Aldehyde allylation with allylboronates providing α-addition products

Article abstract of DOI:10.1039/b924527h

Zn(OH)₂-catalyzed allylation reactions of allylboronates with aldehydes proceeded smoothly in aqueous media; when α-substituted allylboronates were employed, the α-addition products were obtained exclusively, and syn-adducts were formed selecti

Full text of DOI:10.1039/b924527h

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Aldehyde allylation with allylboronates providing a-addition productsw
Shu¯ Kobayashi,* Toshimitsu Endo, Uwe Schneider and Masaharu Ueno
Received (in Cambridge, UK) 23rd November 2009, Accepted 4th January 2010
First published as an Advance Article on the web 18th January 2010
DOI: 10.1039/b924527h
Zn(OH)2-catalyzed allylation reactions of allylboronates
with aldehydes proceeded smoothly in aqueous media; when
a-substituted allylboronates were employed, the a-addition
products were obtained exclusively, and syn-adducts were
formed selectively in most cases; the use of Zn(OH)2 with dmp
(ligand) in aqueous media is the key to these reactions.
The reaction proceeded smoothly to afford the desired
homoallylic alcohol in high yield. However, since it was
difficult to distinguish catalyzed- and non-catalyzed reactions
at this stage, we then examined the reaction of a-methyl-
substituted allylboronate 2a with benzaldehyde (Table 1).
When the reaction was carried out in the absence of Zn(OH)2,
g-addition product 5a was obtained selectively (entry 1, non-
catalyzed reaction), while a mixture of a-adduct 4a and
g-adduct 5a (a/g = 45/55) was produced in the presence of
Zn(OH)2 (entry 2). It was noted that the very rare a-addition
product was formed in the presence of Zn(OH)2, although the
selectivities (both a/g and diastereoselectivity of 4a) were not
high. We further examined various parameters and finally
uncovered interesting ligand effects. When Zn(OH)2 was
combined with diamine 3a, the syn/anti ratio of 4a was
improved albeit with moderate a/g selectivity (entry 3). The
a/g selectivity was improved significantly in the presence of
Zn(OH)2 with 2,9-dimethyl-1,10-phenanthroline (3c, dmp),
and the syn/anti ratio was also high (entry 5). Furthermore,
when the reaction was conducted in dry CH3CN, g-adduct 5a
was obtained exclusively (entry 6). Thus, it was revealed that
the use of water is essential for the a-selectivity.9
Allylation is one of the most important and widely-used
carbon–carbon bond-forming reactions in organic chemistry.
While several allylating reagents have been extensively studied,
allylsilanes,1 allylstannanes2 and allylborons3–6 are among the
most popular species especially from a synthetic utility view-
point. As for the reactions with aldehydes, allylsilanes and
allylstannanes often react in the presence of Lewis acids via
acyclic transition states affording predominantly syn-products.1,2
Allylborons are more reactive than allylsilanes and allylstannanes.
They react with aldehydes spontaneously in the absence of a
catalyst via cyclic transition states due to the Lewis acidity of
boron, to give syn- and anti-products depending on the
geometry of starting allylborons.3–5 Lewis acid-catalyzed reac-
tions of allylboronates with aldehydes have also been
reported.6 While boron reagents have been established as
one of the most reactive and non-toxic reagents, g-addition
products have been obtained in almost all cases in the reactions
with aldehydes.7 We report here that a-addition products are
obtained exclusively by the reactions of allylboronates with
aldehydes in the presence of a catalytic amount of zinc
hydroxide [Zn(OH)2] with a ligand in aqueous media.
Several aldehydes were then treated with a-substituted
allylboronates in the presence of 5 mol% of Zn(OH)2–3c in
H2O–CH3CN (1/4) (Table 2). It is noted that in all cases only
a-adducts 4 were obtained in high yields. To the best of our
In an earlier report,8 we detailed that allylboronates reacted
with hydrazono esters in aqueous media in the presence of
zinc fluoride–chiral diamine complex to afford allylglycine
derivatives in high yields with high enantioselectivities. In that
work, a-addition products were obtained using a-substituted
allylboronates. We envisioned that the system might be
expanded to very rare, a-selective aldehyde allylation,
although the difference in reactivity between hydrazono esters
and aldehydes with allylboronates was critical; namely,
hydrazono esters do not react with allylboronates without cata-
lysts, while aldehydes react with allylboronates spontaneously
without catalysts as mentioned above.
Table 1 Effect of Zn(OH)2, ligands and water
Entry
Ligand (3)
Yield (%)
4a/5a
Syn/anti (4a)
1a
2
3
4
—
—
3a
3b
3c
3c
77
86
81
84
82
61
5/95
45/55
81/19
33/67
—
70/30
96/4
78/22
93/7
—
First, pinacol allylboronate was treated with benzaldehyde
in the presence of 10 mol% of Zn(OH)2 in H2O–CH3CN (1/4).
5
498/o2
6b
o2/498
a
b
In the absence of Zn(OH)2. In dry CH3CN.
Department of Chemistry, School of Science and Graduate School of
Pharmaceutical Sciences, The University of Tokyo,
The HFRE Division, ERATO,
Japan and Science Technology Agency (JST), Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan.
E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp; Fax: +81-3-5684-0634
w Electronic supplementary information (ESI) available: Experimental
section and spectroscopic data. See DOI: 10.1039/b924527h
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Table 2 Zn(OH)2–3c-catalyzed allylation reactions in aqueous media
Entry
R (aldehyde)
2 (R0)
Yield (%)
4/5
Syn/anti (4)
1
2
3
4
5
6
7
8
1a: R1 = H, R2 = H
2a (Me)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b (Et)
2c (Bu)
2d (i-Bu)
83
85
82
91
92
92
91
85
84
85
84
89
81
85
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
498/o2
94/6
93/7
93/7
96/4
94/6
91/9
97/3
93/7
86/14
77/23
50/50
89/11
88/12
90/10
1b: R1 = CH3, R2 = H
1c: R1 = OCH3, R2 = H
1d: R1 = NO2, R2 = H
1e: R1 = Br, R2 = H
1f: R1 = H, R2 = OCH3
1-Naphthaldehyde (1g)
4-Pyridinecarboxaldehyde (1h)
2-Thienylcarboxaldehyde (1i)
5-Methyl-2-furaldehyde (1j)
3-Phenylpropionaldehyde (1k)
9
10
11
12
13
14
1a
1a
1a
knowledge, during a relatively long history of allylboron
chemistry, this is a very rare case where a-addition products
are obtained exclusively from aldehydes.7,10 As for the syn/anti
selectivities of 4, high syn-selectivities were obtained in the
reactions of 2a with aromatic aldehydes (entries 1–7). While
the syn/anti selectivities decreased slightly for heteroaromatic
aldehydes (entries 8–10), a mixture of syn- and anti-4 was
obtained from 3-phenylpropionaldehyde (entry 11).
On the mechanism of this a-selective allylation (Scheme 1),
we assume that the key is conversion of allylboronates 2 into
Z-allylzincate species 6 (via 7, g-addition), which could
immediately react with aldehydes 1 to afford 8 (via g-addition);
thus, two g-additions could result in providing a-addition
products. Water could facilitate regeneration of the zinc
catalyst from 8. ESI-mass spectra of a mixture of Zn(OH)2
with 3c and 2a (see Table 1) showed a signal that corresponded
to 9, although the position and geometry of the methyl group
were unknown. According to the mechanism proposed, it
should be noted that the Zn-catalyzed reactions proceed much
faster than background (non-catalyzed) reactions.11
Regarding the a-substituted allylboronates, not only 2a but
ethyl- (2b), butyl- (2c), and i-butyl- (2d) substituted allyl-
boronates reacted smoothly to afford a-adducts 4 exclusively
in high yields with high syn-selectivities (entries 12–14).
We then surveyed the possibility of asymmetric cata-
lysis using Zn(OH)2 and chiral ligands (Scheme 2). In the
presence of Zn(OH)2 (10 mol%) and chiral bipyridine ligand
10 (12 mol%),12 benzaldehyde (1a) reacted with 2a in
Scheme 1 Possible formation of allylzincate 6.
Scheme 2 Preliminary results of asymmetric catalysis.
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H2O–CH3CN (1/4) to afford the a-addition product 4a in 39%
yield with high syn-selectivity, and the enantiomeric excess of
the syn-adduct was 66%. In this reaction, a certain amount of
g-adduct 5a was also produced (36% yield). On the other
hand, a-ketoester 11 reacted with 2a smoothly in the presence
of Zn(OH)2 (5 mol%) and chiral diamine ligand 12 (6 mol%)13
to afford the corresponding a-addition product 1314 in 92%
yield. No g-addition product was produced under these
conditions. It is noteworthy that the anti-adduct was obtained
in high diastereoselectivity with promising enantiomeric
excess.
3 N. Miyaura and Y. Yamamoto, in Comprehensive Organometallic
Chemistry III, ed. P. Knochel, Elsevier, Oxford, UK, 2007, vol. 9,
p. 145.
4 R. W. Hoffmann and H.-J. Zeib, J. Org. Chem., 1981, 46, 1309.
5 R. W. Hoffmann and B. Landmann, Chem. Ber., 1986, 119, 1039.
6 (a) J. W. Kennedy and D. G. Hall, J. Am. Chem. Soc., 2002, 124,
11586; (b) T. Ishiyama, T. Ahiko and N. Miyaura, J. Am. Chem.
Soc., 2002, 124, 12414; (c) D. G. Hall, Synlett, 2007, 1644.
7 In the crotylboration of aldehydes, examples to provide 4-substituted
homoallylic alcohols via g-addition-[3,3]-sigmatropic rearrangement
were reported. P. V. Ramachandran, D. Pratihar and D. Biswas,
Chem. Commun., 2005, 1988.
8 M. Fujita, T. Nagano, U. Schneider, T. Hamada, C. Ogawa and
S. Kobayashi, J. Am. Chem. Soc., 2008, 130, 2914.
9 In all cases, conversion of 4a into 5a or of 5a into 4a was not
observed. Moreover, no isomerization of 2a to crotylboronate
species occurred under the conditions.
10 In the reactions of specific allylstannanes with aldehydes, a-addition
products were obtained in organic solvents in the presence of a
stoichiometric amount of a Lewis acid (SnCl4, TiCl4, InCl3).
In summary, we have found very rare, a-selective allylation
reactions of allylboronates with aldehydes. The use of Zn(OH)2
with ligand 3c as a catalyst in aqueous media is a key in these
reactions. Preliminary results of asymmetric catalysis using
chiral ligands have also been demonstrated. We are now
investigating the role of the ligand and water toward
full elucidation of the mechanism of these unique a-selective
allylation reactions of allylboronates with aldehydes.
This work was partially supported by a Grant-in-Aid for
Science Research from the Japan Society for the Promotion of
Science (JSPS).
(a) T. Kramer, J.-R. Schwark and D. Hoppe, Tetrahedron Lett.,
¨
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E. J. Thomas, Tetrahedron: Asymmetry, 1995, 6, 2579.
11 In the reactions of crotylboronates with benzaldehyde, back-
ground (non-catalyzed) reactions seem to be faster. Boron–zinc
transmetalation (from 2 to 6) may be slow due to steric reason.
More details are under investigations.
12 (a) C. Bolm, M. Zehnder and D. Bur, Angew. Chem., Int. Ed., 1990,
29, 205; (b) C. Bol, M. Ewald, M. Felder and G. Schlingloff, Chem.
Ber., 1992, 125, 1169; (c) S. Ishikawa, T. Hamada, K. Manabe and
S. Kobayashi, Synthesis, 2005, 2176.
13 (a) H. Mimoun, J. Y. S. Laumer, L. Giannini, R. Scopelliti and
C. Floriani, J. Am. Chem. Soc., 1999, 121, 6158; (b) S. Kobayashi,
T. Hamada and K. Manabe, J. Am. Chem. Soc., 2002, 124,
5640.
14 The absolute configuration was determined to be 2S,3S after con-
verting to 2,3-dimethylpentane-1,2-diol. R. Riccio, M. Santaniello,
G. Squillace and L. Minale, J. Chem. Soc., Perkin Trans. 1, 1989,
823. See ESIw.
Notes and references
1 (a) A. Hosomi and H. Sakurai, Tetrahedron Lett., 1976, 17, 1295;
(b) A. Hosomi and K. Miura, in Comprehensive Organometallic
Chemistry III, ed. P. Knochel, Elsevier, Oxford, UK, 2007, vol. 9,
p. 297.
2 (a) Y. Yamamoto, H. Yatagai, Y. Naruta and K. Maruyama,
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E. P. Boden and E. J. Enholm, Tetrahedron Lett., 1984, 25, 3927;
(c) A. Baba, I. Shibata and M. Yasuda, in Comprehensive Organo-
metallic Chemistry III, ed. P. Knochel, Elsevier, Oxford, UK, 2007,
vol. 9, p. 341.
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This journal is The Royal Society of Chemistry 2010
1262 | Chem. Commun., 2010, 46, 1260–1262