Rhodium-catalyzed kinetic resolution of tertiary homoallyl alcohols via stereoselective carbon-carbon bond cleavage

Article abstract of DOI:10.1021/ol800120p

A nonenzymatic kinetic resolution of tertiary homoallyl alcohols has been developed through a rhodium-catalyzed retro-allylation reaction under simple conditions. Selectivity factors of up to 12 have been achieved by employing (R)-H₈-binap as the Iigand, and the reaction can be conducted on a preparative scale.

Full text of DOI:10.1021/ol800120p

ORGANIC
LETTERS
2008
Vol. 10, No. 6
1191-1193
Rhodium-Catalyzed Kinetic Resolution
of Tertiary Homoallyl Alcohols via
Stereoselective Carbon
Cleavage
−Carbon Bond
Ryo Shintani,* Keishi Takatsu, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo,
Kyoto 606-8502, Japan
shintani@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Received January 18, 2008
ABSTRACT
A nonenzymatic kinetic resolution of tertiary homoallyl alcohols has been developed through a rhodium-catalyzed retro-allylation reaction
under simple conditions. Selectivity factors of up to 12 have been achieved by employing (R)-H8-binap as the ligand, and the reaction can be
conducted on a preparative scale.
Nonenzymatic kinetic resolution of racemic secondary alco-
hols has been extensively investigated in the past few decades
and has reached its mature stage.1,2 In contrast, the corre-
sponding kinetic resolution of tertiary alcohols has been much
less studied, and to the best of our knowledge, there are only
two effective nonenzymatic catalyst systems available to date.
Thus, Miller developed peptide-based organocatalysts for
enantioselective acylation of tertiary alcohols bearing an
acetamido group at the â-carbon,3 and Matsunaga and
Shibasaki recently described the use of mixed La/Li hetero-
bimetallic catalysts for the kinetic resolution of tertiary
alcohols having a nitro group at the â-carbon through a retro-
nitroaldol reaction.4 To remedy this methodological defi-
ciency, we envisioned that efficient kinetic resolution might
be achieved by late transition metal-catalyzed stereoselective
cleavage of an R,â-carbon-carbon bond in racemic tertiary
alcohols. In particular, here we focus on utilizing the retro-
allylation approach under transition-metal catalysis,5,6 and
we demonstrate that a Rh/(R)-H8-binap complex can effec-
tively catalyze kinetic resolution of tertiary homoallyl alco-
hols under simple reaction conditions (eq 1).
(1) For reviews, see: (a) Kagan, H. B.; Fiaud, J. C. Top. Stereochem.
1988, 18, 249. (b) Vedejs, E.; Jure, M. Angew. Chem., Int. Ed. 2005, 44,
3974. (c) Robinson, D. E. J. E.; Bull, S. D. Tetrahedron: Asymmetry 2003,
14, 1407. See also: (d) Fu, G. C. Acc. Chem. Res. 2000, 33, 412.
(2) For recent progress, see: (a) Rendler, S.; Auer, G.; Oestreich, M.
Angew. Chem., Int. Ed. 2005, 44, 7620. (b) Birman, V. B.; Li, X.; Jiang,
H.; Uffman, E. W. Tetrahedron 2006, 62, 285. (c) MacKay, J. A.; Vedejs,
E. J. Org. Chem. 2006, 71, 498. (d) Mazet, C.; Roseblade, S.; Ko¨hler, V.;
Pfaltz, A. Org. Lett. 2006, 8, 1879. (e) Li, Y.-Y.; Zhang, X.-Q.; Dong,
Z.-R.; Shen, W.-Y.; Chen, G.; Gao, J.-X. Org. Lett. 2006, 8, 5565.
(3) (a) Jarvo, E. R.; Evans, C. A.; Copeland, G. T.; Miller, S. J. J. Org.
Chem. 2001, 66, 5522. (b) Angione, M. C.; Miller, S. J. Tetrahedron 2006,
62, 5254.
In an initial investigation, we employed racemic 2-phenyl-
4-penten-2-ol (1a) as a model homoallyl alcohol and con-
(4) Tosaki, S.; Hara, K.; Gnanadesikan, V.; Morimoto, H.; Harada, S.;
Sugita, M.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem.
Soc. 2006, 128, 11776.
(5) Rhodium catalysis: (a) Takada, Y.; Hayashi, S.; Hirano, K.;
Yorimitsu, H.; Oshima, K. Org. Lett. 2006, 8, 2515. (b) Jang, M.; Hayashi,
S.; Hirano, K.; Yorimitsu, H.; Oshima, K. Tetrahedron Lett. 2007, 48, 4003.
10.1021/ol800120p CCC: $40.75
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Published on Web 02/28/2008

ducted a rhodium-catalyzed retro-allylation reaction with
various chiral phosphine ligands (Table 1). On the basis of
5.3), albeit in lower reactivity (49% conversion after 17 h;
entry 4). The change of (R)-binap to its analogues, (R)-
segphos11 and (R)-H8-binap,12 led to further improvement
of stereoselectivity (s ) 6.8 and s ) 7.0, respectively;
entries 5 and 6). The absolute configuration of remaining
1a in entry 6 (89% ee) was determined to be (R) by com-
parison of the optical rotation with the reported value in the
literature.13
Table 1. Rhodium-Catalyzed Kinetic Resolution of (()-1a:
Ligand Effect
Under these conditions with (R)-H8-binap as a ligand,
several tertiary homoallyl alcohols can be kinetically resolved
through retro-allylation (Table 2). Thus, 2-(2-naphthyl)-4-
entry
ligand
time (h)
ee of resolved 1aa
17% ee (S) (49% convn) 1.7
1% ee (S) (66% convn) 1.0
25% ee (S) (70% convn) 1.5
51% ee (R) (49% convn) 5.3
52% ee (R) (46% convn) 6.8
89% ee (R) (67% convn) 7.0
sb
1c
2c
3c
4
5
6
(R)-MeO-mop
(S)-(R)-ppfa
(+)-nmdpp
(R)-binap
(R)-segphos
(R)-H8-binap
0.5
1.5
1.5
17
17
17
Table 2. Rhodium-Catalyzed Kinetic Resolution of (()-1:
Scope
a The ee was determined by chiral HPLC after purification and the
conversion was dermined by crude 1H NMR against internal standard (1,4-
dimethoxybenzene). b s ) ln{(1 - c)(1 - ee)}/ln{(1 - c)(1 + ee)} where
c is the conversion of 1a and ee is the ee of remaining 1a. c 11 mol % of
ligand was used.
the report by Yorimitsu and Oshima where monodentate
phosphines are effective ligands on rhodium catalysts for
retro-allylation,5 we started our study by using chiral
monodentate phosphine ligands, such as (R)-MeO-mop,7 (S)-
(R)-ppfa,8 and (+)-nmdpp.9 As expected, retro-allylation of
(()-1a smoothly proceeded in the presence of 5 mol % of
rhodium/monophosphine catalyst in toluene at 120 °C,
reaching 49-70% conversions within 90 min (entries 1-3).
Unfortunately, however, these chiral ligands could not
effectively distinguish between the two enantiomers of 1a,
resulting in almost nonselective processes (s ) 1.0-1.7). In
contrast, we found that the use of (R)-binap,10 a chiral
bisphosphine ligand, induced higher enantioselectivity (s )
a The ee was determined by chiral HPLC after purification and the
conversion was dermined by crude 1H NMR against internal standard (1,4-
dimethoxybenzene). b s ) ln{(1 - c)(1 - ee)}/ln{(1 - c)(1 + ee)} where
c is the conversion of 1 and ee is the ee of remaining 1. c The reaction was
conducted at 100 °C.
penten-2-ol (1b) gave the resolved alcohol in 88% ee at 68%
conversion (s ) 6.4; entry 2) and 2-(1-naphthyl)-4-penten-
2-ol (1c) gave 94% ee at 67% conversion (s ) 8.8; entry 3).
Somewhat better selectivity factor (s ) 11) was observed
when 1c was resolved at 100 °C (entry 4). In addition to
these 2-aryl-4-penten-2-ols, alkyl-substituted alcohol 1d was
also resolved with reasonably high efficiency (s ) 5.1; entry
5). Other homoallyl alcohols such as cyclic alcohol 1e and
aryl alkenyl carbinol 1f were employed as well, achieving s
) 5.4 and s ) 4.0, respectively (entries 6 and 7). It is worth
(6) Ruthenium catalysis: (a) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada,
T.; Morisaki, Y.; Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120,
5587. Palladium catalysis: (b) Hayashi, S.; Hirano, K.; Yorimitsu, H.;
Oshima, K. J. Am. Chem. Soc. 2006, 128, 2210. (c) Iwasaki, M.; Hayashi,
S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129,
4463.
(7) (a) Hayashi, T. Acc. Chem. Res. 2000, 33, 354. (b) Uozumi, Y.;
Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945.
(8) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.; Nagashima,
N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi, M.; Yamamoto,
K.; Kumada, M. Bull. Chem. Soc. Jpn. 1980, 53, 1138.
(11) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. AdV. Synth. Catal. 2001, 343, 264.
(12) Zhang, X.; Mashima, K.; Koyano, K.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Takaya, H. Tetrahedron Lett. 1991, 32, 7283.
(13) Soai, K.; Ishizaki, M.; Yokoyama, S. Chem. Lett. 1987, 341.
(9) Morrison, J. D.; Masler, W. F. J. Org. Chem. 1974, 39, 270.
(10) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi,
H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629.
1192
Org. Lett., Vol. 10, No. 6, 2008

noting that the results shown here represent rare examples
where significantly high enantioselectivity is observed in the
asymmetric reactions at as high as 120 °C.
On the basis of the absolute configuration of the unreacted
alcohol, a proposed catalytic cycle of this process with
substrate 1a is illustrated in Scheme 1. Thus, alkoxorhodium
Of course, the present catalysis can be easily scaled up as
shown in eq 2. Thus, 5.0 mmol of (()-1c was subjected to
the Rh/(R)-H8-binap-catalyzed retro-allylation at 100 °C,
giving resolved 1c in 97% ee at 65% conversion (s ) 12).
Scheme 1. Proposed Catalytic Cycle for the
Rhodium-Catalyzed Kinetic Resolution of (()-1a
(Rh ) Rh((R)-H8-binap)).
In summary, we have developed a rhodium-catalyzed
kinetic resolution of tertiary homoallyl alcohols under simple
reaction conditions. High selectivity factors have been
achieved by employing (R)-H8-binap as the ligand and the
reaction can be conducted on a preparative scale. Future
studies will explore further improvement of the reaction
conditions and expansion of the substrate scope.
Acknowledgment. Support has been provided in part by
a Grant-in-Aid for Scientific Research, the Ministry of
Education, Culture, Sports, Science and Technology, Japan
(the Global COE Program “Integrated Materials Science”
on Kyoto University).
species A derived from (S)-1a preferentially undergoes retro-
allylation to give acetophenone and allylrhodium species B.
The allyl-moiety of intermediate B is then protonated through
ligand exchange with (S)-1a, regenerating alkoxorhodium A
and leaving (R)-1a behind.
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL800120P
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