Asymmetric Synthesis of Fluorinated Allenes by Rhodium-Catalyzed Enantioselective Alkylation/Defluorination of Propargyl Difluorides with Alkylzincs

Article abstract of DOI:10.1002/anie.202109290

The reaction of propargyl difluorides R¹CF₂C≡CR² with alkylzincs R³ZnCl giving axially chiral fluorinated allenes R¹FC=C=CR²R³ with high enantioselectivity (up to 99 % ee) was found to be catalyzed by a chiral diene/rhodium complex. A key step in the catalytic cycle is selective elimination of one of the enantiotopic fluorides at the β-position of an alkenyl-Rh intermediate, which is generated by regioselective addition of R³-Rh onto the triple bond of the starting difluorides.

Full text of DOI:10.1002/anie.202109290

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Asymmetric Synthesis of Fluorinated Allenes by Rhodium-
Catalyzed Enantioselective Alkylation/Defluorination of Propargyl
Difluorides with Alkylzincs
Authors: Jia Sheng Ng and Tamio Hayashi
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10.1002/anie.202109290
Angewandte Chemie International Edition
COMMUNICATION
Asymmetric Synthesis of Fluorinated Allenes by Rhodium-
Catalyzed Enantioselective Alkylation/Defluorination of Propargyl
Difluorides with Alkylzincs
Jia Sheng Ng[b] and Tamio Hayashi*[a,b]
Abstract: The reaction of propargyl difluorides R1CF2C≡CR2 with
alkylzincs R3ZnCl giving axially chiral fluorinated allenes
a) Asymmetric arylation/defluorination of trifluoromethylalkenes:
Hayashi (2016), Lautens (2018)
[Rh]
R1FC=C=CR2R3 with high enantioselectivity (up to 99% ee) was
found to be catalyzed by a chiral diene/rhodium complex. A key step
in the catalytic cycle is selective elimination of one of the
enantiotopic fluorides at -position of an alkenyl–Rh intermediate
which is generated by regioselective addition of R3–Rh onto the
triple bond of the starting difluorides.
F
R
*
Rh/L* (catalyst)
F
F
R
F
F
R
*
+ ArB(OH)2
F
Ar
F
Ar
F
F–[Rh]
b-
F elimination
b) Asymmetric alkylation/defluorination of 1-(difluoroalkyl)alkynes giving axially
chiral fluoroallenes: this work
R1
R1
F
Rh/L* (catalyst)
R3
R2
Axially chiral allenes have attracted increasing attention owing to
their synthetic utility based on their unique structure and
reactivity.[1] While a variety of catalytic asymmetric reactions
have been reported for obtaining axially chiral allenes,[1,2] it is still
important and challenging to develop a new efficient method of
synthesizing this class of chiral molecules with high
enantioselectivity. Here we report rhodium-catalyzed asymmetric
synthesis of tetra-substituted chiral allenes[3] where one of the
four substituents is fluoride.[4,5]
+ R3–ZnCl
R2
•
up to 99% ee
F
F
F
R3–ZnCl
F
[Rh] R3
R2
2
R1
A
1
transmetalation
carborhodation
F
[Rh]
F
R1
R3
R2
[Rh]
F
R1
R3
•
enantioselective
F elimination
C
R2
F
b-
3
B
We have previously reported that the reaction of 1-
trifluoromethylalkenes with arylboronic acids in the presence of a
c) Asymmetric synthesis of chloroallenes by Cu-catalyzed alkyation
of progargyl dichlorides: Alexakis (2012)
chiral
diene/Rh
catalyst
gives
enantioenriched
1,1-
difluoroalkenes[6] (Scheme 1a). This reaction is different from
other Rh-catalyzed asymmetric arylation reactions[7] in that its
catalytic cycle involves -fluoride elimination[8,9,10] from an alkyl–
H
H
Cu/L* (catalyst)
R2
R1
+ R2MgBr
R1
•
Cl
Cl
Cl
Scheme 1. Catalytic asymmetric synthesis of axially chiral allenes by rhodium-
catalyzed alkylation/defluorination.
Rh intermediate generated by the arylrhodation of
a 1-
trifluoromethylalkene. More recently this type of asymmetric
reactions that produce 1,1-difluoroalkenes bearing a chiral
carbon center at the allylic position have been developed for the
synthesis of enantioenriched allyl-boranes and -silanes.[11] Here
we report asymmetric synthesis of fluoride-substituted chiral
allenes (Scheme 1b), where the stereochemical outcome is
decided at -elimination of one of the two enantiotopic fluorides
from the alkenyl-Rh intermediate B. As a catalytic asymmetric
reaction related to ours in terms of reaction pathway, Alexakis
has previously reported copper-catalyzed asymmetric reaction of
propargyl dichlorides with alkyl Grignard reagents giving
chloride-substituted allenes[12] (Scheme 1c). There have been
two reports on the asymmetric synthesis of chiral fluoroallenes.
One is asymmetric reduction of trifluoroallene with a chiral
zirconocene hydride giving 1,3-difluoroallene reported by
Lentz[4a] and the other is Rh(III)-catalyzed C-H activation
reported by Wang during his studies on asymmetric synthesis of
isoindolinones.[4b]
Scheme 2 shows some of the results obtained for our
preliminary experiments using a rhodium/1,5-cyclooctadiene
(cod) catalyst to find the conditions where the target product,
fluoride-substituted allene, is formed in a high yield with high
chemoselectivity. The reaction of propargyl difluoride 1a with
PhB(OH)2 (2a) under the conditions used for the reaction of
trifluoromethylalkenes[6] (Scheme 1a), that is, with KOH (20
mol%) in dioxane/H2O (10/1) at 50 °C, gave 22% yield of the
fluoroallene 3aa, together with 15% of hydrophenylation product
4 and 37% of ortho-disubstituted benzene 5. The side products 4
and 5 are most likely formed through the intermediate D which is
generated from intermediate B by 1,4-shift of rhodium from
alkenyl carbon to ortho-position of the phenyl ring.[13] Although
the formation of 5 with this good selectivity is interesting in its
reaction pathway as well as in the synthetic utility of 5, we focus
our present study on the synthesis of fluoroallenes in a high
yield. Use of zinc reagent PhZnCl (2a’)[14,15] instead of PhB(OH)2
(2a) improved the yield of allene 3aa (66%), but the reaction was
still accompanied by the formation of 5 albeit in a lower yield
(31%). It turned out that organozinc nucleophiles which do not
undergo the 1,4-shift produce the corresponding fluoroallenes in
high yields. Thus, 3,5-dichlorophenylzinc chloride (2b), where
the Cl-substituents at meta-positions prohibit the rhodium from
shifting to the ortho-positions, gave high yield (90%) of the
fluoroallene 3ab with high selectivity. Interestingly, benzylzinc
chloride (2c), which has been rarely used for rhodium-catalyzed
[a] Prof. Dr. T. Hayashi
Department of Chemistry, National Tsing-Hua University
Hsinchu 30013, Taiwan
E-mail: hayashi@mx.nthu.edu.tw
[b] J. S. Ng, Prof. Dr. T. Hayashi
Division of Chemistry and Biological Chemistry
School of Physical and Mathematical Sciences
Nanyang Technological University
21 Nanyang Link, Singapore 637371 (Singapore)
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.202109290
Angewandte Chemie International Edition
COMMUNICATION
addition reactions onto either alkynes or alkenes,[7] was found to
be an active reagent for the present reaction to give the
corresponding allene 3ac in 90% yield.
Entry Variations from standard
conditions (shown above)
Conv (%)[b] Yield (%)[c] % ee[d] of
of 1a
of 3ad
3ad
1
2
3
4
none
96
98
94
92
75
74
61
60
98 (S)
92 (R)
96 (R)
97 (R)
tBu
H
Hex
[RhCl(L1*)]2
[RhCl(L2*)]2
[RhCl(L3*)]2
F
F
F
•
tBu
F
Ph
a) or b)
Ph
•
F
F
F
+
Hex
+
Hex
tBu Hex
tBu
F
1a
tBu Hex
3aa
5
4
a) 1a + PhB(OH)2 (2a)
b) 1a + PhZnCl (2a')
22%
66%
15%
3%
37% yieldc)
31% yieldc)
5
6
7
8
[RhCl(L4*)]2
72
0
69
0
91 (R)
—
[RhCl(coe)2]2 + (R)-binap[e]
[RhCl(coe)2]2 + (R)-segphos[f]
0 °C instead of 25 °C
[Rh]
[Rh]
H2O
0
0
—
4
5
1a
F
F
Ph
[Rh] Ph
F
F
1,4-shift
Cl
25
21
98 (S)
tBu Hex
A
1a
tBu Hex
B
D
9
50 °C instead of 25 °C
97
71
78
55
96 (S)
90 (R)
Cl
+
10 [RhCl(L4*)]2 and ZnBr2 (2.4 equiv)
tBu
b)
b)
1a
1a
ZnCl
•
Cl
Hex
11 [RhCl(L4*)]2 and ZnCl2 (3.0 equiv)
12 [RhCl(L4*)]2 and ZnCl2 (5.0 equiv)
60
43
47
24
90 (R)
91 (R)
90% yieldd)
90% yieldd)
F
2b
3ab
Cl
Ph
tBu
+ PhCH2ZnCl
•
Hex
F
[a] Reaction conditions: Alkyne 1a (0.15 mmol), ArCH2ZnCl 2d (0.30 mmol),
ZnCl2 (0.36 mmol), and Rh catalyst (5 mol% of Rh) in THF (0.8 mL) at 25 °C
for 14 h. The zinc reagent ArCH2ZnCl was generated by the reaction of
ArCH2MgBr (1.0 equiv) with ZnCl2 (2.2 equiv) in THF. For the details, see
Supporting Information. [b] Determined by 19F NMR of the crude reaction
mixture. [c] Isolated yield. [d] The % ee was determined by HPLC on a chiral
2c
3ac
a) PhB(OH)2 (2 equiv), [RhCl(cod)]2 (5 mol% Rh), KOH (20 mol%), dioxane/H2O
(10/1) at 50 °C for 14 h. b) RZnCl (2 equiv), [RhCl(cod)]2 (5 mol% Rh), THF at 25
°C for 14 h, and then H2O. c) Yields by NMR analysis. d) Isolated yields.
Scheme 2. Rhodium-catalyzed reaction of propargyl difluoride 1a with
organoboron and zinc reagents producing fluorinated allenes 3.
stationary phase column. [e] binap
= 2.2’-bis(diphenylphosphino)-1,1’-
binaphthyl. [f] segphos = 5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole.
The reaction of propargyl difluoride 1a with 3-
methoxybenzylzinc chloride (2d) (2.0 equiv)[16] was examined
using several chiral diene ligands[17] for the high chemo- and
enantio-selectivity in giving chiral allene 3ad (Table 1). The best
result was obtained with a rhodium/Fc-tfb catalyst[18] (5 mol%
Rh) in the presence of 2.4 equiv of ZnCl2 in THF at 25 °C for 14
h, which gave 75% yield of (S)-3ad with 98% ee (entry 1). Other
chiral diene/rhodium complexes[19] also catalyzed the reaction to
give 60–74% yields of 3ad, while the enantioselectivity was
lower to some extent (entries 2–5). Bisphosphine/rhodium
complexes are not catalytically active for the present reaction,
leaving the propargyl difluoride 1a unreacted (entries 6 and 7).
The reaction was very slow at 0 °C and the enantioselectivity
was lower at 50 °C (entries 8 and 9). The effects of the zinc salts
on the present asymmetric reaction were studied in the reaction
with amide ligand L4* (entries 5 vs 10–12). The use of ZnBr2
instead of ZnCl2 gave the product 3ad with essentially the same
enantioselectivity (90% ee) albeit in a lower yield. The amount of
ZnCl2 did not affect the enantioselectivity, the % ee being kept
between 90% and 91% with 3 and 5 equiv of ZnCl2.[20]
The best reaction condition (Condition A, entry 1 in Table 1)
was applied to the reaction of 3-methoxybenzylzinc chloride (2d)
with propargyl difluorides bearing various types of substituents
at  (R1) and  (R2) positions (Scheme 3). The high selectivity
giving allene
3 was observed for the reaction of those
substituted with tertiary alkyl groups at  position (Scheme 3(a)).
Thus, the reaction of propargyl difluorides 1a–1e, which have a
tBu group at  position, all gave the corresponding fluoroallenes
3ad–3ed in high yields. The substituents R2 at  position are
primary alkyl groups including functionalized ones, CH2OMe
(3cd) and CH2CH2OTs (3ed). An aromatic group at  position is
also a good substituent giving the fluoroallene in high yield (1l in
Scheme 4(c)). The enantioselectivity was generally high, higher
than 90% ee in most cases. Other tertiary alkyl groups, 1-
adamantyl (1f), 1-methylcyclohexyl (1g), and 2-phenyl-2-propyl
(1h), which are sterically more demanding than tBu, gave the
corresponding fluoroallenes, 3fd, 3gd, and 3hd, with higher
(99%) enantioselectivity. The advantage of tertiary alkyl groups
at  position was observed for both high chemoselectivity and
enantioselectivity. The reaction of propargyl difluoride 1i, where
the R1 group at  position is a secondary alkyl (cyclohexyl), gave
a low yield (60%) of the fluoroallene 3id together with 7% of
dibenzylation product 6id (Scheme 3(b)), the latter being formed
by the Rh-catalyzed reaction[21] of 3id with benzylzinc 2d. The
selectivity giving fluoroallene is even lower (30%) with a smaller
secondary alkyl at  position, which is shown by the reaction of
propargyl difluoride 1j (R1 = iPr). Interestingly, the enantiomeric
purity of the fluoroallene products 3id and 3jd obtained was very
low, which may be related to the stereochemical pathway to
decide the enantioselectivity of the present reaction (vide infra).
Table 1. Catalytic asymmetric reaction of alkyne 1a with 3-methoxybenzylzinc
chloride (2d).[a]
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10.1002/anie.202109290
Angewandte Chemie International Edition
COMMUNICATION
MeO
the chiral diene ligand and tBu group on the difluoride substrate.
Because the ferrocenyl and R1 groups are not very close each
other, the substituent R1 must be large enough for this repulsion
to work well. This mechanism of stereocontrol is consistent with
the low enantioselectivity observed for the reaction of difluorides
1i (R1 = Cy) and 1j (R1 = iPr) shown in Scheme 3(b), where the
R1 is not a tertiary alkyl group.
[RhCl((R,R)-Fc-tfb)]2
(5.0 mol% Rh)
Ar
R1
R1
F
(a)
R2
•
+
R2
F
ZnCl2 (2.4 equiv)
THF, 25 °C, 14 h
(Condition A)
F
ClZn
1a-1h
2d
3ad–3hd: Ar = 3-MeOC6H4
1a: R1 = tBu, R2 = Hex
1b: R1 = tBu, R2 = CH2CH2Ph
1c: R1 = tBu, R2 = CH2OMe
Ar
Ar
1d: R1 = tBu, R2 = cyclohexylmethyl
1e: R1 = tBu, R2 = CH2CH2OTs
•
•
F
F
1f: R1 = adamantyl, R2 = Hex
Ph
3ad
3bd
1g: R1 = 1-methylcyclohexyl, R2 = Hex
1h: R1 = 2-phenyl-2-propyl, R2 = Hex
75% yield, 98% ee
85% yield, 96% ee
(Condition A)
R3
R3-ZnCl
2c–2j
Ar
+
•
(a)
F
Ar
Ar
OTs
Ar
F
F
1e
OTs
3ec–3ej
•
•
•
F
F
F
3ed
OMe
OTs
3cd
3dd
72% yield
98% ee
•
60% yield, 86% ee
71% yield, 94% ee
F
•
•
3ei: 69% yield
OTs
F
F
92% ee
3ec (Ar = C6H5):
47% yield, 96% ee
OTs
3ed (Ar = 3-MeOC6H4):71% yield, 94% ee
3ee (Ar = 4-MeOC6H4): 56% yield, 96% ee
3ef (Ar = 3-MeC6H4): 51% yield, 93% ee
3eg (Ar = 4-iPrC6H4): 53% yield, 94% ee
3eh (Ar = 4-ClC6H4): 65% yield, 99% ee
Ar
Ar
Ar
Ph
Me
•
•
•
3ej: 60% yield
F
F
30% ee
F
OTs
3fd
3gd
3hd
73% yield, 99% ee
90% yield, 99% ee
80% yield, 99% ee
X
X
R1
MeO
R1
F
(Condition A)
Ar
Hex
3id or 3jd
Ar
R2
+
R1
ZnCl
(b)
R1
R1
•
(Condition A)
X
R2
F
F
+
Hex
•
•
(b)
+
Hex
X
F
3
F
F
Ar
1a, 1d, 1f
1k: R1 = tBu, R2 = CH2Ph
2k: X = F, 2b: X = Cl
2l: X = OMe
ClZn
R1 = Cy (1i)
6id or 6jd
2d
R1 = Cy: 60% yield, 7% ee
R1 = iPr: 30% yield, <1% ee
iPr (1j)
X
7% yield
X
F
13% yield
OMe
•
•
•
•
F
F
X
F
X
Ph
F
F
Scheme 3. Asymmetric synthesis of fluorinated allenes catalyzed by
[RhCl((R,R)-Fc-tfb)]2. Scope of propargyl difluorides.[a]
OMe
3dk (X = F):
3fk:
3kk (X = F):
3al:
83% yield, 94% ee
3db (X = Cl):
99% yield, 95% ee
88% yield, 81% ee
67% yield, 93% ee (S) [RhCl(L4*)]2 as catalyst
3kb (X = Cl):
77% yield, 88% ee
82% yield, 88% ee
Cl
Benzylic zinc reagents with some other substituents on the
benzene ring 2c–2h gave the corresponding fluoroallenes 3ec–
3eh with high enantioselectivity (93%–99% ee) in the reaction
with propargyl difluoride 1e (Scheme 4(a)). The OTs functionality
is installed into the side chain of 1e for easier separation of
allene enantiomers at their HPLC analysis as well as for further
transformation of the allene products. Neopentylzinc chloride (2i)
was used successfully for the present reaction, which gave the
corresponding fluoroallene 3ei in 69% yield with 92% ee.
MeZnCl[22] also gave the fluoroallene 3ej although the
enantioselectivity was not as high (30% ee). A complex mixture
was formed in the reaction with EtZnCl, which is probably due to
the -hydrogen elimination from ethyl-Rh intermediate. The
arylzinc reagents, 2k and 2b, which are disubstituted with F and
Cl, respectively, at meta,meta-positions, can be also used for the
present reaction to give the corresponding arylated fluoroallenes
with high enantioselectivity (Scheme 4(b). see also Scheme 2).
The absolute configuration of fluoroallene product 3lh, which
was obtained by the reaction of propargyl difluoride 1l (R2 = 3,5-
F2C6H3) with benzylic zinc 2h, was determined to be R by X-ray
crystal analysis (CCDC 2063773) (Scheme 4(c)). It is
remarkable that the allenes 3kk and 3lc, which were produced
by the reactions shown in Scheme 4(b) and Scheme 4(c),
respectively, are a pair of enantiomers. The R configuration for
3lc and S configuration for 3kk are rationalized by the
stereochemical pathway shown in Scheme 5, where pro-R
fluoride participates in the -F elimination from the alkenyl–Rh
intermediate. The participation of pro-S fluoride would suffer
from a steric repulsion between one of the ferrocenyl groups on
F
Ph
F
(Condition A)
(c)
F
•
•
F
F
F
1l
F
F
3lc: 94% yield
83% ee (R)
F
+
3lh: 73% yield
89% ee (R)
F
ArCH2ZnCl
2c: Ar = Ph
2h: Ar = 4-ClC6H4
(>99% ee for X ray analysis)
Scheme 4. Asymmetric synthesis of fluorinated allenes catalyzed by
[RhCl((R,R)-Fc-tfb)]2. Scope of organozinc reagents.[a]
Fc
Fc
Fc
R3
R2
Rh
F
pro-R
•
R3
R2
Rh
F
F
F
R3
R2
F
pro-R
(R)-3lc:
Fc
favorable R2 = Ar, R3 = CH2Ph
top view
front view
(S)-3kk:
R2 = CH2Ph, R3 = Ar
F
F
Fc
F
pro-S
F
F
R3
R2
Rh
F
F
R3
R2
•
Fc
Fc
Fc
(R,R)-Fc-tfb
disfavorable
Fc = ferrocenyl
Scheme 5. Stereochemical pathway in the asymmetric synthesis of fluorinated
allenes catalyzed by [RhCl((R,R)-Fc-tfb)]2.
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10.1002/anie.202109290
Angewandte Chemie International Edition
COMMUNICATION
OMe
iPr
Angew. Chem. 2016, 128, 9108; d) D. Qian, L. Wu, Z. Lin, J. Sun, Nat.
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S. Riedel, B. Nieto-Ortega, F. J. Ramírez, J. T. López Navarrete, J.
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637.
R
a)
d)
Cl
•
•
•
F
F
F
3eg
3ei
3eh
7
10
OTs
b)
CH(COOMe)2
c)
or 3ee
O
•
F
•
N
8
F
[4]
[5]
9
I
O
a) 3eg (94% ee), NaCH(COOMe)2,
DME, 79% yield, 92% ee. b) 3ei
(92% ee), KN(CO)2C6H4, DMF,
71% yield, 92% ee. c) 3eh (99%
ee), NaI, acetone, 99% yield, 99%
ee. d) 3ee (96% ee), NaH, THF,
91% yield, 96% ee. e) 3al (88% ee),
NIS, MeCN, 82% yield, 88% ee.
OMe
OMe
e)
I
•
F
F
11
OMe
3al
OMe
Scheme 6. Derivatization of the fluoroallene products 3.
Taking advantages of the tosylate as a leaving group, those
fluoroallenes bearing a tosylate were readily converted into
malonate 7, phthalimide 8, iodide 9, and conjugated alkene 10
without serious loss of their enantiomeric purity (Scheme 6). The
iodonium-induced cyclization giving indene[23] was successfully
applied to the chiral arylallene 3al to give the chiral indene 11
with a quaternary carbon center with 88% ee.
In summary, we have developed a new type of catalytic
asymmetric reaction producing axially chiral fluorinated allenes
with high
% ee, where the enantioposition-selective -F
elimination from an alkenyl-Rh intermediate[24] is a key step in
[6]
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Acknowledgements
This work was supported by funding from Nanyang Techno-
logical University and the Singapore Ministry of Education (AcRF
MOE 2017-T2-1-064).
Keywords: axially chiral allene • asymmetric defluorination •
chiral diene ligand • rhodium catalyst
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Angewandte Chemie International Edition
COMMUNICATION
M. Zhao, C.-C. Shan, Y.-H. Xu, T.-P. Loh, Angew. Chem. Int. Ed. 2019,
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the transmetalation between alkenyl-Rh intermediate B and ZnCl2
generating alkenylzinc, which would produce racemic product 3ad
through -F elimination, is not taking place in the present reaction.
[21] An addition/elimination mechanism has been proposed for this type of
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[22] The use of Me2Zn instead of MeZnCl (MeMgBr + ZnCl2 (2.2 eq)) gave
80% yield of 3ej with 15% ee, and Me2Zn + MgCl2 (1.0 eq) gave 82%
yield of 3ej with 22% ee.
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[24] The -elimination to form a Rh–F intermediate was observed by 19F
NMR in a stoichiometric reaction of propargyl difluoride (1a, 1 equiv)
with 3,5-Cl2C6H3B(OH)2 (0.5 equiv) and [Rh(OH)(cod)]2 (1 equiv of Rh).
For details, see Supporting Information. For NMR studies on F–Rh
complexes see, J. Vincente, J. Gil-Rubio, D. Bautista, A. Sironi, N.
Masciocchi. Inorg. Chem. 2004, 43, 5665.
[16] For the preparation of ArZnCl/ZnCl2, see Supporting Information.
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Text for Table of Contents
Jia Sheng Ng and Tamio Hayashi*
Page No. – Page No.
Asymmetric Synthesis of Fluorinated
Allenes by Rhodium-Catalyzed
Enantioselective
Alkylation/Defluorination of Propargyl
Difluorides with Alkylzincs
((Insert TOC Graphic here))
Layout 2:
COMMUNICATION
F
F
Jia Sheng Ng and Tamio Hayashi*
[RhCl((R,R)-Fc-tfb)]2
(5.0 mol% Rh)
F
R1
R1
F
R3
R2
R2 + R3–ZnCl
•
Page No. – Page No.
F
F
ZnCl2 (2.4 equiv)
THF, 25 °C, 14 h
F
[Rh]
Fc
Asymmetric Synthesis of Fluorinated
Allenes by Rhodium-Catalyzed
Enantioselective
up to 99% ee
F
R3
Fc
R1 = tertiary alkyls
R2, R3 = alkyl, aryl
enantioselective
b-F elimination
(R,R)-Fc-tfb
Fc = ferrocenyl
F R1
R2
Alkylation/Defluorination of Propargyl
Difluorides with Alkylzincs
The reaction of propargyl difluorides R1CF2C≡CR2 with alkylzincs R3ZnCl giving
axially chiral fluorinated allenes R1FC=C=CR2R3 with high enantioselectivity (up to
99% ee) was found to be catalyzed by a chiral diene/rhodium complex. A key step
in the catalytic cycle is selective elimination of one of the enantiotopic fluorides at -
position of an alkenyl–Rh intermediate which is generated by regioselective addition
of R3–Rh onto the triple bond of the starting difluorides.
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