Shuttle arylation by Rh(I) catalyzed reversible carbon–carbon bond activation of unstrained alcohols

Article abstract of DOI:10.1016/j.chempr.2021.02.029

The advent of transfer hydrogenation and borrowing hydrogen reactions paved the way to manipulate simple alcohols in previously unthinkable manners and circumvented the need for hydrogen gas. Analogously, transfer hydrocarbylation could greatly increase the versatility of tertiary alcohols. However, this reaction remains unexplored because of the challenges associated with the catalytic cleavage of unactivated C–C bonds. Herein, we report a rhodium(I)-catalyzed shuttle arylation cleaving the C(sp²)–C(sp³) bond in unstrained triaryl alcohols via a redox-neutral β-carbon elimination mechanism. A selective transfer hydrocarbylation of substituted (hetero)aryl groups from tertiary alcohols to ketones was realized, employing benign alcohols as latent C-nucleophiles. All preliminary mechanistic experiments support a reversible β-carbon elimination/migratory insertion mechanism. In a broader context, this novel reactivity offers a new platform for the manipulation of tertiary alcohols in catalysis.

Full text of DOI:10.1016/j.chempr.2021.02.029

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Article
Shuttle arylation by Rh(I) catalyzed reversible
carbon–carbon bond activation of unstrained
alcohols
Marius D.R. Lutz, Valentina C.M.
Gasser, Bill Morandi
bill.morandi@org.chem.ethz.ch
Highlights
Catalytic transfer arylation
paralleling transfer hydrogenation
Cleavage of strong C(sp2)–C(sp3)
bonds in unreactive alcohols
Mild access to 3ꢀ alcohols
avoiding Grignard and
organolithium reagents
Mechanistic experiments support
reversible b-carbon elimination/
insertion pathway
Carbon–carbon bonds are among the most abundant yet least reactive
functionalities in organic molecules. Here, we report a shuttle catalysis approach to
interconvert tertiary alcohols and ketones by reversibly cleaving and reforming
nonpolar C–C bonds without relying on a directing group. Preliminary mechanistic
experiments support a reversible bÀcarbon elimination/insertion mechanism. This
work lays the groundwork for creative ways to employ tertiary alcohols in synthesis,
paralleling advances made in transfer hydrogenation reactions.
Lutz et al., Chem 7, 1108–1119
April 8, 2021 ª 2021 Elsevier Inc.
https://doi.org/10.1016/j.chempr.2021.02.029

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Shuttle arylation by Rh(I) catalyzed
reversible carbon–carbon bond
activation of unstrained alcohols
Marius D.R. Lutz,1 Valentina C.M. Gasser,1 and Bill Morandi1,2,
*
SUMMARY
The bigger picture
Carbon–carbon bonds are
omnipresent in chemicals
The advent of transfer hydrogenation and borrowing hydrogen reac-
tions paved the way to manipulate simple alcohols in previously un-
thinkable manners and circumvented the need for hydrogen gas.
Analogously, transfer hydrocarbylation could greatly increase the
versatility of tertiary alcohols. However, this reaction remains unex-
plored because of the challenges associated with the catalytic cleav-
age of unactivated C–C bonds. Herein, we report a rhodium(I)-cata-
lyzed shuttle arylation cleaving the C(sp2)–C(sp3) bond in unstrained
triaryl alcohols via a redox-neutral b-carbon elimination mechanism.
A selective transfer hydrocarbylation of substituted (hetero)aryl
groups from tertiary alcohols to ketones was realized, employing
benign alcohols as latent C-nucleophiles. All preliminary mechanistic
experiments support a reversible b-carbon elimination/migratory
insertion mechanism. In a broader context, this novel reactivity offers
a new platform for the manipulation of tertiary alcohols in catalysis.
encountered in everyday life,
including biomolecules, many
polymers, and pharmaceuticals.
To enable the valorization of
renewable feedstocks and
recycling of industrially relevant
polymers, these stable C–C bonds
have to be selectively cleaved,
which remains a challenge in the
field of synthetic organic
chemistry. Previous methods have
limited applicability and rely on
substrate bias.
In this work, we describe a
reversible transfer
INTRODUCTION
Catalytic reversible reactions have found widespread use in the chemical community,
as highlighted by the broad range of applications that alkene metathesis offers across
the molecular sciences.1–4 Another prominent example is the transfer hydrogenation
reaction, in which secondary alcohols and ketones are interconverted by formally
shuttling a molecule of hydrogen, in lieu of using the hazardous gas (Scheme 1A,
top).5 Many variants of this concept have been developed over the years, including
borrowing hydrogen reactions that transiently dehydrogenate alcohols to construct
new C–C bonds.6–11 The analogous transfer hydrocarbylation reaction using tertiary
alcohols would provide exciting new avenues for the synthesis and modification of
these species; however, reversibly cleaving and reforming a strong C–C bond repre-
sents a far more considerable challenge (Scheme 1A, bottom).
hydrocarbylation reaction to
interconvert alcohols and ketones
by cleaving and reforming strong
C–C bonds. Using this method,
benign alcohols can serve as
alternatives to stoichiometric and
highly reactive organometallic
reagents to form value-added
alcohol products from ketones.
The work described herein
represents a step toward
valorizing renewable alcohols and
paves the way to develop a
platform for the creative
Methods to directly activate C–C bonds are attractive, as the substrates of interest
can be functionalized without the need to introduce reactive functional handles,
such as halides, and some have been strategically used in total synthesis.12 When
compared with the significant progress made in the functionalization of inert C–H
bonds, catalytic reactions to cleave strong C–C bonds selectively are scarce.13,14
Reasons for their low reactivity compared with C–H bonds can be found in their ki-
netic inertness, as the s-orbital is highly directional and does not allow for significant
overlap with the d-orbitals of transition metals.15,16
manipulation of tertiary alcohols
in catalysis.
Recently, several strategies to oxidatively cleave unstrained C–C bonds using di-
recting groups have been devised,14,15,17–20 however, there are few reports of
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Scheme 1. Context of this work
(A) Transfer hydrogenation is a widely employed reaction to interconvert 1ꢀ and 2ꢀ alcohols and carbonyl compounds. An analogous transfer
hydrocarbylation of 3ꢀ alcohols is unknown.
(B) Two main challenges, namely activation of the C(sp2)–C(sp3) bond in the alcohol and productive insertion of the ketone, have to be overcome to
unlock the desired reactivity.
(C) This work: development of a catalytic shuttle arylation reaction between 3ꢀ alcohols and ketones.
unbiased systems that proceed via redox-neutral b-carbon elimination.16,18,21,22
While strategies to activate propargylic and allylic alcohols are well known, the
activation of an unstrained C(sp2)–C(sp3) bond remains challenging. We and others
1Laboratory of Organic Chemistry, Department of
Chemistry and Applied Biosciences, ETH Zurich,
¨
have reported cross-couplings of a,a-disubstituted arylmethanols with alkene elec-
trophiles via directed C–C bond activation forging new C–C bonds.23–28 Despite
these, reports of selective C(sp2)–C(sp3) bond cleavage of alcohols without using
a directing group are rare and limited to specific substrate scaffolds designed
to relieve internal strain or gain aromaticity.29,30 A notable exception is a
Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland
¨
2Lead contact
*Correspondence:
bill.morandi@org.chem.ethz.ch
https://doi.org/10.1016/j.chempr.2021.02.029
Chem 7, 1108–1119, April 8, 2021 1109

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Pd-catalyzed biaryl coupling of a,a-disubstituted arylmethanols and aryl bromides
reported by Miura.31,32
Continuing our interest in developing catalytic reversible reactions,33–37 we sought
to develop a shuttle catalysis reaction to interconvert tertiary alcohols and ketones
via reversible C–C bond cleavage (Scheme 1A, bottom). Such a reaction would par-
allel the widely employed transfer hydrogenation reaction between alcohols and ke-
tones, with the key difference being that a C–C bond would be cleaved and
reformed instead of a C–H bond.
Besides the inherent challenge of catalyzing the cleavage of a C–C bond in a tradi-
tionally inert alcohol substrate (Scheme 1B, top), it is worth noting that there are only
a few examples of transition-metal-catalyzed aryl additions onto unactivated (i.e.,
aliphatic) ketones, even when employing traditional organoboron nucleophiles
(Scheme 1B, bottom).38–46 Reasons for the limited reports of insertions of ketones
into late transition-metal-carbon bonds include the high bond strength of the
C=O p-bond, increased steric hindrance compared with terminal monosubstituted
a-olefins, and the less favorable interaction between a soft late transition metal cen-
ter and an alkoxide.47 Thus, the development of a shuttle catalysis approach to
ketone arylation is contingent upon addressing two significant challenges in organ-
ometallic chemistry, namely the activation of unbiased C–C bonds and the produc-
tive migratory insertion of ketone substrates into a M‒R species. A shuttle arylation
protocol overcoming these challenges would open new research avenues that take
advantage of reversible b-carbon elimination to parallel the ingenious reactions
developed in the area of transfer hydrogenation and borrowing hydrogen reac-
tions.5–7,11 It would also pave the way for catalytic alternatives to additions with high-
ly reactive stoichiometric Grignard and organolithium reagents. Crucial to unlocking
the desired reactivity is the identification of a suitable catalyst that can lower the acti-
vation barrier of the key transition state for C–C bond cleavage, which is identical to
the one for C–C bond formation by virtue of the microscopic reversibility principle
(Scheme 1B, right).
Herein, we describe a reversible catalytic shuttle arylation reaction between triaryl
alcohols and aliphatic ketones, by cleaving and reforming strong C–C bonds
(Scheme 1C). The reaction does not require directing groups or destabilization of
the alcohol substrates and proceeds in the presence of a range of polar functional
groups. Various aliphatic cyclic and linear ketones, including pharmaceuticals, could
be arylated in good yields using this method.
RESULTS AND DISCUSSION
Catalyst evaluation and reaction development
Inspired by stoichiometric b-carbon elimination studies from rhodium(I) alkoxide
complexes by Hartwig and co-workers,48–50 we envisaged that tuning the steric envi-
ronment around the metal center to stabilize reactive, low coordinated complexes
could unlock a catalytic transfer arylation tolerating a range of unbiased scaffolds.
We began our studies with triphenylmethanol (1a) and 4,40-difluorobenzophenone
(2) as model substrates in the presence of [Rh(cod)Cl]2 and a weak base in toluene
at 110ꢀC. Initially, a panel of ligands was evaluated, and several conditions pro-
moted benzophenone (3a) formation by b-carbon elimination but only trace
amounts of alcohol product 4 were observed. After extensive reaction optimization,
suitable conditions for the transfer of the phenyl group were identified (see Section
S2 for details). NHC ligands effected b-carbon elimination of 1a toward
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A
Proof of concept: reversible aryl elimination from triaryl alcohols
[Rh(cod)Cl]2 (2.5 mol%)
IPr*OMe · HBF4 (5 mol%)
KOtBu (5 mol%)
Ph =
O
O
O
Ph OH
Ph OH
ArF ArF
K3PO4 (1 equiv.)
+
+
ArF
Ph
H
H
+
+
ArF
ArF
PhMe, 125 °C, 24 h
Ph
Ph
Ph
ArF
Ph
Ph
1a
1 equiv.
2
3a
4
5
ArF
=
1 equiv.
After 6 h:
After 24 h:
After 48 h:
19%
75%
83%
11%
7%
2%
3%
58%
86%
F
aromatic ketone
IPr*OMe
R
R
Scrambling of aryl groups electron-deficient group is preferentially cleaved
more stable ketone products predominantly formed
Ph
Ph
N
R
N
R =
MeO
OMe
R
B
Yield of 7a (%)a
Catalytic aryl transfer to aliphatic ketones
Controls
Ligands
No [Rh]
No K3PO4
0
0
[Rh(cod)Cl]2 (2.5 mol%)
IPr*OMe · HBF4 (5 mol%)
KOtBu (5 mol%)
No ligand
BINAP
dppb
Xantphos
IPr
49
31
49
0
69
80
Ph
OH
O
O
Ph OH
Ph
Ph
K3PO4 (1 equiv.)
+
+
PhMe, 125 °C, 24 h
Ph
Ph
IPent
Bases
Cs2CO3
KOtBu
NaH
77
4
57
1a
6a
7a
86%a (81%)b
Conjugation as a driving force
3a
99%a w.r.t. 1a
1.5 equiv.
1 equiv.
aliphatic ketone
Conditions
110 °C
1 mol% [Rh]
0.5 mol% [Rh]
39
70
84c
Scheme 2. Reaction development
(A) Proof of concept of a catalytic reversible shuttle arylation reaction. Reaction conditions: 1a (0.10 mmol), 2 (0.10 mmol), [Rh(cod)Cl]2 (2.5 mol %),
IPr*OMe $ HBF4 (5 mol %), KOtBu (5 mol %) and K3PO4 (1 equiv) in toluene (0.2 M) at 125ꢀC for 24 h. GC-FID yields using n-dodecane as an internal
standard.
(B) Catalytic aryl transfer to aliphatic ketones. Reaction conditions: 1a (0.15 mmol), 6a (0.10 mmol), [Rh(cod)Cl]2 (2.5 mol %), IPr*OMe $ HBF4 (5 mol %),
KOtBu (5 mol %) and K3PO4 (1 equiv) in toluene (0.2 M) at 125ꢀC for 24 h. aGC-FID yields using n-dodecane as an internal standard. bIsolated yield after
purification. c72 h.
benzophenone (3a) and facilitated productive insertion of the aryl group into ketone
2. Among all NHC ligands tested, the electron-rich and sterically demanding ligand
IPr*OMe was identified as the optimal ligand for this transformation (Scheme 2A).51
Interestingly, the major product was not triaryl alcohol 4, but diaryl ketone 5, which
is formed through subsequent b-aryl elimination of the more electron-withdrawing
group from the transiently generated alcohol 4 over the course of the reaction. After
48 h nearly full conversion of both alcohols 1a and 4 toward the ketones 3a and 5,
and (fluoro)benzene was observed.
In an effort to avoid downstream reactions of the desired alcohol product, we next
sought ways to take advantage of this unique reactivity to develop a synthetically
attractive reaction. We reasoned that using an aliphatic ketone as acceptor would
be beneficial because: (1) the tertiary alcohol product would likely not have the abil-
ity to scramble through cleavage of a strong C(sp3)–C(sp3) bond, preventing unde-
sired crossover reactions; (2) the overall transfer reaction would likely be exergonic
Chem 7, 1108–1119, April 8, 2021 1111

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due to the formation of a conjugated ketone by-product as driving force (DFT pre-
dicts DG = ꢁ4.0 kcal molꢁ1), while no deconjugation of the acceptor substrate
(aliphatic ketone) would take place (see Section S7). Indeed, the reaction of 1a
and 4,4-dimethylcyclohexanone (6a) worked efficiently and reached full conversion
with only marginal excess (1.5 equiv) of the donor (Scheme 2B). The desired alcohol
product 7a was obtained in excellent yield, while 1a was converted into ketone 3a
and benzene as a side product (by protodemetalation). Control experiments
confirmed the essential role of the catalyst and a weak base. Sterically encumbered
NHC ligands resulted in the highest yield, but other ligands also effected product
formation. Notably, the reaction could even be conducted at 0.5 mol % catalyst
loading, albeit with prolonged reaction time.
Substrate scope
After finding the optimal conditions, we investigated the generality and utility of this
transformation. A range of cyclic (6a–b) and linear (6d–e) aliphatic ketones were effi-
ciently arylated to afford the corresponding tertiary alcohols in good yields (Scheme
3A). Acetophenone could also be arylated, albeit the formation of product 7c was
reversible, leading to a diminished yield. Sterically hindered ketones were unreactive
under the reaction conditions, which might indicate that bulky ketones are unable to
approach the sterically encumbered catalyst (Scheme S1). Several functional groups
were found to be compatible with the reaction conditions, such as ketal-protected
ketones (7f), protected amines (7g), ethers (7h), and sulfones (7i). Notably, substrates
containing sensitive functional groups toward Grignard and organolithium reagents
underwent the arylation at the ketone selectively, leaving carboxylic esters (7k–l), am-
ides (7m), and Weinreb amides (7n) untouched. Cross-coupling handles such as aryl
silanes (7j) and chlorides (7o) remained unchanged, offering the potential for orthog-
onal synthetic manipulation. The arylation also proved to be effective in the presence
of a heterocyclic residue (7p). Electrophilic moieties, such as alkyl tosylates (7q) and
bromides (7r), and even epoxides (7s) were tolerated, revealing the mildness of this
method. Protic functionalities such as alcohols did not interfere with the reaction,
furnishing diol 7t as a mixture of diastereomers. Drug molecules, such as nabume-
tone and pentoxifylline, underwent arylation in good yields (7u–v), demonstrating
the potential for late-stage derivatization of bioactive compounds.
To further showcase the scalability and robustness of this reaction, the transfer ary-
lation of 1a and 6d was conducted on 10 mmol scale with a reduced catalyst loading
of 1 mol % (Scheme 3B). The alcohol product (7d’) was obtained in 70% yield after
purification. The second product, benzophenone (3a’), was recovered in 77% with
respect to 1a, or 116% based on the limiting reagent 6d.
Subsequently, we turned our focus to the alcohol scope. We first investigated
several symmetrical triaryl alcohols 1 (Scheme 4A). A range of alkyl-substituted alco-
hols (8a–c) and a 2-naphthyl group (8d) were suitable donor molecules, affording the
desired alcohols in good to excellent yield. Moreover, several common functional
groups were tolerated, such as fluoro (8e), chloro (8f), methoxy (8g), trifluoromethyl
(8h, 8j), and trifluoromethoxy (8i) groups. The reaction was efficient with both elec-
tron-rich and -deficient donors, albeit the yield of 8g and 8j was limited due to fast
consumption of the alcohol starting material via protodemetalation. Notably, het-
erocyclic scaffolds could be readily used and allowed the transfer of 1,3-benzodiox-
olane (8k), benzofurane (8l–m), and morpholine (8n) moieties.
Beyond triaryl alcohols, we investigated the propensity of other alcohols to undergo
b-carbon elimination (Scheme 4B). 1,1-Diphenylethanol (1p) afforded product 9a in
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Scheme 3. Scope of ketone acceptors
aRatio determined by 1H NMR of the crude reaction mixture.
moderate yield because the formation of the by-product acetophenone is reversible (7c,
vide supra). Excitingly, a 2ꢀ alcohol (1q) could be engaged to afford the product 9b in a
promising yield, showing potential for productive b-carbon elimination in the presence
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A
[Rh(cod)Cl]2 (2.5 mol%)
IPr*OMe HBF4 (5 mol%)
KOtBu (5 mol%)
Ar
O
O
+
+
OH
Ar
HO
K3PO4 (1 equiv.)
Ph
Ar
Ar
PhMe
125 °C, 24 h
Ar
Ph
1
6d
8
3
1.5 equiv.
1 equiv.
Symmetrical alcohols
tBu
F
HO
HO
HO
HO
HO
Ph
Ph
Ph
Ph
Ph
8d, 87%
OCF3
8e, 68%
F3C
8a, 68%
8b, 51%
8c, 70%
Cl
OMe
CF3
CF3
HO
HO
HO
HO
HO
Ph
Ph
Ph
Ph
Ph
8f, 76%
8g, 47%
8i, 75%
8j, 39%
8h, 80%
O
O
O
N
O
O
HO
HO
HO
HO
Ph
Ph
Ph
Ph
8k, 46%
8l, 68%
8m, 55%
8n, 69%
B
[Rh(cod)Cl]2 (2.5 mol%)
IPr*OMe HBF4 (5 mol%)
KOtBu (5 mol%)
O
O
+
+
OH
R2
HO
R3
K3PO4 (1 equiv.)
R3
R4
R1
R2
R1
1p-q
R4
PhMe
125 °C, 48 h
6a or 6d
1 equiv.
9
3
1.5 equiv.
Non-symmetrical alcohols
Ph
H
Ph
OH
Ph
OH
HO
OH
Ph
9a, 54%
1p, diaryl alcohol
9b, 26%
1q, 2° alcohol
Scheme 4. Scope of alcohol donors
of a competing b-hydride. We surmise that rapid and reversible b-hydride elimination
occurs under the reaction conditions, yet the final formation of the desired tertiary
alcohol kinetically traps the occasionally formed b-carbon elimination intermediate,
hence slowly driving the mixture toward the desired product. This result thus suggests
the possibility to merge complex sequences of reversible b-hydride and b-carbon elim-
inations, opening new avenues for the manipulation of alcohols in catalysis.
Preliminary mechanistic studies
After demonstrating the synthetic versatility of this protocol, we performed experi-
ments to investigate the reaction’s reversibility. To confirm that b-carbon elimination
is reversible for triaryl alcohols 1, diaryl ketone 3b was added to the reaction mixture
of 1a and 6a (Scheme 5A). Incorporation of both the phenyl group (red) and the p-
tolyl group (blue) into 6a was observed in a 4.9:1 ratio, together with a mixture of
all three possible diaryl ketones, confirming that addition into diaryl ketone 3b is
reversible and has a similar rate to the addition into aliphatic ketone 6a.
To evaluate the reversibility of the reaction in the case of (dialkyl)aryl alcohols 7,
alcohol trans-7b, and benzophenone (3a) were subjected to the reaction conditions
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Scheme 5. Mechanistic experiments
(A) Crossover experiment.
(B) Stereochemistry as a mechanistic probe for reversibility.
(C) Hammett study.
(D) Precatalyst synthesis, catalytic competence, and crystal structure.
(Scheme 5B). Notably, isomerization to the more stable cis-isomer and small
amounts of ketone 6b were observed, highlighting that b-aryl elimination from (dia-
lkyl)aryl alcohols also takes place, albeit the reaction rate is much lower than for tri-
aryl alcohols.
To gain insight into the electronic preference of the reaction, intermolecular compe-
tition experiments with two symmetrical triaryl alcohols were carried out (Table S12).
Interestingly, both electron-rich and -deficient substituted aryl groups were prefer-
entially cleaved compared with phenyl, with no correlation between the electronic
character and the observed selectivity. Notably, a similar trend was observed in
Pd-catalyzed b-aryl elimination.52 The interpretation of these results is, however,
complicated by the partial reversibility of the addition of one aryl group to another
diaryl ketone by-product leading to crossover products (see Scheme 5A). To reduce
the impact of these effects, the initial rates using different triaryl alcohols and an
excess of ketone acceptor were independently measured and plotted against the
Hammett parameter s+ (Scheme 5C).53 In this case, a linear-free-energy relationship
with a negative slope was observed (r = ꢁ0.62, R2 = 0.91). Based on the obtained r
value and the better correlation with the s+ parameter, we can conclude that there is
a partial positive charge buildup on the benzylic carbon in the turnover-limiting step
of the reaction.
We next independently synthesized the complex [Rh(IPr*OMe)(cod)Cl] (10) that is pre-
sumedly formed in situ (Scheme 5D). The complex was catalytically competent,
effectively giving the same yield of the product. The crystal structure obtained by
X-ray diffraction of the air-stable complex illustrates the steric encumbrance of the
NHC ligand around the substrate-binding site. The steric influence of the ligand
was parameterized by its buried volume (Vbur).54 While the buried volume of IPr*OMe
˚
is slightly larger than that of IPr at 3.5 A radius (Vbur = 37.2% versus 33.6%), its reach
˚
extends further in the periphery (Vbur = 46.4% versus 38.6% at 5.5 A).
Based on these preliminary observations, we propose the following reversible cata-
lytic cycle (Scheme 6). Ligand exchange of complex I (10) with the alcohol substrate
followed by dissociation of a cod ligand creates the presumed catalytically active
species II. As in the case of b-hydride elimination, an empty coordination site is a
requisite for b-carbon elimination to occur. The coordinatively unsaturated Rh center
in II likely interacts with one of the aryl rings in a h2-fashion, as has been shown in X-
ray structures of related complexes,48 thereby facilitating the C–C bond cleavage.
Aryl complex III then undergoes reversible ketone exchange to form complex IV
that in turn is set up for migratory insertion of the ketone to form alkoxide complex
V. Every step in the catalytic cycle is reversible according to our findings. Finally,
alcohol exchange closes the cycle.
Conclusions
In summary, we have developed a catalytic shuttle arylation reaction that cleaves un-
activated C(sp2)–C(sp3) bonds in unstrained alcohols and arylates unactivated
aliphatic ketones. This is the first example of a reversible transfer hydrocarbylation
reaction that parallels the ubiquitous transfer hydrogenation reaction of secondary
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Scheme 6. Proposed catalytic cycle
alcohols and carbonyl acceptors. Using this method, triaryl alcohols can be used as
latent nucleophilic aryl sources for traditionally challenging catalytic additions to ke-
tones. Preliminary mechanistic studies point toward reversible C–C bond activation
as a key factor in enabling this process. In a broader context, this novel reactivity of-
fers numerous opportunities for the creative use of tertiary alcohols in synthesis
which parallel major achievements made in transfer hydrogenation and borrowing
hydrogen reactions.
EXPERIMENTAL PROCEDURES
Resource availability
Lead contact
Further information and requests for resources should be directed to and will be ful-
filled by the Lead Contact, Bill Morandi (bill.morandi@org.chem.ethz.ch).
Materials availability
All unique/stable reagents generated in this study are available from the lead con-
tact without restriction.
Data and code availability
Crystallographic data for 7a, cis-7b, and 10 have been deposited in the Cambridge
Crystallographic Data Center (CCDC) under accession numbers CCDC: 2035749,
2035750, and 2035751. These data can be obtained free of charge from the
Chem 7, 1108–1119, April 8, 2021 1117

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CCDC at https://www.ccdc.cam.ac.uk/structures/. All other data are available from
the lead contact upon reasonable request.
SUPPLEMENTAL INFORMATION
Supplemental information can be found online at https://doi.org/10.1016/j.chempr.
2021.02.029.
ACKNOWLEDGMENTS
We thank the European Research Council (ERC grant 757608 ShuttleCat), the Swiss
National Science Foundation (SNF 184658), and the ETH Zurich for financial support.
¨
M.D.R.L. is grateful for funding from the German Academic Scholarship Foundation.
We thank the NMR service, the Molecular and Biomolecular Analysis Service (Mo-
BiAS), and X-ray departments of ETH Zurich for technical assistance. We thank the
¨
Morandi group members for the critical proofreading of the manuscript.
AUTHOR CONTRIBUTIONS
M.D.R.L. and B.M. conceived the project. M.D.R.L. discovered and developed the
reaction; M.D.R.L. and V.C.M.G. conducted the synthetic studies. All authors
contributed to the writing and editing of the manuscript.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: November 3, 2020
Revised: February 3, 2021
Accepted: February 24, 2021
Published: March 25, 2021
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