Manganese-mediated carbon-carbon bond formation in aqueous media: Chemoselective allylation and pinacol coupling of aryl aldehydes

Article abstract of DOI:10.1021/jo980535z

The use of manganese as a mediator for allylations and pinacol couplings in aqueous media was investigated. The combination of manganese and copper is found to be a highly effective mediator for the allylation of aryl aldehydes in water. Such a combination is found to be more reactive than other previously reported metals in aqueous media. No reaction was observed with either manganese or copper alone as the mediator. Only a catalytic amount of copper is required for the proceeding of the reaction. The uses of Cu(0), Cu(I), and Cu(II) as the copper source are all effective. The use of a catalytic amount of manganese combined with a stoichoimetric amount of copper led to the failure of the reaction. Allyl chloride is found to be more effective than allyl bromide for the corresponding reaction. The use of substituted allyl halides gave a mixture of regio- and diastereoisomers. Aromatic aldehydes reacted chemoselectively in the presence of aliphatic aldehydes. An exclusive selectivity was also observed when both an aliphatic and an aromatic aldehyde functionalities are present in the same molecule. In the presence of acetic acid or ammonium chloride, manganese was found to effect the pinacol-coupling reaction in water. The reaction proceeds selectively with aryl aldehydes.

Full text of DOI:10.1021/jo980535z

7498
J . Org. Chem. 1998, 63, 7498-7504
Ma n ga n ese-Med ia ted Ca r bon -Ca r bon Bon d F or m a tion in Aqu eou s
Med ia : Ch em oselective Allyla tion a n d P in a col Cou p lin g of Ar yl
Ald eh yd es
Chao-J un Li,* Yue Meng, and Xiang-Hui Yi
Department of Chemistry, Tulane University, New Orleans, Louisiana 70118
J ihai Ma and Tak-Hang Chan*
Department of Chemistry, McGill University, Montreal, PQ, Canada H3A 2K6
Received March 23, 1998
The use of manganese as a mediator for allylations and pinacol couplings in aqueous media was
investigated. The combination of manganese and copper is found to be a highly effective mediator
for the allylation of aryl aldehydes in water. Such a combination is found to be more reactive than
other previously reported metals in aqueous media. No reaction was observed with either
manganese or copper alone as the mediator. Only a catalytic amount of copper is required for the
proceeding of the reaction. The uses of Cu(0), Cu(I), and Cu(II) as the copper source are all effective.
The use of a catalytic amount of manganese combined with a stoichoimetric amount of copper led
to the failure of the reaction. Allyl chloride is found to be more effective than allyl bromide for the
corresponding reaction. The use of substituted allyl halides gave a mixture of regio- and
diastereoisomers. Aromatic aldehydes reacted chemoselectively in the presence of aliphatic
aldehydes. An exclusive selectivity was also observed when both an aliphatic and an aromatic
aldehyde functionalities are present in the same molecule. In the presence of acetic acid or
ammonium chloride, manganese was found to effect the pinacol-coupling reaction in water. The
reaction proceeds selectively with aryl aldehydes.
In tr od u ction
by manganese in water in the presence of a catalytic
amount of copper shows exclusive selectivity toward
aromatic aldehydes. Manganese was found equally
selective in promoting pinacol-coupling reactions of aryl
aldehydes in the presence of acetic acid or ammonium
chloride. Here we report the detailed study on this
subject.
The pursuit of synthetic targets with increasing com-
plexity has resulted in the development of reactions
which emphasize chemo-, regio-, diastereo-, and enanti-
oselectivity. In the defining of strategies and reactions
to construct complex molecules, chemoselectivity is re-
quired.1 Metal-mediated carbonyl addition generally has
a low chemoselectivity among different carbonyls. To
effect such a selectivity, previous efforts have shown that
it is possible to alkylate an aldehyde in the presence of a
ketone with certain selectivity.2 Recently the exploration
of aqueous medium metal-mediated reactions3 has shown
the potential for unusual chemoselectivity. Under such
reaction conditions, aldehydes have been shown to be
allylated selectively in the presence of ketones by tin
reagents.4 A considerable challenge is to effect a high
chemoselectivity between different aldehydes. Recently
we reported a complete chemoselectivity related to metal-
mediated carbonyl addition between aromatic and ali-
phatic aldehydes.5 The allylation of aldehydes mediated
Resu lts a n d Discu ssion
The recent interest in aqueous medium metal-medi-
ated carbon-carbon bond formation led to the continuing
search for more reactive and selective metal mediators
for such reactions. Among the reactions, allylations6 of
carbonyl compounds are studied most extensively.7 Met-
als such as tin, zinc, and indium have been found effective
for such transformations. The searching for a more
reactive metal mediator could prove difficult, since met-
als, such as sodium and magnesium, tend to react with
water. Metals that rapidly form an oxide shell would not
be suitable for mediating carbonyl nucleophilic addition
either. When one looks at the reductive potentials of
various metals, as well as their reactivity toward water,
manganese stands out as a promising candidate. While
maganese has a much more negative reductive potential
(E° ) -1.18 eV), pure manganese is not attacked by
water. Previously, manganese and manganese-based
reagents have been used in a variety of organic trans-
(1) Trost, B. M. Science 1985, 227, 908.
(2) For early studies toward effecting the selectivity of carbonyl
addition between ketones and aldehydes, see: Reetz, M. T.; Wenderoth,
B. Tetrahedron Lett. 1982, 23, 5259. Okude, Y.; Hirano, S.; Hiyama,
T.; Nozaki, H. J . Am. Chem. Soc. 1977, 99, 3179. Naruta, Y.; Ushida,
S.; Maruyama, K. Chem. Lett. 1979, 919. The use of organomanganese
reagents was found to give a high selectivity, see: Cahiez, G.; Figadere,
B. Tetrahedron Lett. 1986, 26, 4445.
(3) For recent reviews, see: Li, C. J . Tetrahedron 1996, 52, 5643.
Chan, T. H.; Isaac, M. B. Pure Appl. Chem. 1996, 68, 919. Li, C. J .;
Chan, T. H. Organic Reactions in Aqueous Media; J ohn Wiley & Sons:
New York, 1997. Lubineau, A.; Auge, J .; Queneau, Y. Synthesis 1994,
741. Li, C. J . Chem. Rev. 1993, 93, 2023.
(5) For a preliminary communication of this work, see: Li, C. J .;
Meng, Y.; Yi, X. H.; Ma, J . H.; Chan, T. H. J . Org. Chem. 1997, 62,
8632. Yi, X. H.; Meng, Y.; Ma, J . H.; Chan, T. H.; Li, C. J . Presented
at the 215th ACS Meeting, Dallas, TX 1998 (ORGN 237).
(4) Yanagisawa, A.; Inoue, H.; Morodome, M.; Yamamoto, H. J . Am.
Chem. Soc. 1993, 115, 10356. Petrier, C.; Eihorn, J .; Luche, J . L.
Tetrahedron Lett. 1985, 26, 1449.
(6) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207-2293.
S0022-3263(98)00535-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/01/1998

Manganese-Mediated Carbon-Carbon Bond Formation
J . Org. Chem., Vol. 63, No. 21, 1998 7499
formations in organic solvents.8 Manganese is also an
abundant element which makes manganese-based syn-
theses practical.
Ta ble 1. Allyla tion of Ben za ld eh yd e Med ia ted by
Mn -Cu in Wa ter
mediator
(equiv)
catalyst
(equiv)
yield
(%)a
entry
allyl halide
At the starting point, we examined the allylation
reaction of various carbonyl compounds. In terms of the
relative reactivity, the reaction between allyl chloride and
an aldehyde can generally be used as a marker of relative
effectiveness for different methods. When benzaldehyde
was stirred with allyl chloride and manganese in water
overnight at room temperature, no apparent reaction was
observed. The addition of aqueous 1 N HCl or saturated
NH4Cl to activate the metal lead to complicated mixtures.
Additionally, several aqueous buffer solutions (NH4Cl-
NaOH, Na2HPO4, and NaH2PO4) were examined as the
reaction solvents and no significant improvement was
observed. A different approach was subsequently con-
sidered. The activation of zinc with copper through the
formation of a zinc-copper couple is a well-known
process.9 When benzaldehyde was stirred with 1 equiv
of allyl chloride and a mixture of manganese-copper in
water for 8 h at room temperature, 62% of the corre-
sponding allylation product was isolated. Because of the
low boiling point of allyl chloride, part of it was lost
during the reaction process. When 3 equiv of allyl
chloride and manganese mediator was used, the isolated
yield of the allylation product increased to 83%.
1
2
3
4
5
6
7
8
9
allyl chloride
allyl chloride
allyl chloride
allyl chloride
allyl chloride
allyl chloride
allyl chloride
allyl chloride
allyl chloride
allyl bromide
Mn (3)
Cu (3)
Mn (3)
Mn (3)
Mn (3)
Mn (3)
Cu (3)
Cu (3)
Cu (3)
Mn (3)
no
no
Cu (0.1)
0
0
83
(95)
(92)
(92)
(5)
0
Cu (3)
CuCl (0.1)
CuCl2 (0.1)
Mn (0.1)
MnCl2 (0.1)
Mn(OAc)3 (0.1)
Cu (0.1)
0
36
10
Isolated yields; yields estimated by 1H NMR in parentheses.
a
The uses of a catalytic amount of Cu(0), Cu(I), or Cu(II)
gave the same result. On the other hand, the use of a
stoichiometric amount of Cu combined with a catalytic
amount of Mn (3:0.1:3 allyl chloride/Mn/Cu) provided less
than 5% of the desired product. The use of a catalytic
amount of Mn(II) or Mn(III) in place of Mn metal
completely depressed the product formation. Different
allyl halides were also tested as the allyl moiety. Inter-
estingly, changing allyl chloride to the usually more
reactive allyl bromide decreased the yield of the allylation
product (36%) under the same reaction conditions. In
addition, considerable amounts of byproducts (e.g., reduc-
tion and pinacol coupling) were observed when allyl
bromide was used instead of allyl chloride. Such a
seemingly abnormal behavior is most likely due to a
competing Wurtz-type coupling of the allyl bromide,
which was confirmed recently during a separate study
by one of us.10 Allyl chloride appeared less effective for
the Wurtz-coupling, which provided better a yield of
allylation. Throughout the reaction process, no apparent
change of pH value (6-7) of the media was observed.
Subsequently, a variety of aldehydes were tested with
this allylation method (eq 1), and the results are listed
in Table 2.
Thereupon, various combinations of manganese and
copper were examined to determine the roles that they
played in the reaction process (Table 1). The combined
use of manganese and copper appears critical. It inter-
esting to note that no reaction was observed with either
manganese or copper alone as the metal mediator. Only
a catalytic amount of copper is required for the reaction.
(7) For examples with various metal-mediators, see the following.
Sn: Nokami, J .; Wakabayashi, S.; Okawara, R. Chem. Lett. 1984, 869.
Uneyama, K.; Matsuda, H.; Torii, S. Tetrahedron Lett. 1984, 25, 6017.
Zn: Petrier, C.; Luche, J . L. J . Org. Chem. 1985, 50, 910. Einhorn, C.;
Luche, J . L. J . Organomet. Chem. 1987, 322, 177. Mattes, H.; Benezra,
C. Tetrahedron Lett. 1985, 26, 5697. Wilson, S. R.; Guazzaroni, M. E.
J . Org. Chem. 1989, 54, 3087. In: Li, C. J .; Chan, T. H. Tetrahedron
Lett. 1991, 32, 7017. Chan, T. H.; Li, C. J . J . Chem. Soc., Chem.
Commun. 1992, 747. Araki, S.; J in, S. J .; Idou, Y.; Butsugan, Y. Bull.
Chem. Soc. J pn. 1992, 65, 1736. Kim, E.; Gordon, D. M.; Schmid, W.;
Whitesides, G. M. J . Org. Chem. 1993, 58, 5500. Paquette, L.; Mitzel,
T. M. J . Am. Chem. Soc. 1996, 118, 1931. Li, C. J .; Chen, D. L.; Lu, Y.
Q.; Haberman, J . X.; Mague, J . T. J . Am. Chem. Soc. 1996, 118, 4216.
Wang, R.; Lim, C. M.; Tan, C. H.; Lim, B. K.; Sim, K. Y.; Loh, T. P.
Tetrahedron: Asymmetry 1995, 6, 1825. Bi: Wada, M.; Ohki, H.; Akiba,
K. Y. Bull. Chem. Soc. J pn. 1990, 63, 1738; J . Chem. Soc., Chem.
Commun. 1987, 708. Katritzky, A. R.; Shobana, N.; Harris, P. A.
Organometallics 1992, 11, 1381. Minato, M.; Tsuji, J . Chem. Lett. 1988,
2049. Ge: Akiyama, T.; Iwai, J . Tetrahedron Lett. 1997, 38, 853. For
manganese-mediated allylations in organic solvent, see: Hiyama, T.;
Obayashi, M.; Nakamura, A. Organometallics 1982, 1, 1249. Cahiez,
G.; Chavant, P. Y. Tetrahedron Lett. 1989, 30, 7373 and the patents
cited therein (the addition of a small amount of a metal salt, e.g., ZnCl2,
CdCl2, and HgCl2, enhanced the reactivity of manganese in aprotic
solvent).
(8) For other recent studies on manganese mediated reactions, see:
Cahiez, C.; Laboue, B. Tetrahedron Lett. 1989, 30, 7369. Cahiez, C.;
Laboue, B. Tetrahedron Lett. 1989, 30, 7369. Cahiez, G.; Alami, M.
Tetrahedron Lett. 1989, 30, 7373; 1990, 31, 7423. Furstner, A.;
Brunner, H. Tetrahedron Lett. 1996, 37, 7009. Takai, K.; Ueda, T.;
Ikeda, N.; Moriwake, T. J . Org. Chem. 1996, 61, 7990-7991. Takai,
K.; Ueda, T.; Hayashi, T.; Moriwake, T. Tetrahedron Lett. 1996, 37,
7049-7052. Coulton, S.; Hanlon, P. J .; Rogers, N. H. J . Chem. Soc.,
Perkin 1 1982, 729. Friour, G.; Cahiez, G.; Normant, F. J . Synthesis
1985, 50. Furstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 12349.
Tang, J .; Yorimitsu, H.; Oshima, K. Tetrahedron Lett. 1997, 38, 9019.
Kakiya, H.; Inoue, R.; Oshima, K. Tetrahedron Lett. 1997, 38, 3275.
Vaughan, W. S.; Gu, H. H.; McDaniel, K. F. Tetrahedron Lett. 1997,
38, 1885. Inoue, R.; Shinokubo, H.; Koichiro, O. J . Org. Chem. 1998,
63, 910. Takai, K.; Kaihara, H.; Ikeda, N. J . Org. Chem. 1997, 62, 8612.
Hojo, M.; Aihara, H.; Akira, H. J . Org. Chem. 1997, 62, 8610. Takai,
K.; Ueda, T.; Moriwake, T. J . Org. Chem. 1997, 62, 8728.
It was found that various aromatic aldehydes were
allylated efficiently by allyl chloride and manganese in
water. It is noteworthy to mention that aromatic alde-
hydes bearing various halogens were allylated without
any problem (entries 5-7 and 13-15). The allylations
of a hydroxylated aldehyde and a cyano-substituted
aldehyde, as well as cinnamaldehyde, were equally
successful (entries 8, 16, and 12). On the other hand,
aliphatic aldehydes are inert under the reaction condi-
tions (entry 11).11 The result could be attributed to the
difference in reductive potentials between aliphatic and
aromatic aldehydes. Such an unusual reactivity differ-
ence between an aromatic aldehyde and an aliphatic
aldehyde suggests the possibility of a useful chemoselec-
tivity.
(10) Ma, J .; Chan, T. H. Tetrahedron Lett. 1998, 39, 2499. For a
related Wurtz-type reaction in organic solvent, see: Kasatkin, A. N.;
Tsypyshev, O. Y.; Romanova, T. Y.; Tolstikov, G. A. Organomet. Chem.
USSR 1989, 1, 830.
(11) A related selectivity was recently observed in the allylation of
carbonyl compounds with an allylmanganese reagent in organic
solvent; see: Cahiez, G. An. Quim. 1995, 91, 561.
(9) Smith, R. D.; Simmons, H. E. Org. Synth. 1961, 41, 72.

7500 J . Org. Chem., Vol. 63, No. 21, 1998
Ta ble 2. Allyla tion of Ald eh yd es Med ia ted Mn -Cu
Li et al.
performed with allylmagnesium bromide12 in ether.
Rather than accelerating the reaction, the addition of a
water-soluble quaternary ammonium salt (tetraethylam-
monium chloride, 0.1 equiv) depressed the reaction.
An intramolecular discrimination study has also been
carried out on a compound bearing both aromatic and
aliphatic carbonyl groups. Reaction of 4-(chloromethyl)-
stilbene (4) with 4-pentenol (5) and sodium hydride in
DMF in the presence of a catalytic amount of 18-crown-6
generated, after ozonolysis of the intermediate, the
dialdehyde 6 (eq 3). Allylation of this dialdehyde under
Ta ble 3. Allyla tion of Ben za ld eh yd e by Va r iou s
Meth od s
yield
3a :3k a (%)b
entry
method
1
2
3
4
5
allyl chloride/Mn/Cu (1:3:0.1), H2O
allyl bromide/Zn (1:2), 0.1 N HCl(aq)
allyl bromide/In (1:1.2), 0.1 N HCl(aq)
allyl bromide/Sn (1:2), 0.1 N HCl(aq)
100:0
50:50
50:50
50:50
58
67
59
71
96
allylmagnesium bromide (2 equiv), Et2O 50:50
a
b
Ratios were determined by 1H NMR. Total isolated yields
without being optimized.
To test this hypothesis, competitive studies were
carried out between aliphatic and aromatic aldehydes
with different methods (eq 2) (Table 3). By using the
the standard conditions mediated by manganese and
copper resulted in 45% of the allylation product 7 (eq 4).
A complete chemoselectivity was observed in which the
allylation occurs exclusively on the aromatic carbonyl.
However, under the identical reaction conditions, no
present combination, a single allylation product was
generated when a mixture of heptaldehyde and benzal-
dehyde was reacted with allyl chloride. Such a selectivity
appears unique; aqueous methodologies mediated by
other metals (Zn, Sn, In) all generated a 1:1 mixture of
allylation products of both aldehydes. A 1:1 mixture of
products was also generated when the allylation was
(12) Wakefield, B. J . Organomagnesium Methods in Organic Chem-
istry; Academic Press: New York, 1995.

Manganese-Mediated Carbon-Carbon Bond Formation
J . Org. Chem., Vol. 63, No. 21, 1998 7501
Ta ble 4. P in a col Cou p lin g Med ia ted by Ma n ga n ese/
HOAc in Aqu eou s Med iu m
reaction was observed in compound 8 which involves a
long aliphatic chain. The addition of a cosolvent such
as THF did not improve the reaction. It is not clear what
inhibits the proceeding of the reaction. The uses of
terminally substituted allyl halides, e.g. 1-chloro-2-
butene, 3-methyl-1-chloro-2-butene, cinnamyl chloride,
and ethyl 4-bromocrotonate, for the reaction were all
successful yet generating mixtures of regio- and diaste-
reoisomers, which somewhat limits the present method.
The encouraging results obtained from the allylation
reaction led us to investigate other carbon-carbon bond
formations mediated by manganese under aqueous con-
ditions. The pinacol-coupling reaction is another funda-
mental reaction in organic chemistry.13 Traditionally,
pinacol coupling was effected by using active metals such
as sodium,14 lithium,15 or magnesium16 under anhydrous
conditions. Other reagents used for such a reaction
include the Zn-Cu couple,17 chromium or vanadium,18
SmI2,19 Ce-I2,20 Yb,21 and Bu3SnH,22 as well as TiCl3-
based reducing agents (the McMurry pinacol coupling).23
Recently, Clerici and Porta extensively studied the aque-
ous pinacol coupling reactions mediated by Ti(III).24
Aromatic ketones and aldehydes were coupled by TiCl3
in aqueous solution under alkaline or acetic condi-
tions.25,26 Very recently, Schwartz reported a diastereo-
selective pinacol coupling with a stereically hindered
(cyclopentadiene)titanium complex.27 Other metals such
as Zn-Cu have been also found to promote this reaction
under ultrasonic radiation in aqueous acetone.28 When
(13) For a recent review on pinacol coupling, see: Wirth, T. Angew.
Chem., Int. Ed. Engl. 1996, 35, 61-63.
(14) Nelsen, S. F.; Kapp, D. C. J . Am. Chem. Soc. 1986, 108, 1265.
(15) Pradhan, S. K.; Thakker, K. R. Tetrahedron Lett. 1987, 28, 1813.
(16) Gomberg, M.; Bachmann, W. E. J . Am. Chem. Soc. 1927, 49,
236. Fu¨rstner, A.; Csuk, R.; Rohrer, C.; Weidmann, H. J . Chem. Soc.,
Perkin Trans. 1 1988, 1729.
(17) Griner, M. G. Ann. Chim. Phys. 1892, 26, 304.
(18) Conant, J . B.; Cutter, H. B. J . Am. Chem. Soc. 1926, 48, 1016.
(19) Namy, J . L.; Souppe, J .; Kagan, H. B. Tetrahedron Lett. 1983,
24, 765.
(20) Imamoto, T.; Kusumoto, T.; Hatanaka, Y.; Yokoyama, M.
Tetrahedron Lett. 1982, 23, 1353.
benzaldehyde was reacted with manganese in the pres-
ence of a catalytic amount of acetic acid in water, the
corresponding pinacol-coupling product was obtained
smoothly. Other aryl aldehydes (eq 5) were coupled
(21) Hou, Z.; Takamine, K.; Fujiwara, Y.; Taniguchi, H. Chem. Lett.
1987, 2061.
(22) Hays, D. S.; Fu, G. C. J . Am. Chem. Soc. 1995, 117, 7283.
(23) For reviews, see: Fu¨rstner, A.; Bogdanovic´, B. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2443. McMurry, J . E. Chem. Rev. 1989, 89,
1513. Kahn, B. E.; Rieke, R. D. Chem. Rev. 1988, 88, 733.
(24) Clerici, A.; Porta, O. Tetrahedron Lett. 1982, 23, 3517.
(25) Clerici, A.; Porta, O. J . Org. Chem. 1982, 47, 2852. Gansauer,
A. Chem. Commun. 1997, 457-458.
(26) Clerici, A.; Porta, O.; Riva, M. Tetrahedron Lett. 1981, 22, 1043
and references cited therein. Very recently, activated manganese was
used for pinacol coupling; see; Rieke, R. D.; Kim, S. H. J . Org. Chem.
1998, 63, 5235.
(27) Barden, M. C.; Schwartz, J . J . Am. Chem. Soc. 1996, 118, 5484.
(28) Delair, P.; Luche, J . L. J . Chem. Soc., Chem. Commun. 1989,
398.
similarly to give the corresponding diols 9 (Table 4). On
the other hand, aryl and aliphatic ketones appeared to
be inert under the same reaction conditions and only the
reduced product was obtained with aliphatic aldehydes.
The pinacol coupling was found equally successful with

7502 J . Org. Chem., Vol. 63, No. 21, 1998
Li et al.
Ta ble 5. P in a col Cou p lin g of Ald eh yd es Med ia ted by
Mn in Aqu eou s NH4Cl
manganese powder in aqueous ammonium chloride solu-
tion, instead of using a catalytic amount of acetic acid.
Similarly, only aromatic aldehydes react under these
conditions (Table 5). However, only reduction was ob-
served when benzaldehyde was substituted by either a
cyano or a dimethylamino group (entries 6 and 7). An
intramolecular pinacol coupling occurred as well as the
intermolecular reaction (eq 6). Interestingly, only one
diastereomer (trans) was observed in this reaction. The
assignment of the stereochemistry was based on the
literature method.29
In conclusion, we found manganese to be highly effec-
tive for mediating both aqueous medium carbonyl allyl-
ations in the prescence of a catalytic amount of copper
reagent and pinacol-coupling reactions when combined
with either a catalytic amount of acetic acid or in aqueous
NH4Cl. In aqueous media, this metal offers a higher
reactivity (compared with previously reported ones) and
a complete chemoselectivity toward aromatic aldehydes
in allylation of carbonyl compounds and in pinacol
coupling. We are presently exploring this new reactivity
and selectivity in synthetic applications.
Exp er im en ta l Section
Air-sensitive reactions were generally conducted under a
positive pressure of dry N2 within glassware which had been
flame-dried under a stream of dry N2. Anhydrous solvents and
reaction mixtures were transferred by oven-dried syringe or
cannula. Manganese (325 mesh) and copper (200 mesh)
powders were purchased from Aldrich and were used directly
as received. Flash chromatography employed E. Merck silica
gel (Kiesegel 60, 230-400 mesh) purchased from Scientific
Adsorbents. Mass spectra and elemental analysis were ob-
tained at the Center of Instrumental Facility of Tulane
University and at the Biomedical Mass Spectrometry Unit of
McGill University. Water was deionized before use.
Gen er a l P r oced u r e for Allyla tion of th e Ald eh yd e. To
a 25 mL flask was added benzaldehyde (106 mg, 1 mmol), allyl
chloride (230 mg, 3 mmol), and water (2 mL). Then manga-
nese (165 mg, 3 mmol) and copper (6.4 mg, 0.1 mmol)
(premixed) were added to the reaction mixture. The flask was
stoppered and stirred vigorously at room temperature for 8 h
followed by quenching with 1 N HCl and extracted with diethyl
ether. The ethereal solution was washed with brine, dried over
anhydrous magnesium sulfate, and concentrated in vacuo. The
crude product was purified through flash column chromatog-
raphy on silica gel (hexanes-ethyl acetate) to give the desired
product (123 mg, 83%).
126, 118.4, 73.1, 65, 43.8. HRMS: calcd for C11H14O2 (M+),
m/e 178.0994; found, m/e 178.0995.
1-(2,6-Dich lor op h en yl)-3-bu ten -1-ol (3f). The reaction
of 2,6-dichlorobenzaldehyde (175 mg, 1 mmol) with allyl
chloride (230 mg, 3 mmol), manganese (165 mg, 3 mmol), and
copper (6.4 mg, 0.1 mmol) by the general allylation procedure
followed by column chromatography on silica gel (eluent: 10:1
hexane/ethyl acetate) generated 1-(2,6-dichlorophenyl)-3-buten-
1-ol (148 mg, 68% yield). IR (CDCl3): 3587, 3401, 1641, 1590,
1-(4-(Hyd r oxym eth yl)p h en yl)-3-bu ten -1-ol (3h ). The
reaction of 4-(hydroxylmethyl)benzaldehyde (136 mg, 1 mmol)
with allyl chloride (230 mg, 3 mmol), manganese (165 mg, 3
mmol), and copper (6.4 mg, 0.1 mmol) by the general allylation
procedure followed by column chromatography on silica gel
(eluent: 2:1 hexane/ethyl acetate) generated 1-(4-(hydroxy-
methyl)phenyl)-3-buten-1-ol (117 mg, 66% yield). IR
(CDCl3): 1695, 1641, 1421, 1209, 1041, 1010, 918, 821, 551
1573, 1446, 1184, 1099, 1015, 930, 778 cm-1
.
1H NMR (400
MHz, CDCl3, ppm): δ 7.28 (d, J ) 8.2 Hz, 2H), 7.13 (t, J ) 8.2
Hz, 1H), 5.76-5.89 (m, 1H), 5.48 (t, J ) 3.9 Hz, 1H), 5.04-
5.18 (m, 2H), 2.95 (br, 1H), 2.79-2.89 (m, 1H), 2.62-2.72 (m,
1H). 13C NMR (100 MHz, CDCl3, ppm): δ 137.2, 134.2, 133.8,
129.4, 128.9, 118.1, 71.4, 40.0. Anal. Calcd for C10H10Cl2O2:
C, 55.33; H, 4.64. Found: C, 55.21; H, 4.70.
cm-1 1H NMR (400 MHz, CDCl3, ppm): δ 7.33 (s, 4H), 5.73-
.
5.85 (m, 1H), 5.10-5.18 (m, 2H), 4.72 (t, J ) 8.4 Hz, 1H), 4.64
(s, 2H), 2.44-2.54 (m, 2H), 2.22 (br, 1H), 1.97 (br, 1H). 13C
NMR (100 MHz, CDCl3, ppm): δ 143.3, 140.2, 134.3, 127.1,
1-(3-F lu or op h en yl)-3-bu ten -1-ol (3o). IR (film): 3365,
1610, 1585, 1235 cm-1 1H NMR (400 MHz, CDCl3, ppm): δ
.
7.29 (m, 1H), 7.08 (m, 2H), 6.95 (m, 1H), 5.78 (m, 1H), 5.16
(m, 2H), 4.72 (t, J ) 7 Hz, 1H), 2.48 (m, 2H), 2.12 (br, 1H). 13
NMR (100 MHz, CDCl3, ppm): δ 164.15, 161.71, 146.51,
C
(29) J erina, D. M.; Selander, H.; Yagi, H.; Wells, M. C.; Davey, J .
F.; Mahadevan, V.; Gibson, D. T. J . Org. Chem. 1976, 41, 5988.

Manganese-Mediated Carbon-Carbon Bond Formation
J . Org. Chem., Vol. 63, No. 21, 1998 7503
129.85, 121.38, 118.91, 114.32, 112.63, 72.54, 43.80. Anal.
Calcd for C10H11FO: C,72.27; H, 6.67. Found: C,72.53; H,
6.09.
acetate) to give the title compound (140 mg, yield 78%). IR
(CDCl3): 1725, 1685, 1110 cm-1 1H NMR (400 MHz, CDCl3,
.
ppm): δ 10.01 (s, 1H), 9.78 (s, 1H), 7.86 (d, J ) 8 Hz, 2H),
7.51 (d, J ) 8 Hz, 2H), 4.55 (s, 2H), 3.50 (t, J ) 7.3 Hz, 2H),
2.48 (t, J ) 7.3 Hz, 2H), 1.40-1.80 (m, 12H). 13C NMR (100
MHz, CDCl3, ppm): δ 195.1, 191.1, 164.9, 139.5, 130.5, 130.4,
129.6, 69.4, 44.8, 29.3, 29.1, 29.0, 28.6, 25.9, 22.2. Anal. Calcd
for C17H24O3: C, 73.88; H, 8.75. Found: C, 71.77; H, 8.31.
P r ep a r a tion of 4-(4-Oxo-1-bu ta n oxy)m eth ylben za ld e-
h yd e (6). To a suspension of sodium hydride (120 mg, 60%
in mineral oil, 3 mmol) in DMF (80 mL) was added 4-penten-
1-ol (250 mg, 2.9 mmol). The mixture was stirred at room
temperature for 30 min under nitrogen followed by the
addition of 4-(chloromethyl)stilbene (448 mg, 2 mmol), and the
stirring was continued overnight. The reaction was quenched
with saturated aqueous ammonium chloride and extracted
with ether. The organic phase was washed with water and
brine, dried over magnesium sulfate, and concentrated. The
product (4-penten-1-yl 4-vinylbenzyl ether) was obtained by
column chromatography on silica gel (eluent: 10:1 hexane/
ethyl acetate). Polymerization of this compound was observed
within days on standing at room temperature. IR (CDCl3):
1641, 1629, 1570, 1512, 1448, 1406, 1361, 1103, 989, 908, 825,
Gen er a l P r oced u r e for P in a col Cou p lin g Rea ction by
Ma n ga n ese-Acetic Acid . 1,2-Dichlorobenzaldehyde (175
mg, 1 mmol) and manganese (138 mg, 2.5 mmol) were mixed
with water (3 mL), and then acetic acid (6 µL, 0.1 mmol) was
added. The reaction was left at room temperature for 16 h.
The reaction mixture was neutralized by adding hydrochloric
acid (1 M, 10 mL) and was extracted with ether (10 mL × 2).
The combined ether layer was washed twice with water (10
mL) and dried over anhydrous MgSO4. The solvent was
removed, and the residue was purified by a flash column (on
silica gel with ethyl acetate in hexane (10%) to give the diol
(150 mg, 0.43 mmol, 85%) as a mixture of threo and erythro
isomers (48:52). The ratio of threo and erythro isomers was
551 cm-1
.
1H NMR (400 MHz, CDCl3, ppm): δ 7.42 (d, J )
8.5 Hz, 2H), 7.32 (d, J ) 8.6 Hz, 2H), 6.66-6.75 (m, 1H), 5.78-
5.89 (m, 1H), 5.77 (d, J ) 18 Hz, 1H), 5.25 (d, J ) 12 Hz, 1H),
4.91-5.08 (m, 2H), 4.51 (s, 2H), 3.49 (t, J ) 7.2 Hz, 2H), 2.12-
2.22 (m, 2H), 1.68-1.78 (m, 2H). 13C NMR (100 MHz, CDCl3,
ppm): δ 138.3, 138.2, 136.9, 136.6, 127.9, 126.2, 114.8, 113.7,
72.6, 69.7, 30.4, 29.0.
1
measured by H NMR.30
Gen er a l P r oced u r e for P in a col Cou p lin g Rea ction by
Ma n ga n ese-Am m on iu m Ch lor id e. To a mixture of ben-
zaldehyde (106 mg, 1 mmol) in 3 mL of H2O-THF (4:1) at room
temperature was added ammonium chloride (161 mg, 3 mmol)
and manganese powder (165 mg, 3 mmol) in one portion. The
reaction mixture was stoppered and stirred vigorously at room
temperature for 16 h. The reaction was then stopped by the
addition of 1 N HCl. The mixture was extracted with ether.
The combined organic phase was washed with brine, dried over
magnesium sulfate, and concentrated. The corresponding
allylation product, as a mixture of threo and erythro isomers
(39:61) (70 mg, yield 65%), was isolated by flash column
chromatography on silica gel eluting with hexane/ethyl acetate
(10:1).
The above compound (910 mg, 3.3 mmol) was dissolved in
methylene chloride (20 mL). The solution was ozonized at -78
°C until the appearance of a bluish color solution. Dimethyl
sulfide (500 mg, 8.1 mmol) was added, and the mixture was
allowed to warmed to room temperature slowly. The stirring
was continued for another 2 h. The solvent was removed in
vacuo, and the crude material was subjected to column
chromatography on silica gel (eluent: 2:1 hexane/ethyl acetate)
to give the title compound (556 mg, yield 82%). IR (CDCl3):
2741, 1726, 1607, 1582, 1396, 1362, 1311, 1209, 1176, 1184
cm-1 1H NMR (400 MHz, CDCl3, ppm): δ 9.98 (s, 1H), 9.78
.
(s, 1H), 7.85 (d, J ) 8 Hz, 2H), 7.47 (d, J ) 8 Hz, 2H), 4.55 (s,
2H), 3.53 (t, J ) 7.3 Hz, 2H), 2.58 (t, J ) 7.3 Hz, 2H), 1.93-
2.02 (m, 2H). 13C NMR (100 MHz, CDCl3, ppm): δ 202.2, 192,
145.4, 135.7, 129.9, 127.6, 72.2, 69.7, 40.9, 22.5. HRMS: calcd
for C12H15O3 (M + H+), m/e 207.1021; found, m/e 207.1021.
4-(4′-(3-bu ten -1-ol-1-yl)ben zoxy)bu tyr aldeh yde (7). The
reaction of 4-((4-oxo-1-butanoxyl)methyl)benzaldehyde (103
mg, 0.5 mmol) with allyl chloride (116 mg, 1.5 mmol),
manganese (82.5 mg, 1.5 mmol), and copper (3.2 mg, 0.05
mmol) by the general allylation procedure followed by column
chromatography on silica gel (eluent: 5:1 hexane/ethyl acetate)
generated 4-(4′-(3-buten-1-ol-1-yl)benzoxyl)butyraldehyde (56
mg, 45% yield). IR (CDCl3): 2800, 1722, 1641, 1417, 1359,
1,2-Bis(2,3-d ich lor op h en yl)-1,2-et h a n ed iol (9f). The
compound is prepared from 2,3-dichlorobenzaldehyde by the
above general pinacol coupling procedure. IR (CDCl3): 1035,
1058, 1216, 3153 cm-1 1H NMR (400 MHz, CDCl3, ppm): δ
.
1.70 (s, 1H), 5.36 (s, 1H), 2.85 (s, 1H), 5.64 (s, 1H), 7.05-7.70
(m, 3H). 13C NMR (100 MHz, CDCl3, ppm): δ 72.30, 72.97,
126.25, 126.59, 126.70, 129.12, 129.41, 130.65, 130.79, 131.76,
132.47, 137.77, 138.94. HRMS: calcd for C14H9Cl4O (M + H+
- H2O), m/e 332.9407; found, m/e 332.9406.
1,2-Bis(p-(tr iflu or om eth yl)p h en yl)-1,2-eth a n ed iol (9g).
The compound is prepared from p-(trifluoromethyl)benzalde-
hyde by the general pinacol coupling procedure. IR (CDCl3):
1041, 1215, 3154 cm-1 1H NMR (400 MHz, CDCl3, ppm): δ
.
1097, 916, 823, 540 cm-1 1H NMR (400 MHz, CDCl3, ppm):
.
2.45 (s, 1H), 4.96 (s, 1H), 7.45-7.65 (m, 4H); 2.98 (s, 1H), 4.99
(s, 1H), 7.45-7.65 (m, 4H). 13C NMR (100 MHz, CDCl3,
ppm): δ 72.30, 72.97, 126.25, 126.59, 126.70, 129.12, 129.41,
130.65, 130.79, 131.76, 77.16, 78.35, 124.58, 126.66, 126.71,
129.46, 130.10, 142.37, 142.53. HRMS: calcd for C16H11F6O
(M + H+ - H2O), m/e 333.0714; found, m/e 332.0713.
δ 9.77 (t, J ) 1.2 Hz, 1H), 7.35-7.25 (m, 4H), 5.81-5.72 (m,
1H), 5.21-5.08 (m, 2H), 4.75-4.70 (m, 1H), 4.47 (s, 2H), 3.50
(t, J ) 6 Hz, 2H), 2.61-2.41 (m, 4H), 1.98-1.89 (m, 2H), 1.72
(br, 1H). 13C NMR (100 MHz, CDCl3, ppm): δ 202.4, 143.3,
137.5, 134.4, 127.8, 125.9, 118.5, 73, 72.7, 69.2, 43.9, 41, 22.5.
HRMS: calcd for C15H20O3 (M + H+ - H2O), m/e 231.1385;
found, m/e 231.1386.
Ack n ow led gm en t. The research was supported by
the NSF-EPA joint program for a Sustainable Environ-
ment and the Center for Photoinduced Processes (NSF/
LEQSF). Acknowledgment is also made to the donors
of the Petroleum Research Fund (administered by the
ACS), the LEQSF, the NSF for a CAREER Award (to
C.J .L.), and the NSERC for partial support of this
research.
P r ep a r a tion of 4-((9-Oxo-1-n on a n oxy)m eth yl)ben za l-
d eh yd e (8). To a suspension of sodium hydride (62 mg, 60%
in mineral oil, 1.5 mmol) in DMF (10 mL) was added Z-octa-
decen-1-ol (322 mg, 1.2 mmol). The mixture was stirred at
room temperature for 15 min under nitrogen followed by the
addition of 4-(chloromethyl)stilbene (224 mg, 1 mmol), and the
stirring was continued for 4 h. The reaction was quenched
with saturated aqueous ammonium chloride and extracted
with ether. The organic phase was washed with water and
brine, dried over magnesium sulfate, and concentrated.
The above crude compound (300 mg, 0.65 mmol) was
dissolved in methylene chloride (10 mL). The solution was
ozonized at -78 °C until the appearance of a bluish color
solution. Dimethyl sulfide (200 mg, 3.3 mmol) was added, and
the mixture was warmed to room temperature slowly. The
stirring was continued for another 2 h. The solvent was
removed in vacuo, and the crude material was subjected to
column chromatography on silica gel (eluent: 2:1 hexane/ethyl
Registr y Nu m ber s (su p p lied by a u th or ): 1-phenyl-3-
buten-1-ol, 936-58-3; 1-(2-furanyl)-3-buten-1-ol, 6398-51-2;
1-(2-naphthyl)-3-buten-1-ol, 76635-86-4; 1-(4-chlorophenyl)-3-
buten-1-ol, 14506-33-3; 1-(4-methylphenyl)-3-buten-1-ol, 24165-
63-7; 1-(2-methylphenyl)-3-buten-1-ol, 24165-62-6; 1-(4-meth-
oxyphenyl)-3-buten-1-ol, 24165-60-4; 1-(3-methoxyphenyl)-3-
(30) Handa, Y.; Inanaga, J . Tetrahedron Lett. 1987, 28, 5717.

7504 J . Org. Chem., Vol. 63, No. 21, 1998
Li et al.
buten-1-ol, 156091-01-9; 1-(3-bromophenyl)-3-buten-1-ol, 114095-
73-7; 4-(hydroxymethyl)benzaldehyde, 52010-97-6; 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol, 4464-76-0; 1,2-bis(4-bromophen-
yl)-1,2-ethanediol, 126082-5-50-6; 1,2-diphenyl-1,2-ethanediol,
492-70-6; 1,2-bis(4-chlorophenyl)-1,2-ethanediol, 38152-44-2;
1,2-bis(3,4-dichlorophenyl)-1,2-ethanediol, 34848-44-7; 1,2-bis-
116204-40-1; 1,2-bis(1-naphthenyl)-1,2-ethanediol, 116204-39-
8; 1-phenyl-1,5-hexadien-3-ol, 13891-95-7; 4-fluoro-R-2-prope-
nylbenzenemethanol, 136185-86-9; 2-fluoro-R-2-propenylben-
zenemethanol, 144486-11-3; 4-(1-hydroxy-3-butenyl)benzonitrile,
71787-53-6; 1,1′-biphenyl-2,2′-dicarboaldehyde, 1210-05-5; 9,-
10-dihydro-9,10-phenanthrenediol, 25061-77-2.
(p-tolyl)-1,2-ethanediol,
24133-59-3;
1,2-bis(o-tolyl)-1,2-
ethanediol, 64158-25-4; 1,2-bis(p-phenylphenyl)-1,2-ethanediol,
J O980535Z