Iron-Catalyzed Cross-Coupling of Propargyl Ethers with Grignard Reagents for the Synthesis of Functionalized Allenes and Allenols

Article abstract of DOI:10.1002/anie.202106742

Herein we disclose an iron-catalyzed cross-coupling reaction of propargyl ethers with Grignard reagents. The reaction was demonstrated to be stereospecific and allows for a facile preparation of optically active allenes via efficient chirality transfer. Various tri- and tetrasubstituted fluoroalkyl allenes can be obtained in good to excellent yields. In addition, an iron-catalyzed cross-coupling of Grignard reagents with α-alkynyl oxetanes and tetrahydrofurans is disclosed herein, which constitutes a straightforward approach towards fully substituted β- or γ-allenols, respectively.

Full text of DOI:10.1002/anie.202106742

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Accepted Article
Title: Iron-Catalyzed Cross-Coupling of Propargyl Ethers with Grignard
Reagents for the Synthesis of Functionalized Allenes and
Allenols
Authors: Jan-E. Bäckvall, Daniels Posevins, and Aitor Bermejo-López
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Iron-Catalyzed Cross-Coupling of Propargyl Ethers with Grignard
Reagents for the Synthesis of Functionalized Allenes and Allenols
Daniels Posevins, Aitor Bermejo-López and Jan-E. Bäckvall*[a]
Dedication ((optional))
[a]
Dr. D. Posevins, A. Bermejo-López, Prof. Dr. J.-E. Bäckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University
Stockholm SE-10691 (Sweden)
E-mail: jeb@organ.su.se
Prof. Dr. J.-E. Bäckvall
Department of Natural Sciences, Mid Sweden University
SE-85170, Sundsvall (Sweden)
Supporting information and the ORCID identification number(s) for this article is given via a link at the end of the document.
Abstract: Herein we disclose an iron-catalyzed cross-coupling
reaction of propargyl ethers with Grignard reagents. The reaction was
demonstrated to be stereospecific and allows for a facile preparation
of optically active allenes via efficient chirality transfer. Various tri- and
tetrasubstituted fluoroalkyl allenes can be obtained in good to
excellent yields. In addition, an iron-catalyzed cross-coupling of
Grignard reagents with α-alkynyl oxetanes and tetrahydrofurans is
disclosed herein, which constitutes a straightforward approach
towards fully substituted β- or γ-allenols, respectively.
reactivity of the alkoxy group compared to conventional leaving
groups allows the presence of fluoroalkyl groups. The use of
cyclic analogues, α-alkynyl oxetanes and tetrahydrofurans as
substrates led to synthetically useful allenols.
Allenes constitute an interesting class of compounds and
have attracted considerable attention in synthetic organic
chemistry in recent years.[1] Functionalized allenes are frequently
used as building blocks in organic synthesis and they occur in a
range of natural products and pharmaceuticals.[2] An interesting
feature with functionalized allenes is that they can possess axial
chirality.
We[3-5] and others[6] have recently developed a large number
of diverse synthetic methods that rely on the use of various allene-
based starting materials. The development of new procedures for
the preparation of allenes is therefore highly desirable. A common
route towards functionalized allenes involves the copper- or iron-
catalyzed SN2’ reaction between Grignard reagents and
propargylic substrates.[7] Copper-catalyzed cross-couplings
between propargylic substrates and Grignard reagents are well
known but to date there are only few reports on the corresponding
iron-catalyzed cross-couplings and they mainly rely on the use of
sulfonates[8] or halides[9] as leaving groups. Fürstner have
reported a related method for the preparation of α-allenols that
utilizes alkynyl epoxide with its high ring strain as the nucleofuge
(Scheme 1a).[10] In addition, our group has recently disclosed a
practical method for the preparation of highly substituted
allenes[11a] and α-allenols[11b] via iron-catalyzed cross-coupling of
propargyl carboxylates and Grignard reagents (Scheme 1b). In
the present work we have studied iron-catalyzed cross-coupling
of less reactive propargylic ethers with Grignard reagents. With
methoxy as leaving group the stereospecificity (>99% syn-
displacement) is the highest ever reported in an iron-catalyzed
SN2’ substitution of propargylic substrates. Importantly, the low
Scheme 1. Syntheses of allenes and allenols via Fe-catalyzed cross-coupling
of Grignard reagents with propargylic substrates.
Our investigations began with the screening of various leaving
groups in the reaction of trifluoromethyl group-containing
propargylic substrates 1 in the presence of Fe(acac)3 as the
catalyst (Table 1). Unexpected formation of gem-difluoro 1,3-
enyne 3 was observed (60% yield) in the case of the acetate as
the leaving group (1aa) and only 20% yield of the desired
trifluoromethyl allene 2aa was obtained (entry 1, Table 1). For-
mation of 3 is thought to proceed via a propargyl radical interme-
diate.[12,13] Also, other oxygen-based leaving groups tested, such
as pivalate, carbonate, phosphonate, and mesylate provided the
desired allene 2aa in poor yields together with the 1,3-enyne 3 as
the main product (entries 2-5). These results demonstrate the
compatibility problems with fluoroalkyl group-containing
substrates in these attempted SN2’-type cross-coupling reactions.
1
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In a try to circumvent this problem we tested methoxy as the
leaving group. Interestingly, this leaving group suppressed the
undesired formation of the elimination product 3, and the allene
product 2aa was now obtained in 94% yield with no detectable
amounts of the side product 3 (entry 6).[14] FeCl3 as the catalyst
showed similar performance as that of Fe(acac)3 in this reaction,
albeit providing the desired allene in a slightly decreased 92%
yield (entry 7). Fe(OAc)2 as the catalyst failed to give the desired
product in this transformation (entry 8). Screening of some
commonly used additives did not lead to any increase in yield of
allene 2aa (entries 9 and 10). The use of CuBr as the catalyst in
place of Fe(acac)3 did not lead to any detectable amounts of the
desired product 2aa (entry 11). This observation not only shows
that iron is superior to copper as the catalyst in this reaction but
also rules out that the reaction is catalyzed by trace amounts of
copper in the commercially available Fe(acac)3.[14]
TBS-protected CF3 and CHF2 group-containing α-allenols 2e and
2f were prepared in 85% and 77% yields, respectively, using the
newly developed methodology (entry 7). The β-enallenes 2g and
2h were obtained from the corresponding 1g and 1h in 88% and
75% yields, respectively (entries 8 and 9). The cross-coupling
reaction with substrate 1i afforded allene product 2i without any
formation of cyclopentyl moiety-containing product(s) that would
be expected from cyclization of an intermediate propargyl radical
species (entry 9). Furthermore, cyclopropyl-substituted propargyl
methyl ether 1j as the substrate gave 2j in 56% yield, and,
interestingly, did not result in any side products arising from the
radical ring-opening of the cyclopropane ring (entry 10). The use
of propargyl methyl ether 1k gave the desired allene 2k in a low
17% yield, possibly due to an unfavorable coordination of the
pyridine moiety to the metal center (entry 11).
The use of 1 equiv. of TEMPO as an additive in the reaction
of 1af with PhMgBr did not completely shut down the reaction, but
afforded the desired allene product 2ac in 34% yield (see the
Supporting Information). These results strongly suggest, that
carbon-centered radical intermediates are either extremely short-
lived or are not involved in the reaction process.
Table 1. Optimization of the reaction conditions.[a]
Table 2. Preparation of fluoroalkyl allenes 2.[a]
Yield
2aa [%][b]
of
Yield of
3 [%][b]
Entry
Substrate (1)
Catalyst
[
]
c
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
1
2
3
1aa (R=Ac)
20
15
19
60
58
69
1ab (R=Piv)
1ac (R=CO2Me)
Yield of 2
[%][b]
Entry
1
Substrate (1)
R4MgX
Product (2)
1ad
(R=P(O)(OEt)2)
4
25
67
Fe(acac)3
Fe(acac)3
FeCl3
5
1ae (R=Ms)
18
47
MeMgBr
89
6
1af (R=Me)
94 (89)
92
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
7
1af
1af
1af
1af
1af
n-
[d]
Fe(OAc)2
Fe(acac)3
Fe(acac)3
CuBr
2
3
4
5
6
7
8
43[c]
62[d]
74
8
-
BuMgCl
9[e]
10[f]
11
92
91
[g]
-
PhMgBr
MeMgBr
MeMgBr
MeMgBr
MeMgBr
MeMgBr
[a]Reaction conditions: 0.2 M solution of propargylic substrate 1 (0.3 mmol) in
PhMe, catalyst (5 mol%) with dropwise addition of Grignard reagent.
[b]Determined by NMR using anisole as the internal standard. Isolated yield in
parentheses. [c]≥99.9%. [d]1af was recovered in 93% yield. [e]Using 20 mol% of
TMEDA as an additive. [f]Using 20 mol% of IMes•HCl as an additive. [g]1af was
recovered in 96% yield. acac
tetramethylethylenediamine.
= acetylacetonate. TMEDA = N,N,N,N-
92
With the optimized reaction conditions in hand, we further
studied the reactivity of various fluorinated propargyl methyl
ethers 1 (R3 = fluoroalkyl) in this transformation (Table 2). The use
of other Grignard reagents such as n-BuMgCl and PhMgBr in the
reaction with 1af afforded the corresponding trifluoromethyl
allenes 2ab and 2ac in 43% and 62% yields, respectively (entries
2 and 3, Table 2). The observed lower yield of product 2ab is most
likely due to competing β-hydride elimination in the alkyliron
intermediate initially formed from Fe(acac)3 and the Grignard
reagent. Allenes 2b and 2c, containing masked alcohol and
aldehyde functionalities, respectively, were prepared in good to
high yields from the corresponding substrates 1b and 1c (entries
4 and 5). Pentafluoroethyl group-containing substrate 1d afforded
the corresponding allene 2d in 72% yield (entry 6). Interestingly,
72
2e: 85
2f: 77
88
2
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2h: 75
2i: 78
5d: 85
5e: 56[c]
9
MeMgBr
MeMgBr
PhMgBr
3
4
5
6
7
8
MeMgBr
BnMgCl
MeMgBr
PhMgBr
MeMgBr
MeMgBr
10
11
56
71
68
17[e]
4f
[a]Reaction conditions: 0.2 M solution of propargyl methyl ether 1 (0.3 mmol) in
PhMe, Fe(acac)3 (5 mol%) with dropwise addition of Grignard reagent (1.5
equiv). [b]Isolated yield. [c]Using 10 mol% of TMEDA as an additive. [d]2.0 equiv.
of PhMgBr was used and the reaction time was 4h. [e]The reaction time was 12h
and 1k was recovered in 43% yield.
65[d]
We were delighted to find that the use of cyclic ether 4a as
the substrate in the reaction led to formation of the CF3 group-
containing γ-allenol 5a in an excellent 88% yield (eq. 1). γ-Allenols
are highly desired substrates for many transition metal-catalyzed
transformations as well as important building blocks in the total
synthesis of natural products.[15] The examples of preparation of
γ-allenols currently found in the literature typically involve
multistep syntheses.
67
55
[a]Reaction conditions: 0.2 M solution of tetrahydrofuran 4 (0.3 mmol) in PhMe,
Fe(acac)3 (5 mol%) with dropwise addition of Grignard reagent (1.5 equiv).
[b]Isolated yield. [c]2.5 equiv. of MeMgBr was used. [d]2.0 equiv. of PhMgBr was
used and the reaction time was 1h.
To the best of our knowledge, the use of α-alkynyl oxetanes
as substrates has not previously been explored in the Fe-cata-
lyzed cross coupling with Grignard reagents. Herein we disclose
a simple and practical method for accessing synthetically useful
β-allenols from the readily available α-alkynyl oxetanes 6 as
substrates (Scheme 2 and Table S1). β-Allenols 7a and 7b were
obtained in 78% and 81% yields, respectively under the standard
reaction conditions via the cross-coupling of 6a and 6b with the
corresponding Grignard reagents. The use of β-hydrogen-
containing Grignard reagents such as EtMgBr and CyMgBr in the
transformations of oxetanes 6c and 6d allowed for the preparation
of the corresponding products 7c and 7d in 56% and 71% yields,
respectively. Trisubstituted β-allenol 7e was obtained in 57% yield
under the standard conditions from the reaction of 6e with
MeMgBr (entry 5).
Because of the demand of new efficient methods for the
preparation of functionalized allenols we decided to investigate
additional α-alkynyl tetrahydrofurans 4 as substrates in this
reaction (Table 3). Tetrahydrofurans 4b-4e containing alkyl
substituents in the R1 and R2 positions afforded the corresponding
γ-allenols 5b-5e in 56-85% yields under the standard reaction
conditions (entries 2 and 3, Table 3). Interestingly, the reaction
tolerates the presence of a free hydroxyl group in substrate 4e
and afforded the diol product 5e in a moderate 56% yield. α-
Alkynyl tetrahydrofuran 4f, containing a hydrogen atom in the R2
position, gave the desired trisubstituted γ-allenols 5fa and 5fb in
good yields (entries 4 and 5). Substrates 4g and 4h bearing an
aryl group in the R2 position furnished the corresponding products
5g and 5h in 65% and 67% yields, respectively (entries 6 and 7).
Trisubstituted γ-allenol 5i was prepared by cross-coupling of 4i
with MeMgBr under the standard reaction conditions in a
moderate 55% yield (entry 8).
Table 3. Preparation of γ-allenols 5.[a]
Scheme 2. Preparation of β-allenols 7. Reaction conditions: 0.2 M solution of
oxetane 6 (0.3 mmol) in PhMe, Fe(acac)3 (5 mol%) with dropwise addition of
Grignard reagent (1.5 equiv). [a] Using 10 mol% of TMEDA as an additive.
Yield of 5
[%][b]
Entry
1
Substrate (4)
R3MgX
Product (5)
To demonstrate the scalability of the herein described iron-
catalyzed synthesis of fluoroalkyl allenes we performed the
transformation of propargyl ether 1e on a gram-scale (Scheme
3a). The desired trifluoromethyl allene 2e was obtained in an
excellent 88% yield. To show-case the potential synthetic utility of
the obtained fluoroalkyl allenes, 2h was subjected to the regio-
and stereoselective palladium-catalyzed oxidative borylation
MeMgBr
88
5b: 73
5c: 68
2
BnMgCl
3
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reaction[16] to give the trifluoromethyl group-containing borylated
triene product 8 in 67% yield (Scheme 3b).
We also investigated the stereochemistry of the iron-
catalyzed Grignard reaction (Scheme 3c). Enantiomerically
enriched substrates 1l-n were conveniently prepared via an
enzymatic kinetic resolution of the corresponding secondary
propargyl alcohols, followed by methylation using methyl iodide
(see the Supporting Information). Interestingly, products 2l-n
were formed under the standard reaction conditions with excellent
transfer of chirality from the corresponding propargyl ethers 1l-n
in good yields. Propargylic substrate (R)-1l gave the allene
product (R)-2l. The structure and absolute configuration of (R)-2l
was established by X-ray crystallography of its ester derivative
(R)-9 (DNB = 2,5-dinitrobenzoyl). These results show that a syn-
SN2’ displacement of the methoxy group by the aryl group has
occurred, which, in line with the radical probe experiments, rules
out the involvement of carbon-based radical species generated
from the substrate (R)-1l.
Scheme 4. Preparation of non-fluorinated allenes 2o-2s. Reaction conditions:
0.2 M solution of methyl ether 1 (0.3 mmol) in PhMe, Fe(acac)3 (5 mol%) with
dropwise addition of Grignard reagent (1.5 equiv).
plex.[17,18] Based on the observed transfer of chirality, the reaction
is proposed to proceed via a syn-SN2’ attack of the initially
generated organoiron intermediate on substrate 1 (oxidative
addition) to generate Int-B via Int-A (Scheme 5). Reductive
elimination from Int-B would give trisubstituted allene product 2
with the observed axial chirality.
Scheme 5. Proposed reaction mechanism.
In conclusion, we have developed a facile method for cross-
coupling of propargyl ethers with Grignard reagents that involves
the use of a nontoxic and commercially available iron catalyst.
Interestingly, the method allows for the preparation of highly sub-
stituted fluoroalkyl allenes as well as for the preparation of β- and
γ-allenols (from readily available α-alkynyl cyclic ethers). The
preparation of fluoroalkyl allenes was scalable up to gram-scale
and the use of enantiomerically enriched starting materials led to
formation of the desired chiral allenes via a syn-SN2’ process with
excellent transfer of chirality. To the best of our knowledge this is
the highest stereospecificity ever reported in an iron-catalyzed
SN2’ substitution reaction of propargylic substrates.[19] Hence, the
newly developed transformation constitutes a synthetically useful
method for the preparation of chiral allenes.[11a,20,21] The results
obtained by using radical probes together with the observed
transfer of chirality from the substrate to product rules out a radical
pathway in the oxidative addition (1 → Int-B, Scheme 5). More in-
depth investigations of the reaction mechanism and further
applications of the obtained products are currently underway in
our laboratory.
Scheme 3. Additional experiments.
We also investigated the preparation non-fluorinated allenes
2o-2s using propargyl methyl ethers 1o-1s as substrates under
the standard reaction conditions (Scheme 4). Substrates 1o-1p
bearing alkyl substituents in R1, R2 and R3 positions all afforded
the corresponding tetrasubstituted allene products 2o-2p in good
yields with high selectivity. Trisubstituted allene 2q was prepared
in 92% yield by reacting TMS group-containing Grignard reagent
with propargyl methyl ether 1q. Cross-coupling of ester group-
containing substrates 1r and 1s with MeMgBr afforded allenes 2r
and 2s in 51% and 73% yields, respectively.
Acknowledgements
The Swedish Research Council (2019-04042), the Olle Engkvist
Foundation, the Knut and Alice Wallenberg Foundation (KAW
2016.0072), the Swedish Foundation for Strategic Environmental
Research (Mistra: project Mistra SafeChem, project number
2018/11), and the European Union are gratefully acknowledged
for the financial support.
In the iron-catalyzed coupling reaction it is thought that the
Grignard reagent initially reacts with the iron catalyst Fe(acac)3 to
generate a reduced organoiron complex, probably an “ate” com-
4
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[15] a) X. Xie, S. Ma, Chem. Commun. 2013, 49, 5693; b) B. Alcaide, P.
Almendros, T. Martínez del Campo, E. Soriano, J. Marco‐Contelles,
Chem. Eur. J. 2009, 15, 1909.
Keywords: Iron catalysis • cross-coupling • Grignard reagents •
fluoroalkyl allenes
[16] Y. Qiu, B. Yang, C. Zhu, J.-E. Bäckvall, Angew. Chem. Int. Ed. 2016, 55,
6520; Angew. Chem. 2016, 128, 6630;
[1]
a) S. Ma, Chem. Rev. 2005, 105, 2829; b) C. Aubert, L. Fensterbank, P.
Garcia, M. Malacria and A. Simonneau, Chem. Rev. 2011, 111, 1954; c)
N. Krause and C. Winter, Chem. Rev. 2011, 111, 1994; d) N. Krause and
A. S. K. Hashmi, “Modern Allene Chemistry” Wiley-VCH, Weinheim,
2004. e) X. Huang and S. Ma, Acc. Chem. Res. 2019, 52, 1301; f) J. M.
Alonso and P. Almendros, Chem. Rev. 2021, 121, 4193.
a) A. Hoffmann‐Röder and N. Krause, Angew. Chem. Int. Ed. 2004, 43,
1196; Angew. Chem. 2004, 116, 1216; b) S. Yu and S. Ma, Angew. Chem.
Int. Ed. 2012, 51, 3074; Angew. Chem. 2012, 124, 3128.
a) B. Yang, Y. Qiu, and J.-E. Bäckvall, Acc. Chem. Res. 2018, 51, 1520;
b) C. Zhu, B. Yang, B. Khanh Mai, S. Palazzotto, Y. Qiu, A.
Gudmundsson, A. Ricke, F. Himo, and J.-E. Bäckvall, J. Am. Chem. Soc.
2018, 140, 14324; c) M.-B. Li, A. K. Inge, D. Posevins, K. P. J. Gustafson,
Y. Qiu, and J.-E. Bäckvall, J. Am. Chem. Soc. 2018, 140, 14604; d) J.
Liu, A. Ricke, B. Yang and J.-E. Bäckvall, Angew. Chem. Int. Ed. 2018,
57, 16842; Angew. Chem. 2018, 130, 17084. e) M.-B. Li, D. Posevins, A.
Geoffroy, C. Zhu, and J.-E. Bäckvall, Angew. Chem. Int. Ed. 2020, 59,
1992; Angew. Chem. 2020, 132, 2008; (f) M.-B. Li, Y. Yang, A. A. Rafi,
M. Oschmann, E. Svensson Grape, A. K. Inge, A. Córdova, and J.-E.
Bäckvall, Angew. Chem. Int. Ed. 2020, 59, 10391; Angew. Chem. 2020,
132, 10477.
[17] S. Sandl, A. Jacobi von Wangelin, Angew. Chem. Int. Ed. 2020, 59, 5434;
Angew. Chem. 2020, 132, 5474.
[18] a) J. D. Sears, S. B. MuÇoz, S. L. Daifuku, A. A. Shaps, S. H. Carpenter,
W.W. Brennessel, M. L. Neidig, Angew. Chem. Int. Ed. 2019, 58, 2769;
Angew. Chem. 2019, 131, 2795; b) R. B. Bedford, Acc. Chem. Res. 2015,
48, 1485; c) A. Fürstner, R. Martin, H. Krause, G. Seidel, R. Goddard, C.
W. Lehmann, J. Am. Chem. Soc. 2008, 130, 8773.
[2]
[3]
[19] The stereospecificity with methoxy as the leaving group, >99% syn-
displacement, is the highest ever reported for iron-catalyzed substitution
of propargylic substrates. In ref. [10] and [11] the stereospecificity is
much lower; In ref. [10] it is at best 92% syn / 8% anti and in ref. [11] the
reaction proceeded predominantly anti at low temp (-78 oC) but 76% syn
/ 24% anti at 0 oC.
[20] For recent reviews on catalytic asymmetric syntheses of allenes see: a)
J. Ye, S. Ma, Org. Chem. Front., 2014, 1, 1210; b) R. K. Neff, D. E. Frantz,
ACS Catal., 2014, 4, 519; c) W. -D. Chu, Y. Zhang, J. Wang, Catal. Sci.
Technol., 2017, 7, 4570.
[21] For enantioselective synthesis of allenylboronates see: a) H. Ito, Y.
Sasaki, M. Sawamura, J. Am. Chem. Soc. 2008, 130, 15774; b) D.-W.
Gao, Y. Xiao, M. Liu, Z. Liu, M. K. Karunananda, J. S. Chen, K. M. Engle,
ACS Catal. 2018, 8, 3650; c) H. L. Sang, S. Yu, S. Ge, Org. Chem. Front.
2018, 5, 1284; d) Y. Huang, J. del Pozo, S. Torker, A. H. Hoveyda J. Am.
Chem. Soc. 2018, 140, 2643.
[4]
[5]
B. Yang, C. Zhu, Y. Qiu, J.-E. Bꢀckvall, Angew. Chem., Int. Ed. 2016, 55,
5568; Angew. Chem. 2016, 128, 5658.
a) A. Guðmundsson, K. P. J. Gustafson, B. K. Mai, B. Yang, F. Himo, J.-
E. Bꢀckvall, ACS Catalysis 2018, 8, 12; b) A. Guðmundsson, K. P. J.
Gustafson, B. K. Mai, B. Yang, F. Himo, J.-E. Bäckvall, ACS Catal. 2019,
9, 1733.
[6]
[7]
a) A. S. K. Hashmi, Angew. Chem. Int. Ed. 2000, 39, 3590; Angew. Chem.
2000, 112, 3737; b) S. Ma, Acc. Chem. Res. 2003, 36, 701; c) K.
Brummond, J. DeForrest, Synthesis 2007, 795; d) S. Yu, S. Ma, Chem.
Commun. 2011, 47, 5384; e) S. Kitagaki, F. Inagaki, C. Mukai, Chem.
Soc. Rev. 2014, 43, 2956; f) L. Liu, R. M. Ward, J. M. Schomaker, Chem.
Rev. 2019, 119, 12422; g) X. Huang, S. Ma, Acc. Chem. Res. 2019, 52,
1301.
a) D. J. Burton, G. A. Hartgraves, J. Fluorine Chem. 2009, 130, 254; (b)
T. S. N. Zhao, K. J. Szabꢁ, Org. Lett. 2012, 14, 3966; (c) X. Jiang, F.-L.
Qing, Beilstein J. Org. Chem. 2013, 9, 2862; (d) Y. Miyake, S. -I. Ota, M.
Shibata, K. Nakajima, Y. Nishibayashi, Chem. Commun. 2013, 49, 7809;
(e) Y.-L. Ji, J.-J. Kong, J.-H. Lin, J.-C., Xiao, Y.-C. Gu, Org. Biomol. Chem.
2014, 12, 2903; (f) G. Li, P. D. Gagare, P. V. Ramachandran,
Tetrahedron Lett. 2014, 55, 5736; (g) B. R. Ambler, S. Peddi, R. A.
Altman, Synthesis 2014, 46, 1938; (h) B. R. Ambler, S. Peddi, R. A.
Altman, Org. Lett. 2015, 17, 2506; (i) Y.-L. Ji, J.-J. Luo, J.-H. Lin, J.-C.
Xiao, Y.-C. Gu, Org. Lett. 2016, 18, 1000.
[8]
[9]
A.S.K. Hashmi, G. Szeimies, Chem. Ber., 1994, 127, 1075.
a) D. J. Pasto, G. F. Hennion, R. H. Shults, A. Waterhouse, S. -K. Chou,
J. Org. Chem. 1976, 41, 3496; b) D. J. Pasto, S. -K. Chou, A. Waterhouse,
R. H. Shults, G. F. Hennion, J. Org. Chem. 1978, 43, 1385; c) P.
Domingo‐Legarda, R. Soler‐Yanes, M. T. Quirós‐López, E. Buñuel, D. J.
Cárdenas, Eur. J. Org. Chem., 2018, 4900; d) I. Manjón-Mata, M. T.
Quirós, E. Buñuel, D. J. Cárdenas, Adv. Synth. Catal. 2020, 362, 146.
[10] A. Fürstner, M. Mendez, Angew. Chem. Int. Ed. 2003, 42, 5355; Angew.
Chem. 2003, 115, 5513.
[11] a) S. N. Kessler, J.-E. Bäckvall, Angew. Chem. Int. Ed. 2016, 55, 3734;
Angew. Chem. 2016, 128, 3798; b) S. N. Kessler, F. Hundemer, J.-E.
Bäckvall, ACS Catal. 2016, 6, 7448.
[12] The proposed mechanism for formation of product 3 involves the
formation of a propargyl radical, followed by further reduction by Fe or
Mg species and β-fluoride elimination:
[13] For a related C-F bond cleavage see: H. Amii, T. Kobayashi, Y. Hatamoto,
K. Uneyama, Chem. Commun., 1999, 1323.
[14] The Fe(acac)3 obtained from Sigma-Aldrich had a copper content of 0.5
ppm.
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10.1002/anie.202106742
Angewandte Chemie International Edition
COMMUNICATION
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A method for facile synthesis of highly substituted allenols and fluoroalkyl allenes via iron-catalyzed cross-coupling reaction of propargyl
ethers with Grignard reagents is disclosed. Various tri- and tetrasubstituted fluoroalkyl allenes and β-/γ-allenols were obtained in good
to excellent yields. The reaction was demonstrated to be stereospecific occurring with syn-SN2’ displacement of the methoxy group by
the Grignard reagent.
Institute and/or researcher Twitter usernames: @BackvallJEB_grp
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This article is protected by copyright. All rights reserved.