TBOxCrIIICl-catalyzed enantioselective synthesis of 1,3-butadien-2-ylcarbinols

Article abstract of DOI:10.1021/ol801452c

(Chemical Equation Presented) A highly enantioselective synthesis of 1,3-butadien-2-ylcarbinols is achieved by using the TBOxCr^IIICl catalyst and homoallenylbromide 1. This method can be further extended to the enantio- and regioselective propargylation of aldehydes.

Full text of DOI:10.1021/ol801452c

ORGANIC
LETTERS
TBOxCrIIICl-Catalyzed Enantioselective
Synthesis of 1,3-Butadien-2-ylcarbinols
Marina Naodovic, Guoyao Xia, and Hisashi Yamamoto*
2008
Vol. 10, No. 18
4053-4055
Department of Chemistry, The UniVersity of Chicago, 5735 South Ellis AVenue,
Chicago, Illinois 60637
yamamoto@uchicago.edu
Received July 13, 2008
ABSTRACT
A highly enantioselective synthesis of 1,3-butadien-2-ylcarbinols is achieved by using the TBOxCrIIICl catalyst and homoallenylbromide 1. This
method can be further extended to the enantio- and regioselective propargylation of aldehydes.
2-Substituted-1,3-dienes, of general structure 2, represent an
increasingly important group of compounds due to their
synthetic versatility. These molecules are highly useful
precursors for the synthesis of several natural products.1 One
of the highly useful features of this class of compounds is
the 1,3-diene moiety that can be utilized for the construction
of functionalized cyclohexene rings.2 Besides the obvious
Diels-Alder reaction, alkyl(1,3-butadien-2- yl)carbinols have
been successfully used in various other reactions.3
Until the present day, several protocols for the synthesis
of this type of compounds have been published and they
can be classified into two general classes. One of the
pathways entails generation of 1,3-butadienyl-2-metal re-
agents which then add to a carbonyl group.4 Another
approach to 1,3-butadien-2-carbinols is based on the utility
of 2,3-butadienyl-1-metal reagents.5 Some of these methods
suffer from difficulties associated with low regioselectivity
and/or reactivity. In some instances, the protocol requires
starting materials which are prepared in several synthetic
steps, thereby rendering the method more tedious. Another
drawback of some methods is the use of toxic reagents, such
as tin compounds, as a source of the 1,3-butadiene moiety.
More recently, conceptually different methods for the
preparation of 1,3-butadien-2-carbinol derivatives have been
introduced.6 In 2005, Alcaraz and co-workers reported the
double homologation of 2,3-epoxy-1-bromides using dim-
(1) (a) Shen, Y.-C.; Wang, L.-T.; Wang, C.-H.; Khalil, A. T.; Guh, J.-
H. Chem. Pharm. Bull 2004, 52, 108. (b) Prakash, C. V. S.; Hoch, J. M.;
Kingston, D. G. I. J. Nat. Prod. 2002, 65, 100. (c) Iwamoto, M.; Ohtsu,
H.; Tokuda, H.; Hishino, H.; Matsunaga, S.; Tanaka, R. Bioorg. Chem.
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2002, 67, 1925. (b) Bear, R. B.; Sparks, S. M.; Shea, K. J. Angew. Chem.,
Int. Ed. 2001, 40, 820. (c) Bloch, R.; Chaptal-Gradoz, N. J. Org. Chem.
1994, 59, 4162. (d) Hatekeyama, S.; Sugawara, K.; Takano, S. Chem.
Commun. 1992, 953. (e) Wender, P. A.; Tebbe, M. J. Synthesis 1991, 1089.
(f) Wada, E.; Kanemasa, S.; Sakoh, H. Chem. Lett. 1984, 709. (g) Tuge,
O.; Wada, E.; Kanemasa, S.; Sakoh, H. Chem. Lett. 1984, 469.
(3) (a) Manane, V.; Gress, T.; Krause, H.; Fu¨rstner, A. J. Am. Chem.
Soc. 2004, 126, 8654. (b) Alcaide, B.; Almendros, P.; Campo, T. M.-D.;
Rodriguez-Acebes, R. Tetrahedron Lett. 2004, 45, 6429. (c) Bertolini, T. M.;
Nguyen, Q. H.; Harvey, D. F. J. Org. Chem. 2002, 67, 8675. (d) Taylor,
R. E.; Hearn, B. R.; Ciavarri, J. P. Org. Lett. 2002, 4, 2953. (e) Xiang,
A. X.; Watson, D. A.; Ling, T.; Theodorakis, E. A. J. Org. Chem. 1998,
63, 6774. (f) Hatekayama, S.; Yoshida, M.; Esumi, T.; Iwabuchi, Y.; Irie,
H.; Kawamoto, T.; Yamada, H.; Nishiazawa, M. Tetrahedron Lett. 1997,
38, 7887. (g) Hatekayama, S.; Sugawara, K.; Takanao, S. Tetrahedron Lett.
1991, 32, 4513.
(4) (a) Luo, M.; Iwabuchi, Y.; Hatekayama, S. Synlett 1999, 1109. (b)
Nataivi, C.; Taddei, M. Tetrahedron 1989, 45, 1131. (c) Brown, P. A.;
Jenkins, P. R. J. Chem. Soc., Perkin Trans. 1 1986, 1129. (d) Wada, E.;
Kanemasa, S.; Fujiwara, I.; Tsuge, O. Bull. Chem. Soc. Jpn. 1985, 58, 1942.
(e) Brown, P. A.; Jenkings, P. R. Tetrahedron Lett. 1982, 23, 3733. (f)
Nunomoto, S.; Sugawara, K.; Takano, S. Tetrahedron Lett. 1979, 44, 4788.
(5) (a) Yu, C.-M.; Lee, S.-J; Jeon, J. J. Chem. Soc., Perkin Trans. 1
1999, 3557. (b) Luo, M.; Iwabuchi, Y.; Hatekayama, S. Chem. Commun.
1999, 267. (c) Soundararajan, R.; Li, G.; Brown, C. H. J. Org. Chem. 1996,
61, 100. (d) Hatekayama, S.; Sugawara, K.; Kawmura, M.; Takano, S.
Tetrahedron Lett. 1991, 32, 4509.
10.1021/ol801452c CCC: $40.75
Published on Web 08/15/2008
2008 American Chemical Society

ethylsulfonium methylide to generate 1,3-butadien-2-
ylcarbinols.6a The terminal alkyne-ethylene cross metathesis
approach described by Diver et al. can also be used
successfully for the synthesis of dienyl acetates and silyl and
benzyl ether derivatives.6b,c Chan’s report of an indium-based
Barbier-type of reaction between 1,4-dibromo-2-butyne and
aldehyde in aqueous media is noteworthy from the standpoint
of atom economy and environmental issues.6d
Among the aforementioned accounts, there are only a few
reports of enantioselective transformations.5a,c,d,6a,b,e Even
though these reactions provide products with high yields and
enantioselectivities, the scope of the substrates is not
extensive.
We wish to report an enantioselective synthesis of 1,3-
butadien-2-ylcarbinols using tethered bis(8-quinolinato) (TBOx)
chrominum complex (TBOxCrIIICl) and bromoallene 1.
The TBOxCrIIICl catalyst, developed in our group, was
shown to be a highly effective catalyst for several asymmetric
redox processes.7 On the basis of the catalytic redox Cr(II)/
Cr(III)-Mn system pioneered by Fu¨rstner et al.,8 TBOx-
CrIIICl catalyst efficiently promotes a pinacol coupling
reaction of aldehydes,7a asymmetric Nozaki-Hiyama ally-
lation reaction of aldehydes,7b and allenylation reaction of
aldehydes.7c These reactions proceed exceedingly well with
use of low catalyst loadings to yield products in a highly
diastereo-/enantioselective fashion.
Table 1. Optimization of Reaction Conditionsa
entry
solvent
MeCN
DME
MeCN:DME (1:3)
THF
yield (%)b
ee (%)c
1
2
3
4
37
35
40
41
86
87
84
90
a Reactions were carried out with 2.0 equiv of 1, 1.0 equiv of PhCHO,
3.0 equiv of Mn, and 1.0 equiv of TESCl. b Yields of the isolated products.
c Determined by HPLC analysis.
poor aldehydes which exhibited decreased reactivity. Gen-
erally, high levels of enantioselectivity were maintained for
all of the carbonyl substrates used.
Encouraged by the high regioselectivity observed in the
dienylation reaction, we were interested in the reactivity of
simple propargyl bromide as a substrate for Cr-catalyzed
reaction. Interestingly, the formation of (R)-homopropargyl
alcohol of benzaldehyde occurred exclusively (Scheme 1).
Therefore the TBOxCrIIICl-Mn system can be effectively
employed in an enantioselective propargylation of aldehydes.
Comparison of the optical rotation value with previously
published data revealed that products have (R)-absolute
Encouraged by the reactivity of our catalyst with allyl-
and propargylhalide substrates, we have turned our attention
to bromoallene 1 as an alternative substrate for the Cr-
catalyzed reactions.
We were interested in exploring the reactivity of bromoal-
lene 1 in Cr-catalyzed addition to aldehydes, since it presents
a more challenging substrate due to the possible formation
of regioisomers. To our surprise, when bromoallene 1 was
treated with TBOxCrIIICl-Mn in the presence of benzalde-
hyde and TESCl only the 1,3-butadiene product was ob-
served. Screening of the solvents commonly used with this
catalytic system (Table 1, enteries 1-4) showed THF to be
the most effective affording the product with highest yields
and ee values (entry 4). Further investigation of the reaction
conditions indicated that 2.0 equiv of bromoallene provided
2 in slightly higher yield.
Table 2. Scope of the Dienylation Reactiona
With these optimized conditions, reactions with several
aldehydes have been carried out and the results are sum-
marized in Table 2.
The reaction proceeded well for a series of aldehydes
providing adducts with good to moderate yields and high
enantioselectivities. Electron-rich aldehydes afford 2-substi-
tuted 1,3-butadienes with higher yields in contrast to electron-
(6) (a) Alcaraz, L.; Cox, K.; Cridland, A. P.; Kinchin, E.; Morris, J.;
Thompson, S. P. Org. Lett. 2005, 7, 1399. (b) Smulik, J. A.; Diver, S. T.
J. Org. Chem. 2000, 65, 1788. (c) Smulik, J. A.; Diver, S. T. Org. Lett.
2000, 2, 2271. (d) Lu, W.; Ma, J.; Yang, Y.; Chan, T. H. Org. Lett. 2000,
2, 3469. (e) Alcaide, B.; Almendros, P.; Campo, T. M.; Rodr´ıguez-Acebes,
R. Tetrahedron Lett. 2004, 45, 6429. (f) Katritzky, A. R.; Serdyuk, L.;
Toader, D.; Wang, X. J. Org. Chem. 1999, 64, 1888.
a Reactions were carried out with 2.0 equiv of bromoallene 1, 1.0 equiv
of aldehyde, 3.0 equiv of Mn, and 1.1 equiv of TESCl. b Yields of the
isolated products. c Determined by HPLC analysis with Chiracel OB-H
column.
(7) (a) Takenaka, N.; Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2004,
126, 13198. (b) Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 2554.
(c) Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 496. (d) Xia, G.;
Yamamoto, H. Chem. Lett. 2007, 1082.
(8) Fu¨rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 2533.
4054
Org. Lett., Vol. 10, No. 18, 2008

center of the resulting cis-ꢀ complex is chiral and two of
the coordination sites are nonequivalent. Owing to the C2-
symmetry of the ligand we do not need to worry about the
possible generation of two stereoisomers.
Scheme 1
.
Highly Regioselective Propargylation of
Benzaldehyde
Considering the geometry of the cis-ꢀ configuration of the
metal center, two transition states that lead to (R)-alcohols
can be envisioned (Figure 2). In the transition state A, the
allenyl moiety is bonded axially to chromium while the
aldehyde adopts an equatorial orientation. Clearly, the
aldehyde coordinates to chromium through its oxygen
electron pair in the trans manner to the aldehyde’s R-group.
In such a spatial arrangement, nucleophilic attack of the
dienyl moiety occurs at the Re-face of the aldehyde to deliver
(R)-alcohol. The transition state B involves opposite coor-
dination of the substrates. More specifically, the allenyl
moiety is now bonded to chromium in the equatorial position
and aldehyde adopts the axial position. In this assembly,
aldehyde coordinates to the metal center in a similar fashion
as in A leaving its Re-face open for the addition of dienyl
moiety (Figure 2).
configuration. This observation is consistent with our results
of the allylation7b and allenylation7c reactions of aldehydes
catalyzed by (R)-TBOxCrIIICl. On the basis of these observa-
tions we could propose two plausible transition states that
could occur during the reaction (Figure 2).
A noteworthy feature of this reaction is high regioselec-
tivity for the addition of organochromium species. In our
previous studies regarding SEi′ processes for propargyl and
allenyl metal reagents, intermediate organometallic species
generated from trimethylsilyl-substituted alkynes reacted at
their less hindered site.9 In contrast to those accounts, here
we observe the formation of 1,3-butadienyl products which
arise exclusively from the addition of organochromium
intermediate where chromium is located at a more sterically
hindered site.
Figure 1. Possible geometries of the octahedral chromium center
in TBOxCrIIICl complex.
TBOxCrIIICl may have a total of three geometric isomers
(Figure 1), given that it adapts octahedral coordination geometry.
In summary, we have developed a method for the
enantioselective synthesis of 1,3-diene-2-ylcarbinols using
chiral tethered bis(8-quinolinato) ligand (TBOxH) developed
in our laboratory. The protocol described provides products
with high ee values and moderate yields under mild reaction
conditions. The TBOxCrIIICl catalyst circumvents the dif-
ficulties generally associated with the regioselectivity of the
reaction. Furthermore, the method does not require the use
of toxic reagents used in previous enantioselective syntheses
of this class of compounds.
Acknowledgment. We thank the National Science Foun-
Figure 2. Possible transition states leading to (R)-alcohols
dation (NSF) for the financial support of this research.
Supporting Information Available: Experimental pro-
cedures and spectral data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
The X-ray structures of rac-TBOxCrCl revealed that TBOxH
ligand is bound to the chromium center in a cis-ꢀ configuration.
The crystal structure of TBOx(EtOH)2CrIIICl also showed that
the two reactive sites are positioned cis to each other and fit
closely into the concave site of the TBOxCrIII complex.7a
Although the free TBOxH ligand has C2-symmetry, the
produced cis-ꢀ metal complex does not. Thus, the metal
OL801452C
(9) (a) Yamakado, Y.; Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Am.
Chem. Soc. 1981, 103, 5568. (b) Ishiguro, M.; Ikeda, N.; Yamamoto, H. J.
Org. Chem. 1982, 47, 2227.
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