Iron-catalyzed synthesis of allenes from 2-alken-4-ynoates and grignard reagents

Article abstract of DOI:10.1002/adsc.201100995

Treatment of 2-alken-4-ynoates with methyl- or aryl-Grignard reagents and iron(II) chloride (10 mol%) afforded 5-methyl- or 5-aryl-3,4-alkadienoates in good yields as a single isomer after aqueous work-up. Likewise, (2-alken-4-ynoyl)oxazolidinones afforded (5-methyl-3,4-alkadienoyl) oxazolidinones. The aldol-type reaction with acetone was also possible in place of the hydrolytic work-up. Copyright

Full text of DOI:10.1002/adsc.201100995

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DOI: 10.1002/adsc.201100995
Iron-Catalyzed Synthesis of Allenes from 2-Alken-4-ynoates and
Grignard Reagents
Takeshi Hata,a Satoshi Iwata,a Shumpei Seto,a and Hirokazu Urabea,*
a
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of
Technology, 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan
Fax : (+81)-(0)45-924-5849; e-mail: hurabe@bio.titech.ac.jp
Received: December 22, 2011; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201100995.
Abstract: Treatment of 2-alken-4-ynoates with
methyl- or aryl-Grignard reagents and iron(II) chlo-
ride (10 mol%) afforded 5-methyl- or 5-aryl-3,4-al-
kadienoates in good yields as a single isomer after
aqueous work-up. Likewise, (2-alken-4-ynoyl)oxa-
zolidinones afforded (5-methyl-3,4-alkadienoyl)oxa-
zolidinones. The aldol-type reaction with acetone
was also possible in place of the hydrolytic work-
up.
Keywords: 1,6-addition; allenes; conjugated enynes;
Grignard reagents; iron
lated in 84% yield after aqueous work-up (Scheme 1).
Neither isomeric diene 4 nor acetylene 5 was detected
in the crude reaction mixture by careful 1H NMR
analysis. Deuteriolysis of the aforementioned reaction
mixture afforded mono-deuterated product 3-d with
high deuterium incorporation, showing the presence
Conjugate addition of Grignard reagents to a,b,g,d- of the enolate species 2[12] before work-up. This inter-
unsaturated carbonyl compounds is a useful method mediate 2 could be actually utilized in an aldol-type
to prepare unsaturated building blocks, provided that reaction with acetone to give homo-allenyl alcohol
both regioselectivity of the addition and stereoselec- 6.[13]
tivity of the remaining unsaturated bonds reach very
Recent reports claimed that some iron-catalyzed re-
high levels.[1] Recently, we achieved a 1,6-addition of actions might be actually catalyzed by copper impuri-
aryl-Grignard reagents to 2,4-alkadienoates and ties involved in the iron reagents.[14] The role of iron
-amides, satisfying these two requirements, by intro- as the actual catalyst in the present case is obvious
ducing an iron catalyst as shown in Eq. (1).[2,3] As part from the following findings (i)–(iii). (i) The similar re-
of our continuing study to broaden the application of action in the absence of the iron catalyst resulted in
this reaction to other a,b,g,d-unsaturated carbonyl the recovery of an intractable mixture of products. (ii)
compounds, we report here that Grignard reagents The use of FeCl2 of 99.998% purity[11] did not alter
undergo 1,6-addition to 2-alken-4-ynoates in the pres- the reaction course and gave virtually the same yield
ence of the same iron catalyst to give allenes[4] as for- and regio- and stereoselectivities of the 1,6-adduct.
mulated in Eq. (2). Although the similar 1,6-addition (iii) On the other hand, while copper catalysts
has been already performed with organocuprates de- (10 mol%) such as CuBr, CuBr·SMe2, CuI, CuCN,
rived from alkyllithiums,[5,6] alkyllithiums under CuCl2, and Li2CuCl4 furnished the desired product 3
copper catalysis,[7] and organoboranes or organotitani- in yields (0–65%) less than that in Scheme 1,[9] the
ums under Rh catalysis,[8] the present method is char- 1,6-addition no longer took place with 0.01 mol% of
acterized by the use of convenient Grignard reagents an effective catalyst (CuCl2[11,14b]), which is a 50 times
as the nucleophile.[9,10]
When tert-butyl 2-undecen-4-ynoate (1) was treated 99.998% pure FeCl2.
higher amount than that present as impurities in
with MeMgBr in the presence of a catalytic amount
A proposed mechanism of this reaction is shown in
of FeCl2 (10 mol%, 99.9% purity[11]), allene 3 was iso- Scheme 2. First, MeMgBr and a catalytic amount of
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Takeshi Hata et al.
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Scheme 1. Fe-catalyzed regioselective conjugate addition.
FeCl2 should generate methyliron intermediate such
Table 1 summarizes other results. The above reac-
as 7 (L=Me, Cl, or Br),[15] which plays a pivotal role tion is also applicable to aryl-Grignard reagents to
for the methyl transfer to the d-position to the car- give arylallenes, where relatively hindered aryl groups
bonyl group in 8, yielding 9.[12] Upon transmetallation such as those having an ortho-substituent gave prod-
with Grignard reagent, 9 generates the magnesium ucts in better yields (entries 2 and 3 vs. 4 and 5). This
enolate 2[12] and the initial organoiron reagent 7, presumably comes from the steric protection of the
which continues the catalytic cycle. At the final stage, allene portion against further nucleophilic addition
the resultant enolate 2 reacted with an electrophile (for an example, see ref.[19]) or the suppression of con-
again in a highly regioselective manner to give allene sumption of aryl-Grignard reagent via homocoupling
3 or 6 as the observed product.
process. The iron-regulated regioselectivity appears to
prevail over the steric hindrance at the reacting
carbon center, because sterically hindered t-Bu-substi-
tuted 2-penten-4-ynoate 12 still gave the expected
allene 19 exclusively in good yield (entry 6). Ethyl
ester 13, instead of 1 having a tert-butyl ester, sur-
vived the reaction conditions to give allenes 20 and 21
without any apparent decrease in the product yield
(entries 7 and 8). As a further extension of the sub-
strate scope, (2-alken-4-ynoyl)oxazolidinones 14a–
c (entries 9–11) were found to be suitable for this re-
action to give allenes 22a–c.[16,17] Optically active oxa-
zolidinones 14b and c showed moderate chiral induc-
tion in their products 22b and c (entries 10 and 11).
Ester and oxazolidinone groups in the products fa-
cilitate subsequent synthetic manipulation with the
allene portion remaining intact, as shown in
Scheme 3. While the reduction of ethyl or tert-butyl
esters 3 and 20 with LiAlH4 afforded the alcohol
24,[18] their conversion to 3,4-alkadienoic acid 25
under basic or acidic conditions, respectively, was un-
successful, only giving the corresponding 2,4-alkadi-
AHCTUNGTREGUNeNN noic acid. In this regard, oxazolidinone 22a was
found to be more promising, because its reduction to
alcohol 24 could be carried out with the milder LiBH4
and even its hydrolysis to carboxylic acid 25 was read-
Scheme 2. Proposed catalytic cycle. R=C6H13, X=O-t-Bu.
2
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Iron-Catalyzed Synthesis of Allenes from 2-Alken-4-ynoates and Grignard Reagents
Table 1. Preparation of the various allenes.
[a]
Diastereoselectivity was 67:33. The absolute stereochemistry of the allene part has not
been determined.
This reaction was performed at À788C for 3 h.
[b]
ily achieved,[16d] without any accompanying trace
amount of the isomeric 2,4-alkadienoic acid.
In contrast to 2-undecen-4-ynoate 13 shown in
Table 1, its isomeric 4-undecen-2-ynoate 23 [Eq. (3)]
or its amide derivative 26 [Eq. (4)] was not a good
substrate for this transformation to give a mixture of
complex products. However, under forcing conditions
involving the use of a stoichiometric amount of FeCl3
and excess methyl-Grignard reagent [Eq. (5)], the
latter amide 26 underwent an unusual double addition
of methyl groups to its acetylene bond to give dime-
thyldiene 27.[19] Despite its limited scope, the reaction
of Eq. (5) shows an interesting behavior of the orga-
noiron reagent toward carbon-carbon bond forma-
tion.
In conclusion, the highly selective remote addition
of Grignard reagents to a,b,g,d-unsaturated carbonyl
Scheme 3. Transformations of the products.
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compounds has been realized with the iron catalyst to
provide a new synthetic method for allenes.
Experimental Section
Typical Procedure for the Addition of Grignard
Reagent to Enynoates
To
a solution of tert-butyl (E)-2-undecen-4-ynoate (1)
(47.3 mg, 0.200 mmol) and FeCl2 (2.5 mg, 0.020 mmol, re-
agent of 99.9% purity purchased from Soekawa Chemicals
Co., Japan) in 1.0 mL of THF was added MeMgBr
(0.380 mL, 1.06M solution in THF, 0.400 mmol) at À788C
under argon. Then, the solution was slowly warmed to 08C
over 4.5 h. The reaction was terminated by the addition of
1M HCl solution (1.0 mL). The organic layer was separated
and the aqueous layer was extracted with ethyl acetate. The
combined organic layers were washed with aqueous saturat-
ed NaHCO3 solution and brine, dried over Na2SO4, and con-
1
centrated under vacuum to give a crude oil, H NMR analy-
sis of which did not show the presence of other regioisom-
ers. The crude product was chromatographed on silica gel
(hexane-ethyl acetate) to afford tert-butyl 5-methyl-3,4-un-
decadienoate (3) as an oil; yield: 42.3 mg (84%).
[4] Modern Allene Chemistry, Vols. 1 and 2, (Eds.; N.
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a) N. Krause, A. Hoffmann-Rçder, Tetrahedron 2004,
60, 11671–11694. For reviews on the preparation of al-
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or -ones, see: b) N. Krause, A. Gerold, Angew. Chem.
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g) S. Arndt, G. Handke, N. Krause, Chem. Ber. 1993,
Acknowledgements
This work was supported by JSPS, Japan through a Grant-in-
Aid for Scientific Research (B) (21350027) and a Grant-in-
Aid for Young Scientists (B) (23750102) to T. H.
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[19] A proposed mechanism of this reaction is shown in Eq.
(6), which involves (i) carbometallation of allene-substi-
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ligand exchange on the iron in 29 to generate 30, and
(iii) the extrusion of a lower-valent iron species FeLq to
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6 Iron-Catalyzed Synthesis of Allenes from 2-Alken-4-ynoates
and Grignard Reagents
Adv. Synth. Catal. 2012, 354, 1 – 6
Takeshi Hata, Satoshi Iwata, Shumpei Seto,
Hirokazu Urabe*
6
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