Acceleration effect of Lewis acid in allylboration of aldehydes: Catalytic, regiospecific, diastereospecific, and enantioselective synthesis of homoallyl alcohols

Article abstract of DOI:10.1021/ja0210345

The addition of pinacol allylboronic esters to aromatic and aliphatic aldehydes smoothly occurred at -78 °C in toluene in the presence of a catalytic amount of AlCl₃ or Sc(OTf)₃ (10 mol %) to give the corresponding homoallyl alcohols in high yields. The reactions proceeded regio- and diastereospecifically, yielding the isomerically pure syn- and anti-homoallyl alcohols from (Z)- and (E)-allylboronic esters, respectively. The protocol was also applied to enantioselective reactions by using a chiral Lewis acid catalyst. Copyright

Full text of DOI:10.1021/ja0210345

Published on Web 09/27/2002
Acceleration Effect of Lewis Acid in Allylboration of Aldehydes: Catalytic,
Regiospecific, Diastereospecific, and Enantioselective Synthesis of Homoallyl
Alcohols†
Tatsuo Ishiyama,* Taka-aki Ahiko, and Norio Miyaura*
Contribution from the DiVision of Molecular Chemistry, Graduate School of Engineering, Hokkaido UniVersity,
Sapporo 060-8628, Japan
Received July 29, 2002
Table 1. Lewis Acid-Catalyzed Allylboration of Aldehydes with 2a
(R2, R3 ) H) (eq 1)a
Lewis acid-catalyzed addition of allylsilicon and -tin reagents
to carbonyl compounds is a most important and powerful tool to
construct a regio- and stereodefined carbon framework.1 The
reactions generally proceed in an SE2′ manner through an acyclic
transition state to provide syn-homoallyl alcohols regiospecifically
and diastereoselectively when using γ-substituted reagents. Another
efficient candidate for the synthesis of regio- and stereodefined
homoallyl alcohols is the addition of allylboron reagents, which
takes place regio- and diastereospecifically through a chairlike six-
membered cyclic transition state in the absence of a Lewis acid.2
Namely, one major advantage of the allylboration over the
allylsilation and -stannation is that both syn- and anti-homoallyl
alcohols can be obtained with high isomeric purities from (Z)- and
(E)-allylboron reagents, respectively.3 On the other hand, allylsi-
lation and -stannation are superior to allylboration with respect to
enantioselective synthesis because the former reactions only require
a catalytic amount of a chiral source.4 We presumed that if a Lewis
acid could catalyze allylboration while maintaining the chairlike
six-membered cyclic transition state, the reaction would allow a
catalytic, regiospecific, diastereospecific, and enantioselectiVe
approach to homoallyl alcohols.5 However, to our knowledge, there
is no report concerning the effects of Lewis acids in the allylboration
of carbonyl compounds.6 We disclose herein the acceleration effect
of Lewis acids in the regio- and diastereospecific addition of pinacol
allylboronic esters (2) to aldehydes (1) to give the corresponding
homoallyl alcohols (3), as well as the preliminary results of an
extension of the protocol toward catalytic enantioselective reactions
(eq 1).
b
yield/%
entry
aldehyde 1
AlCl3
Sc(OTf)3
1
2
3
4
5
6
7
4-CF3C6H4CHO
PhCHO
4-MeC6H4CHO
4-MeOC6H4CHO
n-C10H21CHO
c-C6H11CHO
80 (16 h)
88 (16 h)
47 (24 h)
82 (36 h)
54 (16 h)
48 (16 h)
69 (24 h)
69 (16 h)
80 (16 h)
62 (24 h)
84 (36 h)
73 (16 h)
74 (16 h)
74 (24 h)
(E)-PhCHdCHCHO
a Allylboration of an aldehyde (1.0 mmol) with 2a (1.1 mmol) in the
presence of a Lewis acid (0.1 mmol) in toluene (6 mL) at -78 °C for the
period shown in the table was followed by treatment of the resulting mixture
with DIBAH (2.0 mmol) at the temperature for 1 h. b Isolated yields based
on aldehydes.
activity. Although the addition did not proceed at all in the absence
of a Lewis acid, AlCl3 (88%), Sc(OTf)3 (80%), TiCl4 (63%), BF3‚
OEt2 (56%), and SnCl4 (30%) all catalyzed the reaction to afford
the corresponding homoallyl alcohol. The high catalytic activity
of Sc(OTf)3 is notable from the view of practical usefulness, because
it can be handled in air without special precautions.8 A series of
the reaction was also investigated in CH2Cl2, and the yields were
comparable to those of the reaction in toluene.
To examine the scope and limitations of the Lewis acid-catalyzed
allylboration, the addition of 2a to representative 1 was carried out
in the presence of an AlCl3 or a Sc(OTf)3 catalyst. The results are
summarized in Table 1. Either aromatic (entries 1-4) or aliphatic
(entries 5 and 6) 1 are viable substrates to produce the corresponding
3 in high yields. R,â-Unsaturated 1 also underwent the 1,2-addition
selectively (entry 7). The addition catalyzed by Sc(OTf)3 provided
better yields than that by AlCl3 in most cases. Especially, the Sc-
(OTf)3 catalyst was effective for the reaction of sterically hindered
1 (entry 6). Electron-poor 1 (entry 1) exhibited higher reactivity
than electron-rich 1 (entry 4), the tendency of which is similar to
that in uncatalyzed allylboration.2 All attempts at the reaction of
pivalaldehyde were unsuccessful presumably due to its large steric
hindrance.
An example of the synthetic utility of the present method is
shown in eq 2. When a mixture of 4-(trifluoromethyl)benzaldehyde
(1.1 mmol) and 4-methoxybenzaldehyde (1.1 mmol) was allowed
to react with 2a (1.0 mmol) in the absence of a Lewis acid in toluene
(6 mL) at room temperature for 16 h, two homoallyl alcohols
resulting from the reaction with both aldehydes were obtained in a
ratio of 81:19. On the other hand, the AlCl3- or Sc(OTf)3-catalyzed
reaction at -78 °C provided an adduct of 4-(trifluoromethyl)-
benzaldehyde as the sole product. The results indicate the possibility
that stepwise transformations of formyl groups exhibiting different
Our initial studies were focused on elucidating the acceleration
effect of a Lewis acid. The allylboration of benzaldehyde (1.0
mmol) with pinacol 2-propenylboronic ester (2a) (1.1 mmol) in
the presence of a Lewis acid (0.1 mmol) in toluene (6 mL) at -78
°C for 16 h was followed by treatment of the mixture with DIBAH7
(2.0 mmol) at -78 °C for 1 h to trap an unreacted aldehyde. To
our surprise, most representative Lewis acids exhibited high catalytic
* Corresponding author. E-mail: ishiyama@org-mc.eng.hokudai.ac.jp.
† After our manuscript was submitted, we became aware of a related study by
Hall: Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc. 2002, 124. Published
ASAP, September 6, 2002.
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J. AM. CHEM. SOC. 2002, 124, 12414-12415
10.1021/ja0210345 CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
electrophilicity in a molecule can be completely controlled by the
present method.
Regio- and diastereochemistry of the AlCl3- or Sc(OTf)3-
catalyzed allylboration is shown in eq 3. As expected, the addition
of pinacol (E)- or (Z)-2-butenylboronic esters (2b or 2c) to
benzaldehyde occurred regio- and diastereospecifically to yield
isomerically pure anti- and syn-homoallyl alcohols from 2b and
2c, respectively. The results are quite different from those reported
in the allylsilation and -stannation.1 Although we have not studied
the reaction mechanism yet, the observed diastereochemistry
strongly suggests the allylboration through a chairlike six-membered
cyclic transition state similar to uncatalyzed reactions.2
Supporting Information Available: Experimental procedures and
spectral analyses of products (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) For reviews, see: (a) Fleming, I. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 2, p 563. (b)
Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207. (c) Colvin, E. W.
In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F.
G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford, 1995; Vol. 11, p
313.
(2) For reviews, see: (a) Roush, W. R. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 2, p 1. (b)
Matteson, D. S. Stereodirected Synthesis with Organoboranes; Springer:
Berlin, 1995. (c) Vaultier, M.; Carboni, B. In ComprehensiVe Organo-
metallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;
Pergamon Press: Oxford, 1995; Vol. 11, p 191.
(3) For diastereospecific allylsilation, see: (a) Hosomi, A.; Kohara, S.;
Tominaga, Y. J. Chem. Soc., Chem. Commun. 1987, 1517. (b) Cerveau,
G.; Chuit, C.; Corriu, R. J. P.; Reye, C. J. Organomet. Chem. 1987, 328,
C17. (c) Kira, M.; Kobayashi, M.; Sakurai, H. J. Am. Chem. Soc. 1988,
110, 4599. For diastereospecific allylstannation, see: (d) Servens, C.;
Pereyre, M. J. Organomet. Chem. 1972, 35, C20. (e) Yamamoto, Y.;
Maruyama, K.; Matsumoto, K. J. Chem. Soc., Chem. Commun. 1983, 489.
(4) For reviews, see: (a) Cozzi, P. G.; Tagliavini, E.; Umani-Ronchi, A. Gazz.
Chim. Ital. 1997, 124, 247. (b) Keck, G. E.; Krishnamurthy, D. Org. Synth.
1998, 75, 12. (c) Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 1999,
527. (d) Yanagisawa, A. In ComprehensiVe Asymmetric Catalysis I-III;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin,
1999; Vol. 2, p 965.
(5) For chiral Lewis base/allylic trichlorosilane approaches, see: (a) Denmark,
S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem. 1994, 59,
6161. (b) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J. Am. Chem.
Soc. 1998, 120, 6419. (c) Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi,
Y. Tetrahedron 1999, 55, 977. (d) Denmark, S. E.; Fu, J. J. Am. Chem.
Soc. 2001, 123, 9488 and references cited therein.
Finally, our preliminary results of catalytic, regiospecific, dia-
stereospecific, and enantioselective allylboration are depicted in eq
4. The addition of 2b to benzaldehyde catalyzed by Lewis acids
comprised of AlCl3 and (S)-BINOL gave a 1R,2R isomer in 39%
ee. The low enantioselectivity apparently is attributed to a competi-
tive reaction catalyzed by HCl which would be generated from the
reaction of AlCl3 with BINOL.9 The result prompted us to examine
dialkylaluminum chloride10 as a catalyst precursor that is expected
not to form HCl during the catalyst generation. Indeed, the
enantioselectivity was improved to 51% ee by using Et2AlCl, while
the rate of the reaction was much slower than that using the AlCl3-
based catalyst. In contrast, the allylboration did not take place at
all when using an Sc(OTf)3/(S)-BINOL catalyst.11 An Et2AlCl/(S)-
BINOL-catalyzed reaction of 2c was also examined; however, the
reaction resulted in 8% ee.
(6) (a) The related allyltrifluoroborate salts add to aldehydes using a strong
Lewis acid catalyst, while it is not a formal mode of Lewis acid
activation: Batey, R. A.; Thadani, A. N.; Smil, D. V.; Lough, A. J.
Synthesis 2000, 990. (b) Hoffmann and co-workers have reported
intramolecular allylboration of acetals, in which they have employed a
Lewis acid to hydrolyze the acetal moiety to aldehyde. Although they
have not discussed effects of the Lewis acids in the allylboration, the
reactions may be accelerated by them: Hoffmann, R. W.; Kru¨ger, J.;
Bru¨ckner, D. New J. Chem. 2001, 25, 102 and references cited therein.
(7) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Park, J. C. J. Org. Chem.
1990, 55, 4109.
(8) For a review, see: Kobayashi, S. Synlett 1994, 689.
In summary, we have found for the first time the acceleration
effect of a Lewis acid in allylboration of carbonyl compounds. The
protocol provides a catalytic, regiospecific, diastereospecific, and
enantioselectiVe method for the synthesis of homoallyl alcohols.
Further studies on the mechanism and improvement of enantiose-
lectivity are currently in progress in our laboratory.
(9) The addition of 2a (1.1 mmol) to benzaldehyde (1.0 mmol) in the presence
of HCl (0.1 mmol) in toluene/ether solvent (6 mL) at -78 °C for 16 h
resulted in a 21% yield of the corresponding homoallyl alcohol.
(10) Gothelf, A. S.; Hansen, T.; Jorgensen, K. A. J. Chem. Soc., Perkin Trans.
1 2001, 854.
(11) Kobayashi, S.; Araki, M.; Hachiya, I. J. Org. Chem. 1994, 59, 3758.
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