Rh-Catalyzed Stereospecific Synthesis of Allenes from Propargylic Benzoates and Arylboronic Acids

Article abstract of DOI:10.1021/acs.orglett.6b00793

An enantiospecific approach to the synthesis of optically active, trisubstituted allenes from chiral propargylic benzoates and arylboronic acids has been developed. The transformation is catalyzed by a Rh-(P,olefin) complex formed in situ from [{Rh(cod)Cl

Full text of DOI:10.1021/acs.orglett.6b00793

Letter
pubs.acs.org/OrgLett
Rh-Catalyzed Stereospecific Synthesis of Allenes from Propargylic
Benzoates and Arylboronic Acids
Jonathan Ruchti and Erick M. Carreira*
̈ ̈ ̈
Laboratorium fur Organische Chemie, ETH Zurich, HCI H335, Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland
*
S Supporting Information
ABSTRACT: An enantiospecific approach to the synthesis of optically active,
trisubstituted allenes from chiral propargylic benzoates and arylboronic acids
has been developed. The transformation is catalyzed by a Rh−(P,olefin)
complex formed in situ from [{Rh(cod)Cl} ] and a readily available
2
phosphoramidite ligand. The method furnishes an assortment of diverse
allenes in high yields and excellent enantiospecificity under mild conditions.
6
llenes are an important class of compounds due to their
from the asymmetric addition of terminal alkynes to aldehydes
A
unique reactivity and their use as building blocks in
complex molecule synthesis. The transition-metal-catalyzed
S 2′ reaction between propargyl alcohol derivatives and
or the reduction of α,β-alkynyl ketones by the methods
described by Corey, Noyori, or Midland.
1
7
N
Our investigations commenced by studying the Rh-catalyzed
reaction between propargylic carbonates and phenylboronic
acid (2a) as test substrates. In the presence of [{Rh(cod)Cl}2],
ligand 4 (1:1 ligand/Rh), and Cs CO in 1,4-dioxane/water,
organometallic reagents constitutes one of the most important
approaches for the preparation of optically active allenes.
Herein, we disclose a preparation of enantioenriched allenes
from chiral propargylic benzoates and arylboronic acids. The
reaction employs a Rh-catalyst formed in situ from a simple,
achiral phosphoramidite ligand and commercially available
2
2
3
the reagents were observed to undergo reaction to furnish the
corresponding allene. However, under these conditions, no
chirality transfer was observed, leading to product formation as
a racemate. After extensive experimentation, we observed that
variation of the solvent, ligand (e.g., 4−10), ligand-to-metal
ratio, and base had a significant impact on the yield and
enantiospecificity of the process. Propargylic benzoates were
found to give comparable results as carbonates (see Supporting
[
{Rh(cod)Cl} ]. This method allows access to chiral,
2
trisubstituted allenes in high enantiomeric excess from the
corresponding propargylic alcohols (eq 1). As such, the Rh-
Information for an example) while 4-NO -benzoates gave the
2
products with lower selectivity. Accordingly, when the reaction
between propargylic benzoate 1a (96% ee) and phenylboronic
acid (2a) was conducted in 1,2-dichloroethane as solvent with
2
9
:1 4/Rh(I) and K PO as base, full conversion to adduct 3a in
8% es was observed (Table 1, entry 1). Following a screening
3 4
catalyzed synthesis of chiral allenes from widely available
boronic acids is complementary to related, previously reported
Cu- and Pd-catalyzed reactions. Furthermore, to the best of
of a number of other ligands (5−10), phosphine-olefin
phosphoramidite 4 was identified as the optimal ligand (see
Supporting Information for details).
3
our knowledge, a transition-metal-catalyzed, enantiospecific
synthesis of chiral, trisubstituted allenes from propargyl alcohol
derivatives and arylboronic acids has not been reported.
The traditional approaches to allenes from propargyl
electrophiles prescribe the use of stoichiometric amounts of
reactive organometallic reagents as coupling partners, derived
from In(III), Zn(II), Mg(II), and Cu(I). More recently, alkyl-,
vinyl-, and arylboron reagents have been used in the
preparation of chiral allenes from enantioenriched propargylic
8
With the optimal reaction conditions identified, the scope of
the method was examined (Scheme 1). Propargylic benzoates
(
ee ≥ 96%) 1a−j were prepared by the asymmetric addition of
6a
terminal alkynes to aldehydes and subsequent benzoylation.
Benzoate 1k was accessed through CBS-reduction of the
7d
corresponding α,β-ynone. Reaction of these benzoates with
various arylboronic acids 2 gave allenes 3 in good to excellent
yields, and the observed selectivities were high (≥90% es) in all
cases. The propargylic electrophiles can be substituted with a
protected amine (3f−3h), ester (3a−3e), or alkyl bromide
(3k). Electron-rich (3c, 3d, 3h) and electron-poor (3f, 3i, 3j)
arylboronic acids may serve as coupling partners. Ortho-
3
alcohol derivatives under Pd- or Cu-catalysis. The sole
example involving Rh-catalysis employs alkynyl epoxides as
electrophiles and arylboronic acids, in a reaction displaying high
4
,5
regio- and stereoselectivity to give allenes. However, the
requisite starting materials, namely optically active alkynyl
epoxides, are not readily accessible, requiring a multistep
sequence of reactions for their synthesis. Enantioenriched
propargylic alcohols on the contrary may be readily accessible
Received: March 18, 2016
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b00793
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Selected Ligand Screening Studies
Scheme 1. Scope of the Rh-Catalyzed Synthesis of
a b
,
Trisubstituted Allenes
a
b
entry
ligand
conversion (%)
es (%)
1
2
3
4
5
6
7
4
5
>95
46
98
98
c
(BnO) PN(iPr) (6)
<5
n.d.
2
2
7
>95
>95
>95
61
89
91
94
83
DPPF (8)
9
P(OMe) (10)
3
a
1
Determined by H NMR analysis of the crude reaction mixture.
b
Determined by supercritical fluid chromatography (SFC) on a chiral
c
stationary phase. Not determined.
substitution of the boronic acid was well tolerated (3b, 3e).
Although most substrates gave full conversion and good to
excellent yields using readily available [{Rh(cod)Cl} ] under
2
the conditions described above, we have found that the
addition of water generally led to an increase of the reaction
rate while the selectivity was slightly lowered. For example, full
conversion (96% yield) and 95% es were observed in the
synthesis of 3g when 10 equiv of water were added to the
reaction mixture. In the absence of added water, an allene
adduct was isolated in 79% yield and 99% es. We also noted
that the use of [{Rh(cod)OH} ] resulted in higher conversions
2
in certain cases.
In general, the substrates can be substituted with linear,
1
branched secondary or tertiary alkyl groups (R ) in α-position
to the propargylic benzoate. The reaction is slower with
increasing size of the substituent on the alkyne distal to the
2
benzoate (R ). The starting materials were cleanly recovered
2
for substrates with Me Si-substituted alkynes (R ). As a
3
limitation, strongly electron-poor arylboronic acids as well as
vinyl- and alkylboronic acids are not suitable coupling partners
at the current level of development. Preliminary experiments
revealed that the use of terminal alkynes in the reaction gave a
complex mixture of products, from which none could be
a
9
,10
Yields refer to isolated products after purification by chromatography
identified as being allenes.
b
on silica gel. Enantiomeric excesses were determined by supercritical
fluid chromatography (SFC) on a chiral stationary phase. Reaction
conducted at 40 °C for 12 h. 10 equiv of H
of H O were added, and [{Rh(cod)OH} ] (3 mol %) was used.
The structures of three allene products (3f−3h) were
c
confirmed by X-ray crystallographic analysis, and the absolute
d
e
11
2
O were added. 10 equiv
configuration for 3f was established accordingly. On the basis
of this configurational assignment, some insight can be gained
and a mechanism can be proposed. Hence, the reaction likely
proceeds through regioselective arylrhodation of the alkyne to
give an organorhodium intermediate (Scheme 2: 12 + 1 → 13)
followed by a selective syn-elimination to yield the observed
2
2
good yields and with high stereoselectivity (≥90% es). The
chiral propargylic alcohol derivatives employed are readily
accessible through enantioselective addition of alkynes to
aliphatic aldehydes or asymmetric ketone reductions. Thus, the
method allows the synthesis of enantioenriched allenes in a
convergent and stereoselective manner from simple precursors
under mild conditions and without the use of sensitive
organometallic reagents.
4
a,5a,12
allene.
An alternative mechanism proceeding through an
3a−c
allenyl-Rh intermediate cannot be excluded.
Interestingly,
no products from direct S 2 substitution were observed.
N
In conclusion, we have disclosed the first example of a Rh-
catalyzed, stereoselective synthesis of allenes from chiral
propargylic alcohol derivatives and arylboronic acids. This
method furnishes structurally diverse trisubstituted allenes in
B
DOI: 10.1021/acs.orglett.6b00793
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
see: (a) Yoshida, M.; Gotou, T.; Ihara, M. Tetrahedron Lett. 2004, 45,
Scheme 2. Mechanistic Proposal Accounting for the
5
573. (b) Molander, G. A.; Sommers, E. M.; Baker, S. R. J. Org. Chem.
2006, 71, 1563. (c) Yoshida, M.; Okada, T.; Shishido, K. Tetrahedron
007, 63, 6996. For Cu-catalyzed, stereoselective preparation of
Observed Absolute Configuration through cis-Addition and
5a
syn-Elimination
2
allenes from propargylic alcohol derivatives and boron nucleophiles,
see: (d) Ito, H.; Sasaki, Y.; Sawamura, M. J. Am. Chem. Soc. 2008, 130,
1
5774. (e) Yang, M.; Yokokawa, N.; Ohmiya, H.; Sawamura, M. Org.
Lett. 2012, 14, 816. For the synthesis of allenylsilanes, see: (f) Vyas,
D. J.; Hazra, C. K.; Oestreich, M. Org. Lett. 2011, 13, 4462. (g) Hazra,
C. K.; Oestreich, M. Org. Lett. 2012, 14, 4010. (h) Yokobori, U.;
Ohmiya, H.; Sawamura, M. Organometallics 2012, 31, 7909. For the
synthesis of alkyl substituted allenes utilizing alkylboron reagents, see:
(i) Ohmiya, H.; Yokobori, U.; Makida, Y.; Sawamura, M. Org. Lett.
2
011, 13, 6312. (j) Uehling, M. R.; Marionni, S. T.; Lalic, G. Org. Lett.
2
012, 14, 362.
(4) (a) Miura, T.; Shimada, M.; Ku, S.-Y.; Tamai, T.; Murakami, M.
Angew. Chem., Int. Ed. 2007, 46, 7101. For related studies to this work,
see: (b) Miura, T.; Shimada, M.; de Mendoza, P.; Deutsch, C.; Krause,
N.; Murakami, M. J. Org. Chem. 2009, 74, 6050. (c) Yoshida, M.;
Hayashi, M.; Matsuda, K.; Shishido, K. Heterocycles 2009, 77, 193. For
the Rh-catalyzed, stereospecific synthesis of allenylsilanes from
propargylic carbonates, see: (d) Ohmiya, H.; Ito, H.; Sawamura, M.
Org. Lett. 2009, 11, 5618. (e) For a Rh-catalyzed synthesis of
tetrasubstituted, chiral allenes, see ref 1j.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b00793.
(5) For an example where the stereoselectivity was found to be low
with propargylic alcohol derivatives under Rh-catalysis, see: (a) Mur-
akami, M.; Igawa, H. Helv. Chim. Acta 2002, 85, 4182. For a selected
Experimental procedures, characterization, and NMR
spectra for obtained compounds (PDF)
X-ray data for compound 3f (CIF)
X-ray data for compound 3h (CIF)
X-ray data for compound 3g (CIF)
example under Fe-catalysis, see: (b) Fu
Chem., Int. Ed. 2003, 42, 5355.
6) (a) Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem. Soc.
̈
́
rstner, A.; Mendez, M. Angew.
(
̈
2
000, 122, 1806. (b) Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc.
2
001, 123, 9687. (c) Takita, R.; Yakura, K.; Ohshima, T.; Shibasaki, M.
J. Am. Chem. Soc. 2005, 127, 13760. (d) Trost, B. M.; Weiss, A. H.;
Jacobi von Wangelin, A. J. Am. Chem. Soc. 2006, 128, 8. For a selected
review, see: (e) Trost, B. M.; Weiss, A. H. Adv. Synth. Catal. 2009, 351,
AUTHOR INFORMATION
Corresponding Author
■
*
9
(
63.
7) (a) Midland, M. M.; McDowell, D. C.; Hatch, R. L.; Tramontano,
A. J. Am. Chem. Soc. 1980, 102, 867. (b) Midland, M. M. Chem. Rev.
989, 89, 1553. (c) Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori,
E-mail: carreira@org.chem.ethz.ch.
Notes
1
The authors declare no competing financial interest.
R. J. Am. Chem. Soc. 1997, 119, 8738. (d) Corey, E. J.; Helal, C. J.
Angew. Chem., Int. Ed. 1998, 37, 1986.
ACKNOWLEDGMENTS
We are grateful to Dr. N. Trapp (ETH Zu
■
(
(8) (a) Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew.
Chem., Int. Ed. 2007, 46, 3139. For the use of a phosphine olefin
phosphoramidite ligand in a Rh-catalyzed enantioselective intra-
molecular hydroacylation reaction, see: (b) Hoffman, T. J.; Carreira,
E. M. Angew. Chem., Int. Ed. 2011, 50, 10670.
̈
rich) and M. Solar
ETH Zu
̈
rich) for X-ray crystallographic analyses. We thank the
Swiss National Science Foundation for support of this work
through Grant SNF 152898.
(
9) For a Rh-catalyzed propargylic amination reaction of terminal
alkynes, see: Evans, P. A.; Lawler, M. J. Angew. Chem., Int. Ed. 2006, 45,
970.
10) For selected, recent work employing allenes as starting materials
REFERENCES
■
4
(
1) (a) Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.;
(
Wiley-VCH: Weinheim, 2004; Vols. 1 and 2. (b) Marshall, J. A. Chem.
Rev. 2000, 100, 3163. (c) Zimmer, R.; Dinesh, C. U.; Nandanan, E.;
Khan, F. A. Chem. Rev. 2000, 100, 3067. (d) Ma, S. Chem. Rev. 2005,
I
under Rh -catalysis, see: (a) Kawamoto, T.; Hirabayashi, S.; Guo, X.-
X.; Nishimura, T.; Hayashi, T. Chem. Commun. 2009, 3528.
(b) Koschker, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011,
1
05, 2829. (e) Ma, S. Acc. Chem. Res. 2009, 42, 1679. (f) Krause, N.;
1
2
33, 20746. (c) Cooke, M. L.; Xu, K.; Breit, B. Angew. Chem., Int. Ed.
012, 51, 10876. (d) Xu, K.; Thieme, N.; Breit, B. Angew. Chem., Int.
Winter, C. Chem. Rev. 2011, 111, 1994. (g) Yu, S.; Ma, S. Angew.
Chem., Int. Ed. 2012, 51, 3074. (h) Grillet, F.; Brummond, K. M. J. Org.
Chem. 2013, 78, 3737. (i) Neff, R. K.; Frantz, D. E. Tetrahedron 2015,
Ed. 2014, 53, 2162. (e) Xu, K.; Thieme, N.; Breit, B. Angew. Chem., Int.
Ed. 2014, 53, 7268. (f) Li, C.; Breit, B. J. Am. Chem. Soc. 2014, 136,
7
1, 7. (j) Wu, S.; Huang, X.; Wu, W.; Li, P.; Fu, C.; Ma, S. Nat.
Commun. 2015, 6, 7946.
2) For selected reviews on the synthesis of allenes, see:
a) Hoffmann-Roder, A.; Krause, N. Angew. Chem., Int. Ed. 2004,
3, 1196. (b) Brummond, K. M.; DeForrest, J. E. Synthesis 2007, 2007,
95. (c) Yu, S.; Ma, S. Chem. Commun. 2011, 47, 5384. (d) Neff, R. K.;
8
1
3
5
̈
62. (g) Li, C.; Kahny, M.; Breit, B. Angew. Chem., Int. Ed. 2014, 53,
3780. (h) Pritzius, A. B.; Breit, B. Angew. Chem., Int. Ed. 2015, 54,
121. (i) Haydl, A. M.; Xu, K.; Breit, B. Angew. Chem., Int. Ed. 2015,
4, 7149. (j) See also ref 1h and references therein.
(
(
4
̈
(11) CCDC 1437268 (3f), 1446561 (3g), and 1437269 (3h) contain
7
the supplementary crystallographic data for this publication. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
Frantz, D. E. ACS Catal. 2014, 4, 519. (e) Ye, J.; Ma, S. Org. Chem.
Front. 2014, 1, 1210. For a recent review covering the transition-
metal-catalyzed, enantioselective and enantiospecific synthesis of
allenes from organometallic reagents, see: (f) Cherney, A. H.;
Kadunce, N. T.; Reisman, S. E. Chem. Rev. 2015, 115, 9587.
(12) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem. Soc. 2007,
1
29, 1876.
(
3) For Pd-catalyzed, stereoselective synthesis of allenes from
propargylic alcohol derivatives and aryl- or alkenylboron compounds,
C
DOI: 10.1021/acs.orglett.6b00793
Org. Lett. XXXX, XXX, XXX−XXX