Copper Hydride Catalyzed Enantioselective Synthesis of Axially Chiral 1,3-Disubstituted Allenes

Article abstract of DOI:10.1021/jacs.9b07582

The general enantioselective synthesis of axially chiral disubstituted allenes from prochiral starting materials remains a long-standing challenge in organic synthesis. Here, we report an efficient enantio- and chemoselective copper hydride catalyzed semireduction of conjugated enynes to furnish 1,3-disubstituted allenes using water as the proton source. This protocol is sufficiently mild to accommodate an assortment of functional groups including keto, ester, amino, halo, and hydroxyl groups. Additionally, applications of this method for the selective synthesis of monodeuterated allenes and chiral 2,5-dihydropyrroles are described.

Full text of DOI:10.1021/jacs.9b07582

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Communication
Copper Hydride-Catalyzed Enantioselective
Synthesis of Axially Chiral 1,3-Disubstituted Allenes
Liela Bayeh-Romero, and Stephen L. Buchwald
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b07582 • Publication Date (Web): 17 Aug 2019
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Copper Hydride-Catalyzed Enantioselective Synthesis of Axially
Chiral 1,3-Disubstituted Allenes
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Liela Bayeh-Romero and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
ABSTRACT: The general enantioselective synthesis of axially chiral disubstituted allenes from prochiral starting materials
remains a long-standing challenge in organic synthesis. Here, we report an efficient enantio- and chemoselective copper hydride-
catalyzed semi-reduction of conjugated enynes to furnish 1,3-disubstituted allenes using water as the proton source. This protocol is
sufficiently mild to accommodate an assortment of functional groups including keto, ester, amino, halo, and hydroxyl groups.
Additionally, applications of this method for the selective synthesis of mono-deuterated allenes and chiral 2,5-dihydropyrroles are
described.
While the utility of chiral allenes has been widely explored,
Allenes form a distinctive class of compounds capable of
the selective synthesis of these valuable materials still remains
exhibiting axial chirality. They are represented in over 2,900
a challenge in organic synthesis.3a, 7 Traditional approaches to
natural metabolites and synthetic compounds, and have been
access enantioenriched allenes most commonly start from
studied with regard to biological activity for over forty years.1
chiral, enantioenriched precursors wherein the allene product
The introduction of allenes into steroids, prostaglandins,
is generated through nucleophilic displacement, rearrangement
carbacyclins, and unnatural amino acids and nucleosides has
or elimination with central-to-axial chirality transfer (Figure 1)
been shown to increase the metabolic stability, bioavailability,
or through resolution of racemic allenes. More recently,
several methods have employed achiral or racemic starting
materials in catalytic asymmetric versions of these reactions to
access the desired product using catalysts bearing chiral
ligands. However, the majority of these reports target the
synthesis of tri- or tetrasubstituted allenes.8
and potency of these bioactive compounds.2 Additionally,
these cumulated dienes have found use in molecular materials
and as synthetic intermediates in complex chemical syntheses
as substrates due to their substituent-loading capability and
enhanced reactivity under mild reaction conditions. Their
tranformation often takes advantage of axial-to-central
chirality transfer to generate one or more new stereogenic
centers.3 Finally, chiral allenes have also been explored in
asymmetric autocatalysis and as ligands for the development
of enantioselective transformations.4-6
The direct catalytic conversion of prochiral 1,3-enynes to
enantioenriched allenes has become a practical synthetic
strategy in recent years, owing to the accessibility of these
substrates.9 Early reports by Hayashi describe the direct
catalytic and enantioselective conversion of 1,3-enynes to
boryl-, silyl-, or aryl allenes via palladium or rhodium
catalysis.8a–d Since then, methods detailing the stereoselective
transformations of enynes, including reports by Loh, Feng,
Tang, Sun and Malcolmson, have provided novel routes to
enantioenriched allenes containing esters, lactones or
amines.8g, l, n, p, 10
X
R2
X
R2
Central-to-Axial
Chirality Transfer
Asymmetric
Catalysis
R2
H
Achiral or Racemic
Starting Materials
H
•
H
R1
H
R1
X
R2
Traditional Methods
Less Explored
Route
(Substitution, Elimination,
Rearrangement, etc.)
Disubstituted
Allenes
R1
H
Y
H
O
CO2Me
HO2C
•
BnO
OH
H
Me
H
H
•
•
H
n-C10H21
H
HO
O
HO
The LCuH-catalyzed hydrofunctionalization of 1,3-enynes to
access enantioenriched allenes was first reported by the
Hoveyda group wherein trisubstituted allenyl boronate
derivatives are generated in high yield and enantioselectivity
(Scheme 1a).11 Shortly thereafter, the Ge and Engle groups
independently disclosed their own reports of enyne
hydroboration, followed by Ge’s report of the catalytic
asymmetric hydroarylation of enynes to provide access to
quinoline-substituted allenes.12–14
Laballenic Acid
(Seed oil natural product)
Synthetic Intermediate
(Synthesis of (+)-varitriol)
Enprostil
(Inhibitor of gastric HCl secretion)
EtO2C
H
Et
H
HO
H
•
•
•
H
H
H
TIPSO
(CH2)5CH3
Me
CO2H
CO2Me
Synthetic intermediate
(Synthesis of clavepictines A and B)
Synthetic intermediate
(Synthesis of
Isolated from Sapium japonicum
(Anti-fungal agrochemical)
(-)-trans-whiskey lactone)
Figure 1. Synthetic strategies for the construction of
enantioenriched allenes and representative examples of
valuable 1,3-disubstituted allenes
Despite these recent advances, fewer reports describe the
catalytic synthesis of enantioenriched 1,3-disubstituted allenes
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15–21
from prochiral or racemic precursors.10,
While these
semi-reduction of 1,3-enynes to enantioenriched disubstituted
1
2
3
4
5
6
7
8
methods have offered elegant and innovative routes to this
class of allenes, the vast majority of them provide access to a
allenes has only been demonstrated with the stoichiometric use
of chiral metal reducing agents.25 Herein, we report the
asymmetric catalytic semi-reduction of 1,3-enynes to furnish
axially chiral allenes enabled by CuH-catalysis.
18
limited scope of products including allenyl esters,16,
16, 20
alcohols,19 and amines.10,
This modest scope is perhaps
due to difficulty in controlling the stereochemical outcome of
a three-carbon axis of chirality possessing two hydrogen
substituents without an additional functional group handle.
Consequently, there persists an unmet need for a general
strategy to access a broad range of 1,3-disubstituted axially
chiral allenes.
We began our studies utilizing 1,2-bis((2S,5S)-2,5-
diphenylphospholano)ethane [(S,S)-Ph-BPE] in combination
with Cu(OAc)2 and dimethoxy(methyl)silane (DMMS) to
generate a chiral LCuH complex previously shown to engage
1,3-enyne 1a (Table 1).22 At room temperature with t-BuOH
as the proton source, the complete consumption of 1a occurred
yielding a complex mixture consisting primarily of products
from the unselective hydrogenation of the desired product,
allene 4a (entry 1). Decreasing the reaction temperature to –10
ºC slowed the over-reduction and provided 4a in 34% yield
and 60:40 enantiomeric ratio (er) (entry 2). A subsequent
screen of several ethereal solvents indicated that both chemo-
and enantioselectivity were enhanced by replacing THF with
1,2-dimethoxyethane (DME) (entries 3–5).
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Scheme 1. Precedent for the Proposed Asymmetric LCuH-
Catalyzed Semi-Reduction of 1,3-Enynes
(a) Representative LCuH-catalyzed transformations of conjugated enynes to yield allenes
R2
Cu(OAc)2 (2.5– 5 mol%),
(R,R)-Ph-BPE (2.5– 5 mol%),
R2
•
Hoveyda, 2018
(ref. 11)
(pin)B
H
•
R1
H– B(pin) (2 equiv)
R1
Hydroboration
Up to 80% yield
99:1 er
R3
Cu(OAc)2 (4 mol%),
(S,S)-Ph-BPE (6 mol%),
(EtO)2MeSi– H (2 equiv)
Table 1. Reaction Optimizationa
R2
H
R2
•
S. Ge, 2018
(ref. 14)
N
•
R1
R3
N+
R1
O-
Up to 95% yield
>99:1 er
Hydroarylation
(b) Initial strategy for the enantioselective LCuH– catalyzed synthesis of allenes
T
(ºC)
Proton
Source
%
%
(Previous work)
Entry
Solvent
THF
Silane
erc
Conv. Yieldb
O
R2
Cu(OAc)2 (5 mol%),
(S,S)-Ph-BPE (6 mol%),
R2
R2

R3
R4
t-BuOH
(1.5 equiv)


1
2
3
4
5
6
7
8
9e
23
DMMS 100
DMMS 100
0
–
R4
R3
R1
H
•
R1
R3Si– H
(via SE2’)
1
R1
HO
CuL*
t-BuOH
(1.5 equiv)
C– C Bond
Formation
3
2
–10
THF
34 60:40
36 87:13
26 92:8
36 96:4
68 99:1
90 99:1
90 >99:1
Ph
Ph
Enantioenriched
Alcohols
P
t-BuOH
(1.5 equiv)
P
(This work)
–10 MTBE d
DMMS
DMMS
DMMS
64
67
50
R2
Ph
Ph
(S,S)-Ph-BPE
X– H

R1
H
•
1,4-
–10
t-BuOH
Dioxane (1.5 equiv)
C– H Bond
Formation
H
4
Enantioenriched
Allenes
t-BuOH
DME
Potential Challenges:
–10
–10
–10
–10
–10
(1.5 equiv)
Regioselectivity:
Direct silylation of proton source:
i-PrOH
DME
CuH
H
H
H
H
R2
DMMS 100
DMMS 100
DMMS 100
X– SiR3 + H2
X– H
R2
R1
R2
(1.5 equiv)
R3Si– H
vs.
vs.
•
R1
R1
H
H
H
H
Overreduction of the allene product:
i-PrOH
DME
R2
(1.1 equiv)
Enantioselectivity?
H
CuH
H
R1
R1
+
H2O
DME
R1
H
R2
R2
•
R2
•
R3Si– H
X– H
H
H
H
H
H
R1
H
H
(0.55 equiv)
H
H2O
DME
TMCTS 100 90f >99:1
(0.52 equiv)
In the course of our ongoing studies on the hydroalkylation of
1,3-enynes with imines, we serendipitously discovered an
alternative strategy for the synthesis of 1,3-disubstituted
allenes (Scheme 1b). Analogous to our previous report on the
hydroalkylation of conjugated enynes with ketones,22
enantioenriched allenyl copper intermediates 2 are generated
via hydrocupration of an achiral 1,3-enyne starting material
(1). However, trapping of the allenyl copper species 2 directly
with a proton, instead of a ketone (which favors the alternative
SE2’ reaction pathway to yield -adduct 3), would provide
access to axially chiral 1,3-disubstituted allenes (4). Potential
challenges in developing this reaction include avoiding the
unproductive silylation of the protonating reagent,23
controlling the regioselectivity24 and enantioselectivity of the
process, and preventing further reduction of the allene product
in the presence of the copper hydride catalyst. To date, the
a Conditions: Reactions were carried out under N2 atmosphere.
0.2 mmol enyne (1 equiv), copper(II) acetate (3 mol%), (S,S)-Ph-
BPE (3.3 mol%), silane (4 equiv) in solvent (0.4 mL). b Yield was
determined by 1H NMR spectroscopy of the crude reaction
c
mixture, using mesitylene as an internal standard. Enantiomeric
ratio was determined by GC analysis, and the absolute
configuration of 4a was determined by analogy to desilylated 4f
d
(see the Supporting Information for more details). MTBE =
e
methyl tert-butyl ether.
Reaction was run with 1 mol%
copper(II) acetate and 1.1 mol% (S,S)-Ph-BPE over 16.5 h
instead. f Reported as an average of two isolated yields.
The use of a sterically less hindered proton source, i-PrOH,
provided improved conversion and enantiomeric ratio of
product 4a. Moreover, we found that by decreasing the
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quantity of i-PrOH to 1.1 equivalents minimized the amount of
overreduction that was observed (entries 6–7). As the use of a
less hindered proton source proved beneficial for both yield
and er, we next examined the use of H2O (0.55 equiv) which
resulted in the efficient delivery of both protons in the enyne
semi-reduction (entry 8). Further, we found that substituting
groups are tolerated under the reaction conditions including
potentially reducible groups such as alkyl chlorides (4d) and
ketones (4e) as well as ethers (4f, 4i), amines (4j, 4l), and
various heterocycles (4i, 4k, 4n, 4o). Substrates containing
unprotected alcohols are not only tolerated, but the unhindered
primary alcohol of enyne 1g, itself, serves as a proton source
in the reduction, permitting the use of only 0.25 equivalents of
H2O additive to furnish allene 4g. The reactivity and
selectivity of the sterically more encumbered enyne 1h,
bearing an unprotected propargylic alcohol, were unaffected,
providing allenyl alcohol 4h with 88% yield and >99:1 er.
While substrates containing free N–H bonds react with high
yield, the allene products are produced with a diminished er
(4m, n). In the case of 1n it was demonstrated that the use of
the protected variant, 1o, provided significantly improved
results (4o). Finally, this protocol exhibits excellent catalyst
control in the semi-reduction of chiral enyne 1p to furnish
either diastereomer of allene 4p depending on the enantiomer
of ligand used.
1
2
3
4
5
6
7
8
DMMS
with
0.5
equiv
of
2,4,6,8-
tetramethylcyclotetrasiloxane (TMCTS) and decreasing the
catalyst loading to 1 mol% provided improved reaction
conditions for the enantioselective semi-reduction of 1,3-
enyne 1a affording the desired product (R)-4a in 90% isolated
yield and >99:1 er (entry 9).
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Table 2. Substrate Scope of the LCuH–Catalyzed
Asymmetric Semi-Reduction of 1,3-Enynes to Allenesa
Our initial efforts to effect the asymmetric semi-reduction of
internal 1,3-enyne substrates proved considerably more
challenging. This difficulty was presumably due, in part, to an
increased energetic barrier to hydrocupration, resulting in low
conversion (possibly owing to unproductive silylation of the
proton source) as well as, in some cases, competitive
overreduction of the initially-formed allene products.27 To
ameliorate these issues, we found that the utilization of a
protocol with the slow addition of water was essential (Table
3). The reaction of ester-containing enyne 1q occurred in
moderate yield, largely due to competitive overreduction of
the desired product, 4q. The antifungal antibiotic Terbinafine
(1r) was cleanly transformed to 4r in 68% yield and 99:1 er,
although it necessitated an increase in H2O and TMCTS
loading.28 The direct conversion of fatty acid natural product
1s to laballenic acid (4s), a seed oil natural product isolated
from the Leonitis nepetaefolia plant could also be
accomplished 29–32 The in situ protection of carboxylic acid 1s
with DMMS (to furnish the corresponding silyl ester) at room
temperature was carried out, followed by slow addition of
water at –10 °C to deliver laballenic acid in 50% yield and
93:7 er.
Table 3. Select Examples of the LCuH–Catalyzed
Asymmetric Semi-Reduction of Internal Enynes to
Allenesa
a
Reactions were carried out under N2 atmosphere at –10 ºC.
Isolated yields and enantiomeric ratios are reported as an average
b
1
of two independent runs. Yield was determined by H NMR
spectroscopy using mesitylene as an internal standard due to the
c
d
volatility of the product. With 0.25 equiv H2O instead. Yield
and diastereomeric ratio reported for a single run.
Next, we surveyed the generality of the LCuH-catalyzed
asymmetric semi-reduction of an assortment of terminal 1,3-
enynes (Table 2).26 Unfunctionalized substrates are efficiently
converted to the corresponding allenes with good yield and
exceptional er (4a–c). Enynes bearing a variety of functional
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analogs, but also in mechanistic studies and protein
Page 4 of 8
crystallography.33 Substitution of H2O for D2O selectively
delivers enantioenriched mono-deuterated products, as
exhibited in the conversion of enyne 1t to allene 5 with 98:2
D/H incorporation (Scheme 2a). This protocol represents a
new strategy for the deuterium labeling of allenes, employing
an affordable, easy to handle and abundant deuterium source.
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4
5
6
7
8
Scheme 2. Applications of the LCuH-Catalyzed
Asymmetric Reduction for Deuterium Incorporation and
Heterocycle Synthesis
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a
Reactions were carried out under N2 atmosphere at –10 ºC,
H2O was added over a 16 hour time period. Isolated yields and
enantiomeric ratios are reported as an average of two independent
runs. Reaction required a 1 hour pre-stir at room temperature
b
Additionally, enantioenriched allenyl alcohols and amines are
known to serve as valuable synthetic intermediates toward the
prior to addition of water at –10 ºC
production of chiral heterocycles including dihydrofurans and
Based on previous mechanistic studies and DFT
34, 35
dihydropyrroles.3h,
Taking advantage of the highly
calculations,11,
we propose the following mechanism
22
selective nature of gold-catalyzed cycloisomerization
detailed in Figure 2. After generation of the chiral LCuH
complex I, enantioselective hydrocupration of enyne II affords
a chiral propargylic copper species (III). This undergoes a
stereospecific 1,3-isomerization to yield allenyl copper
intermediate V. Next intermediate V is protonated to furnish
the final product, allene VI. -Bond metathesis between VII
and silane (VIII) results in the formation of silanol IX and
regeneration of I. As less than a full equivalent of water is
utilized in this process, we propose that silanol IX can also
facilitate proto-demetallation, producing siloxane X.
chemistry, -aminoallene 4l furnished 2,5-dihydropyrrole 6
with complete axial-to-point chirality transfer (Scheme 2b).36,
37
In summary, we have developed
a
LCuH-catalyzed
asymmetric semi-reduction of 1,3-enynes to supply highly
enantioenriched 1,3-disubstituted allenes in up to 98% yield
and >99:1 er. This chemistry benefits from the functional
group tolerance afforded by the mild reducing nature of LCuH
catalysts and employs only 1–2 mol% catalyst loading.
Moreover, the utilization of substoichiometric quantities of
H2O as the proton source and TMCTS as the hydride source
provides an efficient protocol for the hydrogenation of
terminal 1,3-enynes. The reduction of internal conjugated
enynes is enabled via slow addition of water and has been
demonstrated through the late-stage derivatization of antibiotic
Terbinafine and the synthesis of the seed oil natural product,
laballenic acid. Furthermore, this protocol provides an
efficient synthetic route for the construction of deutero-allenes
as well as aza-heterocycles.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Figure 2. Proposed catalytic cycle for the LCuH-catalyzed
conversion of 1,3-enynes to allenes
General procedural information and characterization data (PDF)
NMR Spectra (PDF)
SFC, GC and HPLC Traces (PDF)
Two examples demonstrating further applications of this
methodology are depicted in Scheme 2. The incorporation of
deuterium into molecular scaffolds is pervasive not only in the
pharmaceutical industry, due to the enhanced metabolic
stability and safety imparted by corresponding deutero-
AUTHOR INFORMATION
Corresponding Author
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Kinsman, L.; Angiolini, S. M.; Rosair, G. M.; Lee, A.-L., Gold(I)–
* sbuchwal@mit.edu
Catalysed Hydroarylation of 1,3-Disubstituted Allenes with Efficient
Axial-to-Point Chirality Transfer. Chem. Eur. J. 2018, 24, 7002–
7009.
(4) Sato, I.; Matsueda, Y.; Kadowaki, K.; Yonekubo, S.; Shibata, T.;
Soai, K., Highly Enantioselective Asymmetric Autocatalysis of
Pyrimidin-5-yl Alkanol Induced by Chiral 1,3-Disubstituted
Hydrocarbon Allenes. Helv. Chim. Acta 2002, 85, 3383–3387.
(5) Cai, F.; Pu, X.; Qi, X.; Lynch, V.; Radha, A.; Ready, J. M.,
Chiral Allene-Containing Phosphines in Asymmetric Catalysis. J. Am.
Chem. Soc. 2011, 133, 18066–18069.
1
2
3
4
5
6
7
8
Funding Sources
The Arnold and Mabel Beckman Foundation
The National Institutes of Health (R35-GM122483)
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
9
Research reported in this publication was supported by the Arnold
and Mabel Beckman Foundation (LBR) and the National
Institutes of Health (R35-GM122483). The authors would like to
thank Nippon Chemical Industrial Co., Ltd., Solvias AG, and
Takasago International Corporation for donations of ligands used
in this project. We thank Dr. M. Kumar for his assistance with
HRMS analysis and R. Liu, Dr. A. Thomas and Dr. S. McCann
for their counsel in the preparation of this manuscript. We are
grateful to E. Tsai and Drs. S. Guo and Y. Yang for supplying
some of the starting materials used in this project and the National
Institutes of Health for a supplemental grant for the purchase of
supercritical fluid chromatography (SFC) equipment (GM058160-
17S1). The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
(6) Vanitcha, A.; Damelincourt, C.; Gontard, G.; Vanthuyne, N.;
Mouriès-Mansuy, V.; Fensterbank, L., Bis-phosphine allene ligand:
coordination chemistry and preliminary applications in catalysis.
Chem. Comm. 2016, 52, 6785–6788.
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(7) For selected reviews on the asymmetric synthesis of allenes, see:
(a) Krause, N.; Hoffmann-Röder, A., Synthesis of allenes with
organometallic reagents. Tetrahedron 2004, 60, 11671–11694. (b)
Brummond, K. M.; DeForrest, J. E., Synthesizing Allenes Today
(1982–2006). Synthesis 2007, 2007, 795–818. (c) Yu, S.; Ma, S., How
easy are the syntheses of allenes? Chem. Comm. 2011, 47, 5384–
5418. (d) Ye, J.; Ma, S., Conquering three–carbon axial chirality of
allenes. Org. Chem. Front. 2014, 1, 1210–1224. (e) Shirakawa, S.;
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Hayashi, T.; Tokunaga, N.; Inoue, K., Rhodium-Catalyzed
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M.; Ito, A.; Yoshida, K.; Hayashi, T., Synthesis of 2,5-
Bis(binaphthyl)phospholes and Phosphametallocene Derivatives and
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of Conjugated Enynes: Enantioselective Synthesis Enabled by
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Insights Regarding Stereochemical Integrity of Cu–Allenyl
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(13) Gao, D.–W.; Xiao, Y.; Liu, M.; Liu, Z.; Karunananda, M. K.;
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Allenyl Boronates. ACS Cat. 2018, 8, 3650–3654.
(14) Yu, S.; Sang, H. L.; Zhang, S.–Q.; Hong, X.; Ge, S., Catalytic
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(21) These products are also accessible via protodeboration of the
allenyl-Bpin products from Refs. 11–13 using Cu(OAc)2 (5 mol%),
dppe (5 mol%) and methanol (2 equiv), as described in the Supporting
Information of Ref. 11.
(22) Yang, Y.; Perry, I. B.; Lu, G.; Liu, P.; Buchwald, S. L.,
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(15) Oku, M.; Arai, S.; Katayama, K.; Shioiri, T., Catalytic
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Transfer Catalyzed Conditions. Synlett 2000, 2000, 493–494.
(16) Trost, B. M.; Fandrick, D. R.; Dinh, D. C., Dynamic Kinetic
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(17) Wei, X.-F.; Wakaki, T.; Itoh, T.; Li, H.-L.; Yoshimura, T.;
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Palladium–Catalyzed Asymmetric Synthesis of Axially Chiral
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A Synergistic Effect of Dibenzalacetone on High
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of ketones and alk–2–en–4–yn–1–ols with
a
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(33) Gant, T. G., Using Deuterium in Drug Discovery: Leaving the
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(34) Ma, S., Transition Metal–Catalyzed/Mediated Reaction of
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(37) Morita, N.; Krause, N., Gold-Catalyzed Cycloisomerization of
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3–O–benzyl–1,2–O–cyclohexylidene–α–D–glucofuranose complex;
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(26) For examples of substrates which gave poor reactivity or
selectivity, see the Supporting Information.
(27) Using the standard reaction conditions detailed in Table 2 with
5 mol% catalyst loading, substrate 1q gave only 51% conversion with
1
1
24% H NMR yield of 4q and a 20% combined H NMR yield of
over-reduction products. Additionally, using the same conditions with
2 mol% catalyst loading, substrate 1r gave only 33% conversion with
33% 1H NMR yield of 4r.
(28) McClellan, K. J.; Wiseman, L. R.; Markham, A., Terbinafine.
An update of its use in superficial mycoses. Drugs 1999, 58, 179–202.
(29) Tlili, N.; Elfalleh, W.; Saadaoui, E.; Khaldi, A.; Triki, S.; Nasri,
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For Table of Contents Only:
R2
R2
• Mild Conditions
• Wide Substrate Scope
• Regioselective
L*CuH
R1
H
•
H2O (0.52 equiv)
R1
• Control of Axial Chirality
H
1,3-Enynes
Enantioenriched
Allenes
Me
Me
Me
Me
OH
Boc
H
•
H
•
H
•
N
N
•
Ph
Bn
H
90% yield,
>99:1 er
88% yield,
>99:1 er
91% yield,
99:1 er
68% yield,
99:1 er
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