Acid-mediated, chromium-catalyzed allylation of aldehydes

Article abstract of DOI:10.1081/SCC-120004841

Allyl bromides are efficiently coupled with aryl and aliphatic aldehydes in the presence of manganese metal, collidine hydrochloride, bis(diisopropylphosphino)ethane and chromium dichloride. Homoallylic alcohols are isolated in good to excellent yields directly from the reaction mixture.

Full text of DOI:10.1081/SCC-120004841

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ACID-MEDIATED, CHROMIUM-CATALYZED ALLYLATION OF
ALDEHYDES
Kevin H. Shaughnessy a & Rongcai Huang a
a Department of Chemistry , The University of Alabama , Box 870336, Tuscaloosa, AL,
35487-0336, U.S.A.
Published online: 16 Aug 2006.
To cite this article: Kevin H. Shaughnessy & Rongcai Huang (2002) ACID-MEDIATED, CHROMIUM-CATALYZED ALLYLATION OF
ALDEHYDES, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
32:13, 1923-1928, DOI: 10.1081/SCC-120004841
To link to this article: http://dx.doi.org/10.1081/SCC-120004841
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SYNTHETIC COMMUNICATIONS, 32(13), 1923–1928 (2002)
ACID-MEDIATED,
CHROMIUM-CATALYZED ALLYLATION
OF ALDEHYDES
*
Kevin H. Shaughnessy andRongcai Huang
Department of Chemistry, The University of Alabama,
Box 870336, Tuscaloosa, AL 35487-0336, USA
ABSTRACT
Allyl bromides are efficiently coupled with aryl and aliphatic
aldehydes in the presence of manganese metal, collidine
hydrochloride, bis(diisopropylphosphino)ethane and chro-
mium dichloride. Homoallylic alcohols are isolated in good
to excellent yields directly from the reaction mixture.
Key Words: Chromium; Catalytic; Allylation; Acid-mediated
Chromium mediated addition of organichalides to aldehydes has
become an important synthetic methodology due to the high functional
group tolerance of organochromium species (Eq. 1).[1,2] A drawback of
the early work by Nozaki and Hiyama,[3] and later Kishi,[4] was the need
to use large excesses of chromium(II) salts (4–100 equivalents) to obtain the
desired products. The recent development of chromium-catalyzed Nozaki–
Hiyama–Kishi (NHK) reactions has greatly increased the utility of
this methodology.[5,6] While catalytic in chromium, these systems require a
*Corresponding author. E-mail: kshaughn@bama.ua.edu
1923
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1924
SHAUGHNESSY AND HUANG
stoichiometric amount of reductant and trimethylsilyl chloride (TMSCl),
neither of which can be easily recovered. These features limit the
large-scale application of this methodology. Therefore as part of our
interest in developing more efficient versions of this methodology, we
report the chromium-catalyzed allylation of aldehydes mediated by
collidine-hydrochloride.
ð1Þ
The role of TMSCl in the catalytic systems is to cleave the Cr–O bond
facilitating the reduction of the Cr(III) intermediate to the catalytically active
Cr(II) species.[2,7] Upon hydrolysis of the TMS-ether products of this reac-
tion, hexamethylsiloxane is produced, which cannot be readily recovered or
converted back to TMSCl. We reasoned that the use of an acid to cleave the
Cr–O bond would directly provide the desired alcohol product and the con-
jugate base of the acid, which could potentially be recycled. Gansauer[8] has
reported the use of pyridinium acids in titanium-catalyzed pinacolizations in
place of TMSCl to facilitate cleavage of titanium–alkoxide intermediates.
Since organochromium compounds react slowly with protic acids,[9] it
seemed likely that the coupling reaction could take place under acidic con-
ditions to directly give the desired alcohol products.
Collidine-hydrochloride, which had successfully been used by
Gansauer,[8] was tested initially in a series of small scale reactions using
manganese metal as reductant (Table 1).[5] Reactions mediated by
collidine-HCl proceeded slowly in the absence of ligands (Entry 1), but
occurred rapidly and in high yield in the presence of chelating diphosphines
(Entries 2–4). Both alkyl (R¼Me, i-Pr) and aryl (R¼Ph) diphosphines
ligands gave similar yields, although catalysts derived from 1,2-bis(diisopro-
pylphosphino)ethane (dippe) appeared to be more active. An N, N, N0, N0-
tetramethylethylenediamine (TMEDA) chromium(II) complex was no more
active than (THF)CrCl2. Both authentic[(dippe)CrCl ] and the complex
2 2
formed in situ from dippe and (THF)CrCl2 gave similar yields and activities
(Entries 2 and 7). As expected for this catalytic system, the active catalyst
could also be formed from an air stable chromium(III) salt—(THF)3CrCl3
(Entry 8), although CrCl3 formed a less active catalyst apparently due to its
low solubility. Replacement of collidine-HCl with pyridine-HCl or acetic
acid completely inhibited the reaction.
Collidine-HCl-mediated coupling reactions gave good to excellent
yields of homoallylicalochols for a range of allylicbromides with both

CHROMIUM-CATALYZED ALLYLATION OF ALDEHYDES
1925
Table 1. Ligands Effects in Collidine-HCl-Mediated Allylation of
Benzaldehydea
Time
(h)
Conversion
(%)b,c
Yield
(%)b
Entry
Ligand
1
2
3
4
5
6
7
8
9
THF
7
1
3
3
3
7
1
1
4.5
75
100
98
98
63
60
79
80
79
46
59
84
79
69
d
i-Pr2PCH2CH2Pi-Pr2
Ph2PCH2CH2PPh2
Me2PCH2CH2PMe2
t-Bu3P (2 eq/Cr)
TMEDAe
i-Pr2PCH2CH2Pi-Pr2
i-Pr2PCH2CH2Pi-Pr2
i-Pr2PCH2CH2Pi-Pr2
76
100
100
97
f
g
aReactions carried out using 0.2 mmol benzaldehyde, 0.4 mmol allyl-
bromide, 0.02 mmol (THF)CrCl2, the indicated ligand (0.02 mmol),
0.4 mmol. Mn, and 0.24 mmol collidine-HCl in THF at room tempera-
ture. bGC yields. cBenzaldehyde conversion. d0.01 mmol [(dippe)CrCl2]2.
f
g
e0.01 mmol [(TMEDA)CrCl2]2. CrCl3(THF)3. CrCl3.
aryl and alkyl aldehydes (Eq. 2, Table 2). Upon completion of the reaction,
GC analysis of the reaction mixture shows only the desired alcohol product
and collidine. The sterically demanding dippe ligand gave lower levels of
diastereoselectivity in the crotylation of benzaldehyde (3 : 1) than was
observed in the absence of ligand (>9 : 1).[5] Use of the less sterically
demanding ligands dmpe or dppe resulted in a 9 : 1 mixture of diastereomers
in similar yield to dippe as determined by GC analysis. Addition of geranyl
bromide to benzaldehyde or octyl aldehyde catalyzed by (dippe)CrCl2 gave
the homoallylic alcohol as a 9 : 1 ratio of diastereomers in excellent yield.
Allylation of electron-rich 4-methoxybenzaldehyde occurred in moderate
yield, but the reaction was unsuccessful with electron-poor 4-cyanobenzal-
dehyde due to competing pinacolization.
ð2Þ
In summary, in situ formed (dippe)CrCl2 efficiently catalyzes the ally-
lation of aldehydes in the presence of manganese powder and collidine-HCl.
The active catalyst can be conveniently formed from (THF)CrCl2, or

1926
SHAUGHNESSY AND HUANG
Table 2. Scope of the Collidine-HCl-Mediated Allylation of Aldehydes
Entry
RCHO
RBr
Product
Yielda d.r.b
86
1
PhCHO
Allyl bromide
2
PhCHO
PhCHO
Benzyl bromide
Prenyl bromide
72
97
3
4
PhCHO
PhCHO
Crotyl bromide
78
99
3 : 1
9 : 1
5
Geranyl bromide
6
7
n-C7H15CHO
n-C7H15CHO
Allyl bromide
94
96
Prenyl bromide
8
9
n-C7H15CHO
Geranyl bromide
98
64
9 : 1
4-MeOC6H5CHO Allyl bromide
aAverage isolated yield from 2 runs. Products characterized by 1H and
13C NMR, which were consistent with literature values.
bDiastereomericratio determined by GC and/or 1H NMR.
air-stable (THF)3CrCl3. A range of allylic bromides can be coupled with
both aryl and alkyl aldehydes in good to excellent yield. The alcohol product
can be isolated directly from the reaction mixture without the need for
deprotection. In principle, the collidine base could be recovered and recycled
to its conjugate acid.

CHROMIUM-CATALYZED ALLYLATION OF ALDEHYDES
EXPERIMENTAL
1927
General Procedure
In a drybox, a flask was charged with (THF)CrCl2 (0.2 mmol), dippe
(0.2 mmol), manganese powder (4 mmol), and collidine-HCl (2.2 mmol). The
flask was sealed with a septum and attached to a nitrogen line. THF (10 mL)
was added followed by the allyl bromide (4.0 mmol) and aldehyde
(2.0 mmol). Addition of the allyl bromide and aldehyde gave a deep sky
blue colored mixture, which faded to green upon completion of the reaction.
When TLC or GC analysis showed the aldehyde had been consumed, the
reaction mixture was quenched in 10% HCl and extracted with ether. The
crude material was purified by flash chromatography eluting with 5–10%
ethyl acetate in hexanes.
ACKNOWLEDGMENTS
This work was supported by The University of Alabama and an Aid to
Education Grant from the DuPont Corporation.
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Received in the USA June 23, 2001