Ni-Catalyzed β-Alkylation of Cyclopropanol-Derived Homoenolates

Article abstract of DOI:10.1021/acs.orglett.9b03435

Metal homoenolates are valuable synthetic intermediates which provide access to β-functionalized ketones. In this report, we disclose a Ni-catalyzed β-alkylation reaction of cyclopropanol-derived homoenolates using redox-active N-hydroxyphthalimide (NHPI) esters as the alkylating reagents. The reaction is compatible with 1°, 2°, and 3° NHPI esters. Mechanistic studies imply radical activation of the NHPI ester and 2e β-carbon elimination occurring on the cyclopropanol.

Full text of DOI:10.1021/acs.orglett.9b03435

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Ni-Catalyzed β‑Alkylation of Cyclopropanol-Derived Homoenolates
L. Reginald Mills, Cuihan Zhou,† Emily Fung, and Sophie A. L. Rousseaux*
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6,
Canada
S
* Supporting Information
ABSTRACT: Metal homoenolates are valuable synthetic inter-
mediates which provide access to β-functionalized ketones. In this
report, we disclose a Ni-catalyzed β-alkylation reaction of
cyclopropanol-derived homoenolates using redox-active N-hydrox-
yphthalimide (NHPI) esters as the alkylating reagents. The reaction
is compatible with 1°, 2°, and 3° NHPI esters. Mechanistic studies
imply radical activation of the NHPI ester and 2e β-carbon
elimination occurring on the cyclopropanol.
he chemistry of metal homoenolates has a rich history,1
Scheme 1. β-Functionalization and β-Alkylation of
Cyclopropanol-Derived Homoenolates
Tand recent years have seen a resurgence of transition-
metal-catalyzed transformations of homoenolates.2,3 The metal
homoenolate is an interesting synthetic intermediate since it
exhibits umpolung reactivity that can be exploited for facile,
selective β-functionalization of carbonyl derivatives with
electrophiles. Cyclopropanols are ideal metal homoenolate
precursors since they are bench stable and can be readily
accessed in a few steps from inexpensive starting materials.2,4 A
number of methods have now been reported for the coupling
of various functional groups with cyclopropanol-derived
homoenolates.2−4 For β-carbon−carbon bond-forming reac-
tions, the most versatile metals are Pd, Cu, Rh, and Co, and
arylation, alkenylation, alkynylation, and allenylation methods
using these metals have been reported (Scheme 1a).2,3,5
Notably, the most common of these transition-metal-catalyzed
protocols are those entailing the installation of C(sp2) or
C(sp) functional groups, and protocols which achieve β-
alkylation of cyclopropanol-derived homoenolates are limited.
It is recognized that nonplanar motifs are desirable in drug
discovery, and there is a desire for the synthesis of C(sp3)-rich
molecules which can help “escape the flatland”.6 In this vein,
the C-alkylation of cyclopropanol-derived homoenolates
represents an interesting strategy for the synthesis of β-alkyl
ketones. While selected examples of β-alkylation of cyclo-
propanol-derived homoenolates have been reported, these
protocols are currently only applicable to specific substrate
classes (Scheme 1b). Matsubara and co-workers reported the
Cu-catalyzed allylation of Zn cyclopropoxides,7 and in 2012,
Cha and co-workers reported a similar strategy for the
allylation and propargylation of cyclopropanols.8 In 2015,
Dai and co-workers showed that α-bromocarbonyls are also
viable alkylating reagents under Cu catalysis.9 While these
protocols are convenient, they are restricted to specific
substrate classes, and to date, a strategy for β-alkylation of
cyclopropanols with a broad range of alkyl electrophiles has
not been reported.10−12
Inspired by recent work on Ni-catalyzed reactions of redox-
active N-hydroxyphthalimide (NHPI) esters reported by the
groups of Baran13 and Weix,14 we wondered if NHPI esters
Received: September 27, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03435
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
could be used for the β-alkylation of cyclopropanol-derived Ni
homoenolates. This C(sp3)−C(sp3) cross-coupling would be
inherently challenging due to the propensity of the C(sp3)
coupling partners to undergo β-hydride elimination and
protodemetalation.15 As alkylating reagents, NHPI esters are
advantageous since they are readily prepared from abundant
carboxylic acids, are easy to handle, and possess low toxicity in
comparison to their alkyl halide counterparts.16
Herein, we report a Ni-catalyzed β-alkylation of cyclo-
propanol-derived homoenolates using NHPI esters (Scheme
1c). This methodology is viable for 1°, 2°, and 3° NHPI esters,
tolerates a number of functional groups, and can be applied to
the late-stage functionalization of medicinally relevant
substrates. There are limited reports on the chemistry of Ni
homoenolates,17 and this procedure represents one of the first
instances of a reaction employing cyclopropanol-derived Ni
homoenolates.3
competent (Table S1). Pretreating 1a with a strong base like
NaH (3 equiv) or Et2Zn (1.5 equiv) to generate the
cyclopropoxide salt in situ resulted in very low yields of 3a
(entries 5 and 6), suggesting that preformation of a metal
cyclopropoxide or metal homoenolate is not productive for this
reaction. For these reactions, a significant side product was the
ester resulting from transesterification of 2a with 1a.18 Though
some product was formed in the absence of ZnCl2 (40%, entry
8), ZnCl2 was ultimately necessary for optimal yields, and the
use of other Lewis acids (MgCl2, entry 7; see also Table S1)
did not give comparable yields. The role of ZnCl2 is currently
unclear, though we believe it may act as a Lewis acid to help
activate 2 and stabilize the radical anion intermediate
generated after reduction of 2.19 Finally, performing the
reaction in the absence of a Ni catalyst (entry 9) resulted in no
detectable yield of 3a.
A particular challenge in the development of this reaction is
the propensity of 1a to undergo rapid ring-opening isomer-
ization to the ketone (i.e., propiophenone),20 which occurs at
temperatures as low as rt and which is mediated efficiently by
ZnCl2 at 120 °C (see Table S7 for details). The rapid
isomerization of 1a under the reaction conditions is the
primary reason for requiring an excess of 1a. This isomer-
ization represents a formal migration of the alcohol proton on
1a; however, strategies for eliminating the proton, such as
stoichiometric deprotonation (entries 5 and 6), or using a
TMS-protected cyclopropanol (Table S4),21 were not
successful. Preliminary kinetic analysis is consistent with
isomerization of 1a on the time scale of formation of 3a,
suggesting that these pathways are competitive. Thus, one
reason for this reaction’s high temperature may be to promote
productive intermolecular coupling (see Table S3 for temper-
ature data). It is also worth noting that the reaction of 1a and
2a under standard conditions is complete within 5 min.22 For
the same reaction using 1-benzylcyclopropanol instead of 1a,
the reaction is complete within 30 min.
The optimal conditions for the β-alkylation of cyclo-
propanol-derived homoenolates are shown in Table 1. Using
a
Table 1. Optimization of the Reaction
b
entry
deviation from std cond
yield of 3a (%)
c
1
2
3
4
none
85
using NiCl2(bpy) (10 mol %)
using NiCl2(dtbbpy) (10 mol %)
without NEt3
NaH (3 equiv) instead of NEt3
Et2Zn (1.5 equiv) instead of NEt3
MgCl2 instead of ZnCl2
without ZnCl2
81
54
3
d
5
6
0
d
20
12
40
0
7
8
9
A summary of β-functionalized ketones that have been
prepared using this protocol is shown in Table 2. The reaction
is tolerant of 1-arylcyclopropanols with various substituents,
including electron-rich (3b, 3c, 3j, 3k, 3l) and electron-neutral
(3d) substituents as well as a 1-heteroarylcyclopropanol (3f).
1-Alkyl-substituted cyclopropanols are competent substrates as
well (3g, 3h, 3i, 3s), though they react more efficiently in
DMA than DMF (see Table S4). Cyclopropanol derivatives
with substituents at C2 and C3 were generally not competent
under the current conditions (Table S6). In terms of
compatible NHPI esters, 2° esters with various steric
properties (3a, 3k, 3l) are compatible coupling partners, as
are 1° alkyl esters (3j, 3r−3u), 1° benzylic esters (3v), and 3°
esters (3n). The α-amino NHPI ester derived from N-Boc
proline (3d−3e, 3h−3i, 3m) was also compatible; the
corresponding alkyl halide coupling partner would be
challenging to prepare and handle, clearly highlighting an
advantage of using NHPI esters in this cross-coupling protocol.
The reaction is tolerant of various functional groups including
carbamate (3m, 3p), urea (3o), amide (3q), ester and alkene
(3u), and aryl chloride (3v). The use of complex substrates 3j,
3t−3v demonstrates how this protocol might be applicable to
late-stage β-alkylation in the context of complex target
synthesis.23 For some substrates, it was also found that
NiCl2(dtbbpy) outperformed NiCl2(phen); it appears that
NiCl2(dtbbpy) may be the more suitable catalyst for reactions
of 1° NHPI esters (3r) or for substrates bearing Lewis basic
without NiCl2(phen)
a
Reaction conditions: cyclopropanol 1a (40 mg, 0.30 mmol), ester
2a (27 mg, 0.10 mmol), NiCl2(phen) (3.1 mg, 0.010 mmol), ZnCl2
(27 mg, 0.20 mmol), NEt3 (28 μL, 0.20 mmol), DMF (0.50 mL), 120
°C, 1 h. GC−MS yields based on n-dodecane as internal standard.
Average of three runs. Base was prestirred with cyclopropanol 1a for
5 min at rt in DMF before combining with the other reaction
components. dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl; NHPI = N-
hydroxyphthalimide; phen = 1,10-phenanthroline.
b
c
d
1-phenylcyclopropanol (1a) and redox-active N-hydroxyph-
thalimide ester 2a as model substrates, the desired β-
alkylketone product 3a could be formed in 85% yield in the
presence of NiCl2(phen) (10 mol %), triethylamine (2 equiv),
and ZnCl2 (2 equiv) in DMF at 120 °C after 1 h. While
NiCl2(phen) was determined to be the most optimal and
general precatalyst, a number of other precatalyst/ligand
combinations delivered 3a in practical yields (e.g., NiCl2(bpy)
or NiCl2(dtbbpy), entries 2 and 3; see also Table S2).
Triethylamine (2 equiv) was vital for the success of the
reaction; performing the reaction without triethylamine gave
only 3% yield of 3a (entry 4). Other weak bases were less
B
DOI: 10.1021/acs.orglett.9b03435
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 2. Scope of the reaction
a
b
Reactions performed on 0.20−0.30 mmol scale. Yields are for isolated material; Performed in duplicate; displayed yield is the average of two
c
d
runs. Using DMA (0.20 M) instead of DMF. Using NiCl2(dtbbpy) (10 mol %); see the Supporting Information for yields using NiCl2(phen);
e
Performed on 0.10 mmol scale. dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl; NHPI = N-hydroxyphthalimide. For supplementary examples see SI
(Table S5).
functional groups (3i, 3q) (see the Supporting Information for
details).
electron) mechanisms.24,25 When bicyclic cyclopropanol 1b
was treated with 2a under standard conditions, product 3w was
isolated in 13% yield. Product 3w was the only detectable β-
alkylketone isomer by GC−MS, which is consistent with a two-
electron β-carbon elimination pathway. The remaining mass
balance of 1b in this reaction went to the ring-opened isomer.
A likely mechanism for this transformation is shown in
Scheme 3. Starting with the Ni(II) precatalyst, catalyst
activation may occur via disproportionation to generate
Ni(I)−X species 6.26 From 6, ligand exchange with 1 and
deprotonation by Et3N can form Ni(I) cyclopropoxide 7.
Cyclopropoxide 7 is in equilibrium with Ni(I) homoenolate 8,
though it is presently unknown to which side this equilibrium
lies.27,28 Then single-electron transfer (SET) to NHPI ester 2,
followed by fragmentation and recombination, generates
Ni(III) homoenolate 9. Finally, reductive elimination releases
Experiments that were performed to better understand the
reaction mechanism are shown in Scheme 2. When
enantiopure NHPI ester 2b was exposed to the reaction
conditions, complete loss of stereochemical information was
observed (Scheme 2a). Also, when alkene-containing substrate
4 was employed in a standard reaction with 1a, 35% of the 5-
exo-trig-cyclized product 5 was observed (Scheme 2b), with
>20:1 selectivity for 5 over the corresponding uncyclized
alkene. These results are consistent with the generation of
radical intermediates from the NHPI ester starting material.
Next, bicyclic cyclopropanol 1b was exposed to the reaction
conditions. Bicyclic cyclopropanol derivatives are known to
undergo exocyclic ring-opening under polar (two-electron)
mechanisms2 and endocyclic ring-opening via radical (one-
C
DOI: 10.1021/acs.orglett.9b03435
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
we anticipate many interesting opportunities for reaction
development exploiting these intermediates.
Scheme 2. Mechanistic Experiments
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03435.
Reaction optimization tables, mechanistic studies,
synthetic procedures, and characterization data (PDF)
NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: sophie.rousseaux@utoronto.ca.
ORCID
Sophie A. L. Rousseaux: 0000-0002-6505-5593
Present Address
†(C.Z.) Department of Chemistry, McGill University, 801
a
See the Supporting Information for full experimental details.
́
Sherbrooke St. West, Montreal, QC H3A 0B8, Canada.
Scheme 3. Proposed Catalytic Cycle
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank NSERC (Discovery Grants and Canada Research
Chair programs), the Canada Foundation for Innovation
(Project No. 35261), the Ontario Research Fund, and the
University of Toronto for generous financial support of this
work. We also acknowledge the Canada Foundation for
Innovation (Project No. 19119) and the Ontario Research
Fund for funding the Centre for Spectroscopic Investigation of
Complex Organic Molecules and Polymers. L.R.M. thanks
NSERC for a graduate scholarship (PGS D). Tylor McDonald
(University of Toronto) is thanked for comments in the
preparation of this manuscript. Nicholas Michel (University of
Toronto) is thanked for the synthesis of starting material S19.
REFERENCES
■
(1) (a) Nakamura, E.; Aoki, S.; Sekiya, K.; Oshino, H.; Kuwajima, I.
Carbon-carbon bond-forming reactions of zinc homoenolate of esters.
A novel three-carbon nucleophile with general synthetic utility. J. Am.
Chem. Soc. 1987, 109, 8056−8066. (b) Kuwajima, E.; Nakamura, E.
Metal Homoenolates from Siloxycyclopropanes. Top. Curr. Chem.
1990, 155, 1−39. (c) Crimmins, M. T.; Nantermet, P. G.
Homoenolates and Other Functionalized Organometallics. A Review.
Org. Prep. Proced. Int. 1993, 25, 41−81.
desired product 3 and regenerates Ni(I) species 6. It is possible
that ZnCl2 helps form cyclopropoxide or homoenolate
intermediates from 1, which could be beneficial for the ligand
exchange (or transmetalation) steps.8 However, since the
reaction also proceeds in the absence of ZnCl2 (Table 1, entry
8), and since a preformed Zn homoenolate is not a competent
intermediate (Table 1, entries 5 and 6), we believe
homoenolate formation occurs predominantly on the Ni
center.
In conclusion, we have developed a Ni-catalyzed protocol
for the β-alkylation of cyclopropanol-derived homoenolates
using redox-active NHPI esters. Using this method, a variety of
β-alkyl ketones can be prepared. There is a very limited
number of reports on the chemistry of Ni homoenolates, and
(2) Mills, L. R.; Rousseaux, S. A. L. Modern Developments in the
Chemistry of Homoenolates. Eur. J. Org. Chem. 2019, 2019, 8−26.
(3) Nikolaev, A.; Orellana, A. Transition-Metal-Catalyzed C−C and
C−X Bond-Forming Reactions Using Cyclopropanols. Synthesis 2016,
48, 1741−1768.
(4) Kulinkovich, O. G. The Chemistry of Cyclopropanols. Chem.
Rev. 2003, 103, 2597−2632.
(5) For a recent example of a C(sp3)−C(sp2) bond-forming reaction
using Co, see: Yang, J.; Sun, Q.; Yoshikai, N. Cobalt-Catalyzed Regio-
and Diastereoselective Formal [3 + 2] Cycloaddition between
Cyclopropanols and Allenes. ACS Catal. 2019, 9, 1973−1978.
(6) Lovering, F.; Bikker, J.; Humblet, C. Escape from Flatland:
Increasing Saturation as an Approach to Improving Clinical Success. J.
Med. Chem. 2009, 52, 6752−6756.
D
DOI: 10.1021/acs.orglett.9b03435
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(7) Nomura, K.; Matsubara, S. Preparation of Zinc−Homoenolate
from α-Sulfonyloxy Ketone and Bis(iodozincio)methane. Chem. Lett.
2007, 36, 164−165.
catalyzed cyclopropanol ring-opening reaction. Tetrahedron Lett.
2010, 51, 6726−6729.
(21) Rosa, D.; Orellana, A. Palladium-Catalyzed Cross-Coupling of
Cyclopropanols with Aryl Halides Under Mild Conditions. Org. Lett.
2011, 13, 110−113.
(8) Das, P. P.; Belmore, K.; Cha, J. K. SN2′ Alkylation of
Cyclopropanols via Homoenolates. Angew. Chem., Int. Ed. 2012, 51,
9517−9520.
(22) This is consistent with reaction times observed in other
couplings of redox-active N-hydroxyphthalimide esters: Toriyama, F.;
Cornella, J.; Wimmer, L.; Chen, T.-G.; Dixon, D. D.; Creech, G.;
Baran, P. S. Redox-Active Esters in Fe-Catalyzed C−C Coupling. J.
Am. Chem. Soc. 2016, 138, 11132−11135.
(23) Product 3j can be demethylated to arrive at the natural product
in one step: Kundu, K.; Nayak, S. K. Total Syntheses of
Malabaricones B and C via a Cross-Metathesis Strategy. J. Nat.
Prod. 2017, 80, 1776−1782.
(24) For pioneering references, see: (a) DePuy, C. H.; Van Lanen,
R. J. Reactions of Cyclopropanols with Halogenating Agents and
Other Electrophiles. J. Org. Chem. 1974, 39, 3360−3365. (b) Ito, Y.;
Fujii, S.; Saegusa, T. Reaction of 1-Silyloxybicyclo[n.1.0]alkanes with
FeIIICl3. A Facile Synthesis of 2-Cycloalkenones via Ring Enlargement
of Cyclic Ketones. J. Org. Chem. 1976, 41, 2073−2074.
(25) Burdge, H. E.; Oguma, T.; Kawajiri, T.; Shenvi, R. A. Concise
synthesis of GB22 by endo-selective siloxycyclopropane arylation.
ChemRxiv 2019, DOI: 10.26434/chemrxiv.8263415.v1.
(9) (a) Ye, Z.; Gettys, K. E.; Shen, X.; Dai, M. Copper-Catalyzed
Cyclopropanol Ring Opening Csp3−Csp3 Cross-Couplings with
(Fluoro)Alkyl Halides. Org. Lett. 2015, 17, 6074−6077. (b) Ye, Z.;
Cai, X.; Li, J.; Dai, M. Catalytic Cyclopropanol Ring Opening for
Divergent Syntheses of γ-Butyrolactones and δ-Ketoesters Containing
All-Carbon Quaternary Centers. ACS Catal. 2018, 8, 5907−5914.
(10) For β-installation of fluoroalkyl substituents, see: (a) Li, Y.; Ye,
Z.; Bellman, T. M.; Chi, T.; Dai, M. Efficient Synthesis of β-CF3/
SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-
Opening Cross-Coupling of Cyclopropanols. Org. Lett. 2015, 17,
2186−2189. (b) Kananovich, D. G.; Konik, Y. A.; Zubrytski, D. M.;
̈
Jarving, I.; Lopp, M. Simple access to β-trifluoromethyl-substituted
ketones via copper-catalyzed ring-opening trifluoromethylation of
substituted cyclopropanols. Chem. Commun. 2015, 51, 8349−8352.
(c) He, X.-P.; Shu, Y.-J.; Dai, J.-J.; Zhang, W. M.; Feng, Y. S.; Xu, H. J.
Copper-catalysed ring-opening trifluoromethylation of cyclopropa-
nols. Org. Biomol. Chem. 2015, 13, 7159−7163. (d) Konik, Y. A.;
(26) Ni, S.; Padial, N. M.; Kingston, C.; Vantourout, J. C.; Schmitt,
D. C.; Edwards, J. T.; Kruszyk, M. M.; Merchant, R. R.; Mykhailiuk, P.
K.; Sanchez, B. B.; Yang, S.; Perry, M. A.; Gallego, G. M.; Mousseau, J.
J.; Collins, M. R.; Cherney, R. J.; Lebed, P. S.; Chen, J. S.; Qin, T.;
Baran, P. S. A Radical Approach to Anionic Chemistry: Synthesis of
Ketones, Alcohols, and Amines. J. Am. Chem. Soc. 2019, 141, 6726−
6739.
̈
Kudrjashova, M.; Konrad, N.; Kaabel, S.; Jarving, I.; Lopp, M.;
Kananovich, D. G. Two-step conversion of carboxylic esters into
distally fluorinated ketones via ring cleavage of cyclopropanol
intermediates: application of sulfinate salts as fluoroalkylating
reagents. Org. Biomol. Chem. 2017, 15, 4635−4643.
(11) For an example of Pd-catalyzed benzylation of cyclopropanol-
derived homoenolates, see: Nithiy, N.; Orellana, A. Palladium-
Catalyzed Cross-Coupling of Benzyl Chlorides with Cyclopropanol-
Derived Ketone Homoenolates. Org. Lett. 2014, 16, 5854−5857.
(12) For a report on the Co-catalyzed hydroalkylation of oxabicyclic
alkenes, see: Yang, J.; Sekiguchi, Y.; Yoshikai, N. Cobalt-Catalyzed
Enantioselective and Chemodivergent Addition of Cyclopropanols to
Oxabicyclic Alkenes. ACS Catal. 2019, 9, 5638−5644.
(13) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.;
Pan, C.-M.; Gianatassio, R.; Schmidt, M.; Eastgate, M. D.; Baran, P. S.
Practical Ni-Catalyzed Aryl−Alkyl Cross-Coupling of Secondary
Redox-Active Esters. J. Am. Chem. Soc. 2016, 138, 2174−2177.
(14) Huihui, K. M. M.; Caputo, J. A.; Melchor, Z.; Olivares, A. M.;
Spiewak, A. M.; Johnson, K. A.; DiBenedetto, T. A.; Kim, S.;
Ackerman, L. K. G.; Weix, D. J. Decarboxylative Cross-Electrophile
Coupling of N-Hydroxyphthalimide Esters with Aryl Iodides. J. Am.
Chem. Soc. 2016, 138, 5016−5019.
(27) Park, S.-B.; Cha, J. K. Palladium-Mediated Ring Opening of
Hydroxycyclopropanes. Org. Lett. 2000, 2, 147−149.
(28) The “transmetalation-first” pathway proposed here is informed
by typical reaction mechanisms for Ni(I)/Ni(III) catalytic cycles,
though it is also possible that ligand exchange occurs after oxidative
addition. We favor the pathway proposed for two empirical reasons:
(1) side products arising from side reactions of the NHPI ester
(reduced and homocoupled dimer side products) have been virtually
undetected in this reaction, suggesting that 2 is consumed at a stage in
the catalytic cycle where product formation is possible and facile; (2)
unproductive protodemetalation from a homoenolate intermediate
such as 8 seems likely in the case where the Ni catalyst has interacted
with 1 but not 2, i.e., where product formation is not facile, and this
unproductive pathway can explain the major ring-opened side product
in this reaction.
(15) Qin, T.; Cornella, J.; Li, C.; Malins, L. R.; Edwards, J. T.;
Kawamura, S.; Maxwell, B. D.; Eastgate, M. D.; Baran, P. S. A general
alkyl-alkyl cross-coupling enabled by redox- active esters and alkylzinc
reagents. Science 2016, 352, 801−805. See also references cited
therein.
(16) For a review, see: Murarka, S. N-(Acyloxy)phthalimides as
Redox-Active Esters in Cross-Coupling Reactions. Adv. Synth. Catal.
2018, 360, 1735−1753.
(17) For examples of Ni-catalyzed Negishi reactions of preformed
Zn homoenolates, see: (a) Reference 1a. (b) Rogers, R. L.; Moore, J.
L.; Rovis, T. Alkene-Directed Regioselective Nickel-Catalyzed Cross-
Coupling of Cyclic Anhydrides with Diorganozinc Reagents. Angew.
Chem., Int. Ed. 2007, 46, 9301−9304.
(18) Parida, B. B.; Das, P. P.; Niocel, M.; Cha, J. K. C-Acylation of
Cyclopropanols: Preparation of Functionalized 1,4-Diketones. Org.
Lett. 2013, 15, 1780−1783.
(19) Zhang, J.-J.; Yang, J.-C.; Guo, L.-N.; Duan, X.-H. Visible-Light-
Mediated Dual Decarboxylative Coupling of Redox-Active Esters with
α,β-Unsaturated Carboxylic Acids. Chem. - Eur. J. 2017, 23, 10259−
10263.
(20) (a) Hoberg, J. O.; Jennings, P. W. Platinum(II)-Catalyzed
Isomerization of Alkoxycyclopropanes to Alkylated Ketones. Organo-
metallics 1996, 15, 3902−3904. (b) Ziegler, D. T.; Steffens, A. M.;
Funk, T. W. Synthesis of α-methyl ketones by a selective, iridium-
E
DOI: 10.1021/acs.orglett.9b03435
Org. Lett. XXXX, XXX, XXX−XXX