Stereoselective synthesis of α-allenols by rhodium-catalyzed reaction of alkynyl oxiranes with arylboronic acids

Article abstract of DOI:10.1002/anie.200701505

(Chemical Equation Presented) Better than Cu, Pd, and Fe catalysts: The rhodium-catalyzed reaction of alkynyl oxiranes with arylboronic acids provides synconfigured α-allenols with excellent diastereoselectivity. Precoordination of the oxygen atom of the

Full text of DOI:10.1002/anie.200701505

Angewandte
Chemie
DOI: 10.1002/anie.200701505
a-Allenol Synthesis
Stereoselective Synthesis of a-Allenols by Rhodium-Catalyzed
Reaction of Alkynyl Oxiranes with Arylboronic Acids**
Tomoya Miura, Masahiko Shimada, Sung-Yu Ku, Tomohiro Tamai, and Masahiro Murakami*
Allenes constitute an important class of building blocks
possessing axial chirality as well as unique reactivities.[1] The
SN2’-type substitution of propargylic alcohol derivatives with
organometallic reagents is one of the most reliable proce-
dures for the stereoselective preparation of substituted
allenes.[2] We previously described the rhodium-catalyzed
substitution reaction of propargylic acetates with phenyl-
boronic acid, wherein the resulting alkenylrhodium(I) inter-
mediate underwent b-oxygen elimination to afford a trisub-
stituted allene.[3] In an extension of this work we set out to
examine the use of alkynyl oxiranes as acceptors for
arylboronic acids owing to the considerable interest in the
resulting a-allenols as building blocks for the construction of
oxygenated heterocycles of biological and pharmacological
relevance.[4] We report herein on the rhodium-catalyzed
reaction of alkynyl oxiranes with arylboronic acids which
yields a-allenols with excellent diastereoselectivity.
Alkynyl oxirane 1a (1.0 equiv) was treated with phenyl-
boronic acid (2a, 1.5 equiv) in the presence of [{RhCl(nbd)}2]
(5 mol% of Rh, nbd = norborna-2,5-diene)[5] and KOH
(0.6 equiv) in THF (0.1m) at room temperature. The reaction
was completed in 2 h, and an extractive workup followed by
chromatographic isolation afforded the a-allenol 3aa in 81%
yield with excellent diastereoselectivity (syn/anti = 99:1)[6]
[Eq. (1)].
The highly stereoselective formation of the syn-config-
ured a-allenol is noteworthy among other SN2’-type reactions
of alkynyl oxiranes with organometallic reagents.[7] Organo-
copper and organocuprate reagents preferentially afford anti-
configured a-allenols in most cases[8] with very few excep-
tions.[9] Palladium-catalyzed reactions with organostan-
nanes[10] and organoborons[11] also give the corresponding
anti-substitution product. On the other hand, syn-configured
a-allenols were selectively produced by the iron-catalyzed
reaction of alkynyl oxiranes with Grignard reagents.[12]
However, the iron-catalyzed reaction of 1a with PhMgBr
exhibited only moderate diastereoselectivity (syn/anti =
66:34).
The mechanism shown in Scheme 1 explains the stereo-
selective formation of 3aa. Initially, a phenylrhodium(I)
species is generated by transmetalation of hydroxorhodium(I)
with 2a.[13] Then, cis 1,2-addition of the phenylrhodium(I)
species to 1a takes place to afford the alkenylrhodium(I)
intermediate A. Noteworthy was that addition of the phenyl-
rhodium(I) species across the carbon–carbon triple bond of
the epoxy-substituted alkyne, which otherwise required
heating over 808C,[14] occurred at room temperature. We
assume that precoordination of the oxygen atom of the
oxirane ring to rhodium contributes to the high stereoselec-
tivity as well as high reactivity, similar to the case of the iron-
catalyzed reaction.[12] Subsequent b-oxygen
elimination occurs in a syn mode to open the
oxirane ring.[15] The resulting rhodium(I) alk-
oxide B reacts with 2a to release the product
3aa along with a rhodium(I) boronate.[16]
Other examples of the stereoselective syn-
thesis of a-allenols 3 from various combina-
tions of alkynyl oxiranes 1 and arylboronic
acids 2 are listed in Table 1. The catalytic
[*] Dr. T. Miura, M. Shimada, S.-Y. Ku,[+] T. Tamai, Prof. Dr. M. Murakami
Department of Synthetic Chemistry andBiological Chemistry
Kyoto University
Katsura, Kyoto 615-8510 (Japan)
Fax: (+81)75-383-2748
E-mail: murakami@sbchem.kyoto-u.ac.jp
Homepage: http://www.sbchem.kyoto-u.ac.jp/murakami-lab
[+] Permanent address: Department of Chemistry
National Taiwan University (Taiwan)
[**] This work was supportedin part by a Grant-in-Aidfor Young
Scientists (B) 18750084 andScientific Research on Priority Areas
18032040 from the Ministry of Education, Culture, Sports, Science
andTechnology, Japan. M.S. acknowledges the Japan Society for the
Promotion of Science for a fellowship.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Scheme 1. Mechanism explaining the stereoselective formation of the
syn-configured a-allenol.
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Table 1: Rhodium-catalyzed syn-selective synthesis of a-allenols from alkynyl oxiranes using arylboronic
(Table 1, entry 12). Substrates 1e–
1g with five-, seven-, and eight-
membered-ring structures gave the
respective products 3ea–3ga ste-
acids.[a]
Entry Substrate 1
ArB(OH)2 2
Major product 3
Yield[%] [b] syn/anti[c]
reoselectively
in
high
yield
(Table 1, entries 13–15). In addi-
tion, the acyclic substrate 1h also
reacted with high yield and selec-
tivity (Table 1, entry 16). When
enantiomerically enriched 1a[18]
and 1i[19] were used, the enantio-
meric purity of the product 3aa and
3ia were exactly identical to those
of the starting oxiranes (Table 1,
entries 9 and 17).[20]
Next, we explored nucleophiles
other than arylboronic acids, and
found that MeMgCl reacted analo-
gously.[21] For example, treatment of
substrate 1j (1.0 equiv) with
MeMgCl (3.0 equiv) in the presence
of [{RhCl(nbd)}2] (5 mol% of Rh)
for 12 h at room temperature
afforded the desired methylated a-
allenol 3aa’ [Eq. (2); TMEDA =
N,N,N’,N’-tetramethylethylenedia-
mine]. However, the syn selectivity
was lower than that observed with
arylboronic acids.
In summary, we have developed
a rhodium-catalyzed reaction that
permits the construction of syn-
configured a-allenols from alkynyl
oxiranes and arylboronic acids.
Occurring with a high level of
diastereoselectivity under mild con-
ditions, the reaction will become a
good supplement to the well-stud-
ied copper-catalyzed reactions.
1
2
3
4
5
6
7
8
9
1a R=Me, R’=H
1a
1a
1a
1a
1a
1a
1a
2b Ar=4-FC6H4
2c Ar=4-BrC6H4
2d Ar=4-MeC6H4
2e Ar=3-MeOC6H4 3ae
2 f Ar=3-ClC6H4 3af
2g Ar=3-CHOC6H4 3ag
2h Ar=2-MeC6H4
2i Ar=2-thienyl
2a Ar=Ph
3ab
3ac
3ad
76
86
77
80
74
72
83
75
84
74
65
19
98:2
99:1
98:2
99:1
99:1
96:4
83:17
97:3
99:1
97:3
99:1
83:17
3ah
3ai
(R,R)-1a (82% ee)
(R,Sa)-3aa (82% ee)
10 1b R=C5H11, R’=H
11 1c R=C5H11, R’=Me
12 1d R=H, R’=H
2a Ar=Ph
2a Ar=Ph
2a Ar=Ph
3ba
3ca
3da
13
14
15
16
2a Ar=Ph
2a Ar=Ph
2a Ar=Ph
2a Ar=Ph
2a Ph
82
83
83
85
61
97:3
99:1
99:1
99:1
94:6
17
(S,S)-1i (80% ee)
(S,Ra)-3ia (80% ee)
[a] All reactions were carriedout using 1 (0.4 mmol), 2 (0.6 mmol), KOH (0.2–0.3 mmol), [{RhCl(nbd)}2]
(0.01 mmol, 5 mol% of Rh) in THF (4.0 mL) at RT for 3–16 h. [b] Yieldof isolatedproduct. [c] Relative
stereochemistry assignedby comparison with an authentic anti isomer preparedby the literature
procedure,[8g,9,11] andthe ratios were determinedby HPLC analysis of the isolatedmixture of the
allenols or the corresponding acetates.
a-
Experimental Section
Typical procedure: An oven-dried, Ar-
purged flask was charged with [{RhCl-
(nbd)}2] (4.3 mg, 9.3 mmol), 2a (68.0 mg, 0.56 mmol), KOH (13.0 mg,
0.23 mmol), THF (1.8 mL), and a solution of 1a (50.0 mg, 0.37 mmol)
in THF (1.8 mL). The reaction mixture was stirred at room temper-
ature for 2 h and quenched with water (10 mL). The aqueous layer
was extracted with ethyl acetate (3 ” 10 mL). The combined extracts
were washed with brine and dried over MgSO4. The solvent was
process of 1a worked well with an array of sterically and
electronically diverse arylboronic acids 2b–2h, as well as
heteroarylboronic acid 2i, to give syn-configured a-allenols
3ab–3ai with stereoselectivities higher than 96:4, except in
the case of the sterically hindered ortho-tolylboronic acid
(Table 1, entries 1–8).[17] It is worth pointing
out that the reaction conditions tolerate vari-
ous functional groups including a formyl group,
which is incompatible with Grignard reagents.
Substrate 1c, which has a tetrasubstituted
oxirane, also gave the tertiary alcohol 3ca
stereoselectively (Table 1, entry 11). The reac-
tion of substrate 1d having a terminal alkyne
moiety afforded the product 3da with a
decreased selectivity in only 19% yield
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Angewandte
Chemie
removed under reduced pressure and the residue was purified by
preparative thin-layer chromatography (hexane/ethyl acetate 5:1) to
give 3aa (63.6 mg, 81%, syn/anti = 99:1) as a pale yellow oil.
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[9] For a CuBr-catalyzed syn-selective reaction of 1a with alkyl
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a) A. Alexakis, I. Marek, P. Mangeney, J. F. Normant, Tetrahe-
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selective reaction of 1d with dialkylzinc reagents in the presence
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P. Crotti, F. Macchia, M. Pineschi, A. Arnold, B. L. Feringa,
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[10] J. Kjellgren, H. SundØn, K. J. Szabó, J. Am. Chem. Soc. 2005, 127,
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[11] M. Yoshida, H. Ueda, M. Ihara, Tetrahedron Lett. 2005, 46,
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Received: April 6, 2007
Revised: June 8, 2007
Published online: August 9, 2007
Keywords: b-oxygen elimination · addition · allenes · boron ·
.
rhodium
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