
tem before indicated. In this context, we wish to report
the catalytic synthesis of butyrolactones from alkynols
in good yield by the K [Ni(CN) ]/NaBH system, using
2
4
4
an stoichiometric amount of KCN in water.
3
,4
cyanide. In seeking to develop new synthetic methods
for heterocyclic organic compounds by using a novel
nickel-based catalytic procedure, we have shown that
a-ketoalkynes can be carbonylated in the presence of
In Table 1 is showed the results of catalytic cyanation of
alkynols with K [Ni(CN) ]/NaBH /KCN system in
2
4
4
1
1
water (see Scheme 1). The 2,4-disubstituted-4-butyro-
lactones synthesis is carried out in good yield. It was ob-
served that in absence of either K [Ni(CN) ] or NaBH
4
Ni(CN) and carbon monoxide and basic aqueous med-
2
ium under phase transfer conditions to give unsaturated
5
2
4
hydroxybutyrolactones. In addition, it was possible to
obtain unsaturated hydroxybutyrolactams by working
the same catalyst precursor in the presence of excess cya-
the reaction is not carried out and in the presence of
internal alkynols a mixture of several product is
obtained.
6
,7
nide ions and aqueous phase. Subsequently, it was re-
ported the cascade conversion of propargyl halides or
alcohols into 4,6-dimethyl-5-cyano-2-pyrone catalyzed
Likewise, NiCl can act as precursor of active specie
2
(Table 1, entry lc). The butyrolactone structures indicate
that the cyanide anion is added on the internal acetyl-
enic carbon. In addition, results of this reaction with
1-phenylhex-1-yn-3-one (1f) conducted to 2-phenyl-4-
propyl-4-butyrolactone and the 4-keto-2-phenylhepta-
by Ni(CN) in presence of carbon monoxide and cya-
2
8
nide ions in water. Likewise, it was shown that the reac-
tion of 6-amino-1,3-dimethyluracil with substituted
1
4
noic acid. A lower yield of lactone is obtained when
the substrate presents a keto group instead of alcohol
group into its structure. This could be due to the lower
Keywords: Alkynol; Lactone; Nickel; Cyanide; Borohydride; Cyana-
tion; Catalysis.
*
Corresponding author. Tel.: +52 55 9175 6646; fax: +52 55 9175
429; e-mail: garciajl@imp.mx
amount of NaBH used in the experimental conditions,
4
which limited the reduction of the keto group and the
8
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.12.019

804
J. L. Garc ı´ a Guti e´ rrez et al. / Tetrahedron Letters 46 (2005) 803–805
Table 1. Synthesis of butyrolactones from alkynols
Entry
Substrate
Entry
Product
% Yield
1
1
1
1
1
1
1
1
a
b
c
c
d
e
f
3-Butyn-1-ol
4-Pentyn-2-ol
2a
2b
2c
2c
2d
2e
2f
2-Methyl-4-butyrolactone
74
87
93
2,4-Dimethyl-4-butyrolactone
4-Ethyl-2-methyl-4-butyrolactone
4-Ethyl-2-methyl-4-butyrolactone
2-Methyl-4-propyl-4-butyrolactone
2-Hydroxymethyl-4-butyrolactone
2-Phenyl-4-propyl-4-butyrolactone
4-Keto-2-phenylheptanoic acid
5-Hexyn-3-ol
5-Hexyn-3-ol
6-Heptyn-4-ol
a
95
85
b
2-Butyne-1,4-diol
1-Phenyl-hex-1-yn-3-one
1-Phenyl-hex-1-yn-3-one
58
5
c
c
d
f
2g
89
a
b
c
2
NiCl was used.
Sample contained hydroxycarbonyl products; the ratio of lactone:hydroxycarbonyl product was about 1:1.
a-Ketoalkyne was used.
Isolated from the first extraction with ether.
d
R
R
1
) K [Ni(CN) ]/NaBH /KCN
2
4
4
R'
2
) H+
HO
O
R'
O
Scheme 1.
1
9
subsequent lactonization. It is also noted that during the
cyanide addition a double bond is formed, which is re-
duced before the lactonization.
mechanism pathway. It is possible that the nickel also
catalyze the hydration of the nitrile to 2,3-unsaturated
2
0
acid, specie 5, as the triple bond case. The before step
is followed by a double bond reduction with NaBH to
4
According to prior observations, a series of successive
steps is suggested: reduction of alkynol, cyanation,
hydration of the nitrile group, reduction of double bond
and lactonization (see Scheme 2). It is know that several
Ni(II) salts, that is, chloride and cyanide, in the presence
give the respective 4-hydroxy acid. Lactonization of this
latter specie gives the butyrolactone. Finally, the tetracy-
anonickel(II) (specie 1) is regenerated by the oxidation
of the tetracyanonickel(0) (specie 6) with water accord-
1
5
ing to the literature.
1
5
of excess cyanide ions in water generates the specie 1.
This specie can react with an alkyne by the displacement
of cyanide ions to give the specie 2. In this way the acti-
vated alkyne, by its p-coordination at the nickel atom, is
susceptible to a nucleophilic addition of hydride specie.
Subsequently, the formed r-vinyl complex, specie 3, can
undergo a reductive elimination to give the specie 4. In
recently publications, the Ni(0) fragment [(dippe)Ni]
has been found to p-coordinate to the CN bond of sev-
eral organic nitriles and undergo reversible insertion
In conclusion, a novel and simple method for the cata-
lytic synthesis of 2,4-disubstitutedbutyrolactones is re-
ported. It is suggested that the reaction is catalyzed by
cyanonickel(II) specie, which is regenerated via its re-
oxidation with water. Apparently, the key step in the
process is the reductive elimination of the cyanide and
the vinyl attached on nickel atom. The preparation of
butyrolactones by this method can apply to a-ketoalky-
nes as substrates.
1
6–18
into the R–CN bond. Thus, a interconversion be-
tween the species 3 and 4 should be consider in the
Acknowledgments
The authors are indebted to Roc ´ı o Pati n˜ o, H e´ ctor R ´ı os-
Olivares, Georgina Espinosa R. Alfredo Toscano and
Sim o´ n Hern a´ ndez-Ortega for their technical assistance.
References and notes
1. Picman, A. K. Biochem. Syst. Ecol. 1986, 14, 255.
2. Collins, I. J. Chem. Soc., Perkin Trans. 1 1999, 1396.
3. Cornils, B.; Herrmann, W. A. Applied Homogeneous
Catalysis with Organometallic Compounds; VCH: New
York, 1996.
4
. Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V.
Carbonylation: Direct Synthesis of Carbonyl Compounds;
Plenum: New York, 1991.
5
. Arzoumanian, H.; Nuel, D.; Jean, M.; Cabrera, A.;
Garcia, J. L.; Rosas, N. Organometallics 1995, 14, 5438.
Scheme 2.

J. L. Garc ı´ a Guti e´ rrez et al. / Tetrahedron Letters 46 (2005) 803–805
805
1
6
. Arzoumanian, H.; Jean, M.; Nuel, D.; Garcia, J. L.;
Rosas, N. Organometallics 1997, 16, 2726.
. Rosas, N.; Cabrera, A.; Sharma, P.; Arias, J. L.; Garcia, J.
L.; Arzoumanian, H. J. Mol. Catal. A: Chem. 2000, 156,
1720 (CO
0.87 (3H, t, CH
m, CH –CH –CH ); 2.69 (1H, dd, CH H ); 3.30 (1H, dd,
2
H); 1685. H NMR (300 MHz, CDCl
3
) ppm:
2
3 2 2
); 1.59 (2H, h, CH –CH –CH ); 2.39 (2H,
7
3
2
2
a
b
1
3
CH); 4.12 (1H, dd, CH
NMR (75 MHz, CDCl ) ppm: 13.6 CH
CH ; 44.6 CH –CH –CH ; 45.8 CH ; 46.1 CH; 127.6 C
127.8 C ; 128.8 C ; 137.5 C ; 177.7 CO H; 208.4 C@O.
H
a b
); 7.27 (5H, m, C
6
5
H ).
C
1
03.
3
3
; 17.1 CH
3
–CH –
2
8
9
. Rosas, N.; Salm o´ n, M.; Sharma, P.; Alvarez, C.; Ramirez,
R.; Garcia, J. L.; Arzoumanian, H. J. Chem. Soc., Perkin
Trans. 1 2000, 1493.
. Rosas, N.; Sharma, P.; Alvarez, C.; Cabrera, A.; Ram ´ı rez,
R.; Delgado, A.; Arzoumanian, H. J. Chem. Soc., Perkin
Trans. 1 2001, 19, 2341.
2
3
2
2
2
o
;
m
p
ip
2
12. Brown, H. C.; Khire, U. R.; Narla, G.; Rocherla, U. S. J.
Org. Chem. 1995, 60, 544.
13. Brandsma, L. Preparative Acetylenic Chemistry. Studies in
Organic Chemistry; Elsevier: New York, 1988.
14. X-ray data of 4-keto-2-phenylheptanoic acid 2g: empirical
1
0. Rosas, N.; Sharma, P.; Cabrera, A.; Penieres, G.; Garcia,
J. L.; Maldonado, L. A. Heterocycles 2003, 60, 2631.
1. Experimental procedure: all materials were obtained from
commercial suppliers and used without further purifica-
tion. 5-Hexyn-3-ol, 6-heptyn-4-ol and 1-phenylhex-1-yn-3-
14 3
formula = C13H O ; formula weight = 218.2; crystal sys-
tem = monoclinic; space group = P2 /n; a = 15.075(3) A;
˚
1
1
˚
˚
b = 5.5890(10) A; c = 15.595(3) A, b = 112.98(3)ꢁ; V =
˚
3
1209.7(6) A ; z = 4; density (calcd) = 1.198 Mg m
À3
;
1
2,13
À1
one were synthesized according to published methods.
A typical experiment was performed as follows: in a
round-bottom flask were mixed 1 mmol of K [Ni(CN) ],
0 mmol KCN and 10 mmol of NaBH , then 12.5 mL of
absorption coefficient = 0.085 mm ; crystal size = 0.17 ·
0.11 · 0.10 mm; 2h range = 7.0–45.0ꢁ; reflections collected
4473; independent reflections = 3519 (R int = 12.03%):
refinement method = full matrix least square on F ; R =
21.36%; Rw = 20.88%; Largest and mean D/r = 5.026,
0.243;
2
4
2
1
4
water was added yielding an orange solution that was
stirred and heated at 393 K. To this solution was then
added 10 mmol of a-alkynol 1a–f and the stirring contin-
ued at 393 K for 12 h. At the end of the reaction, ethyl
ether (2 · 20 mL) was used to eliminate the impurities. The
aqueous phase was acidified with diluted HCl at pH ꢀ 1
(
Caution! HCN is generated). Ethyl ether (2 · 20 mL) was
used to extract the product. Evaporation of the solvent
after drying over Na SO gave the lactone. Spectral data
for 2a–g: 2-methyl-4-butyrolactone (2a). IR (KBr) cm
2
4
À1
:
1
1
d, CH ); 1.82 (1H, m, CH); 2.45 (2H, m, CH ); 4.17 (2H,
767 (C@O). H NMR (300 MHz, CDCl
3
) ppm: 1.20 (3H,
3
2
1
m, CH –O). C NMR (75 MHz, CDCl ) ppm: 15.45 CH ;
3
2
3
3
3
Dimethyl-4-butyrolactone (2b). IR (KBr) cm : 1764
0.99 CH; 34.50 CH
2
; 66.73 C–O; 180. 79 C@O. 2,4-
À1
1
(
C@O). H NMR (300 MHz, CDCl ) ppm: 1.08 (3H, dd,
3
CH
2H, m, CH
CDCl ) ppm: 15.90 CH
3
); 1.23 (3H, dd, CH
3
–CH–O); 1.92 (1H, m, CH); 2.45
1
3
(
2
); 4.43 (1H, m, CH–O). C NMR (75 MHz,
O(1)–C(7) 1.336(22); C(3)–C(5) 1.515(24); O(4)–C(7)
1.253(29); C(6)–C(7) 1.477(37); C(9)–C(10) 1.491(23);
O(2)–C(5) 1.202(23); C(3)–C(6) 1.551(26); C(5)–C(9)
1.501(27); C(6)–C(8) 1.500(25); C(8)–C(12) 1.373(31);
C(10)–C(15) 1.474 (38); C(5)–C(3)–C(6) 110.6(15); O(2)–
C(5)–C(9) 122.2(17); C(3)–C(6)–C(7) 109.6(15); C(7)–
C(6)–C(8) 107.3(19); C(6)–C(8)–C(11) 122.1(16); O(2)–
C(5)–C(3) 121.1(18); C(3)–C(5)–C(9) 116.8(15); C(3)–
C(6)–C(8) 112.4(14); O(1)–C(7)–O(4) 117.5(24); O(4)–
C(7)–C(6) 127.6(17); O(6)–C(8)–C(12) 120.8(18). Crystal-
lographic data has been deposited with the Cambridge
Crystallographic Data Centre as supplementary Publica-
tion No. CCDC 256739.
3
3
; 21.23 CH
3
–CH–O; 34.13 CH;
3
9.28 CH ; 75.32 C–O; 180.48 C@O. 4-Ethyl-2-methyl-4-
2
À1
1
butyrolactone (2c). IR (KBr) cm : 1763 (C@O); H NMR
(
300 MHz, CDCl
3
) ppm: 0.98 (3H, dd, CH
–CH
3
–CH
2
); 1.09
(
3H, dd, CH ); 1.32 (2H, m, CH
3
3
2
); 1.93 (1H, m, CH);
1
3
2
.45 (2H, m, CH ); 4.47 (1H, m, CH–O). C NMR
2
(
75 MHz, CDCl
CH –CH ; 35.0 CH; 39.20 CH
C@O. 2-Methyl-4-propyl-4-butyrolactone (2d). IR (KBr)
3
) ppm: 11.30 CH
3
–CH
2 3
; 15.90 CH ; 22.30
3
2
2
; 74.11 CH–O; 180. 6
À1
1
cm : 1763 (C@O); H NMR (300 MHz, CDCl ) ppm: 1.0
3
(
3H, dd, CH
m, CH –CH
1H, m, CH); 2.41 (2H, m, CH ); 4.41 (1H, m, CH–O).
3
–CH
2
–CH
2
); 1.10 (3H, dd, CH
3
); 1.20 (2H,
3
2
–CH
2
); 1.31(2H, m, CH
3
–CH
2
–CH ); 1.90
2
1
3
(
C
15. Sharpe, A. G. The Chemistry of Cyano Complexes of the
Transition Metals; Academic: London, 1976.
16. Garcia, J. J.; Jones, W. D. Organometallics 2000, 19, 5544.
17. Garcia, J. J.; Brunkan, N. M.; Jones, W. D. J. Am. Chem.
Soc. 2002, 124, 9547.
2
NMR (75 MHz, CDCl
3
) ppm: 10.21 CH
3
; 16.01 CH ; 22.11 CH
3
–CH
–CH
2
–CH
2
2
;
;
1
3
3.20 CH
5.12 CH; 39.10 CH
3
–CH
2
–CH
2
3
2
–CH
2
; 73.27 CH–O; 180.7 C@O. 2-
À1
Hydroxymethyl-4-butyrolactone (2e). IR (KBr) cm : 1767
1
(
C@O); 3504 (OH). H NMR (300 MHz, CDCl
.88 (1H, qn, CH); 2.50 (2H, m, CH ); 4.15 (2H, m, CH
O); 4.20 (2H, m, CH –O); 7.85 (br, OH). C NMR
3
) ppm:
18. Brunkan, N. M.; Brestensky, D. M.; Jones, W. D. J. Am.
Chem. Soc. 2004, 126, 3627.
1
2
2
–
1
3
19. When the reaction was carried out with benzonitrile
according to experimental section (first extraction was
avoided) the IR spectrum of the product showed a mC–N at
2
(
75 MHz, CDCl ) ppm: 49.29 CH; 34.56 CH ; 66.82 CH –
3 2 2
O; 62.88 CH –OH; 182. 88 C@O. 2-Phenyl-4-propyl-4-
2
À1
1
À1
butyrolactone (2f). IR (KBr) cm : 1765 (C@O); H NMR
1739 cm . On the other hand, when the reaction is carried
(
300 MHz, CDCl ) ppm: 0.96 (3H, t, CH –CH –CH );
6 5 3 2
out according to experimental section, but [(C H ) P] NCl
3
3
2
2
1
CH
.26 (2H, m, CH
3
–CH
2
–CH
2
); 1.53 (2H, m, CH
); 4.29 (1H, m,
). C NMR (75 MHz, CDCl
ppm: 10.42 CH –CH –CH ; 13.34 CH –CH –CH ; 23.65
3
–CH
2
–
is added to the reaction medium before of the second
extraction, the IR spectrum of the product showed a mC–N
at 2112 cm . Both signals were similar to those ones
observed to the reversible oxidative addition of benzonit-
rile on Ni(0) (Ref. 15).
2
); 2.08 (1H, m, CH); 2.35 (2H, m, CH
2
1
3
À1
CH–O); 7.15 (7H, m, C
6
H
5
3
)
3
2
2
3
2
2
CH
C
3
–CH
2
–CH
; 127.4 C ; 128.3 C
2 2
; 36.45 CH; 40.10 CH ; 74.87 CH–O; 127.6
; 136.1 Cip 177.5 C@O. 4-Keto-2-
20. McKenzie, C. J.; Robson, R. J. Chem. Soc., Chem.
Commun. 1988, 112.
o
m
p
À1
phenylheptanoic acid (2g). IR (KBr) cm : 1709 (C@O);