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Carbonyl-Olefin Metathesis Catalyzed by Molecular Iodine Uyen Phuoc Nhat Tran, Giulia Oss, Martin Breugst, Eric Detmar, Domenic Paul Pace, Kevin Liyanto, and Thanh Vinh Nguyen ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03769 • Publication Date (Web): 14 Dec 2018 Downloaded from http://pubs.acs.org on December 15, 2018
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is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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ACS Catalysis
Carbonyl-Olefin Metathesis Catalyzed by Molecular Iodine Uyen P. N. Tran,a Giulia Oss,a Martin Breugst,b Eric Detmar,b Domenic P. Pace,a Kevin Liyantoa and Thanh V. Nguyena,* a b
School of Chemistry, University of New South Wales, Sydney, Australia Department für Chemie, Universität zu Köln, Köln, Germany
Supporting Information Placeholder ABSTRACT: The carbonyl-olefin metathesis reaction
could facilitate rapid functional group interconversion and allow construction of complicated organic structures. Herein we demonstrate that elemental iodine, a very simple catalyst, can efficiently promote this chemical transformation under mild reaction conditions. Our mechanistic studies revealed intriguing aspects of activation mode via molecular iodine and iodonium ion that could change the previously established perception of catalyst and substrate design for the carbonyl-olefin metathesis reaction.
Catalytic Carbonyl-Olefin Metathesis (COM) Reaction R2 R1
27 examples 21-96% practical on gram scale broad substrate scope (all three COM reaction types)
Previously: Lambert’s hydrazine catalyst NH NH
The carbonyl-olefin metathesis reaction (COM),1 an analogue of the olefin-olefin metathesis reaction,2 is considered to be very useful for direct carbon-carbon bond forming transformations and functional group interconversions. There had been a number of developments on experimental protocols3 and catalysts4 for the COM reaction. Over the last five years, it has become increasingly attractive after interesting studies from the Lambert group using hydrazine5 and the Franzen group using tritylium salts6 as organocatalysts for this reaction (Scheme 1). More recently, the Schindler group7 and the Li group8 reported elegant studies in which they utilized salts of iron(III) and gallium(III) to promote COM reactions. Earlier this year, the Tiefenbacher group also published an interesting report on the cooperative effect of hexameric resorcinarene assembly and Brønsted acid to catalyze COM reactions.9 A recent study from our laboratory showed that tropylium ion10 could also be used as an organocatalytic promoter for the COM reaction (Scheme 1).11 The COM reaction is, however, still much less investigated than the olefin-olefin metathesis,12 most likely due to a lack of practicability and general knowledge about rational catalyst and substrate design for the reaction. Herein we demonstrate that elemental iodine, a very simple catalyst, can efficiently promote the COM reaction on a broad range of substrates under
.
(ref 5)
(ref 7a-d and 8)
intramolecular COM only GaCl3
Franzen’s tritylium catalyst Ar
2HCl
Schindler’s and Li’s catalyst FeCl3
R2
O
rt, 24 h via iodonium catalysis
ring-opening COM of cyclopropene only
INTRODUCTION
R1
This work: [cat.] = I2
O
Ar
Ar
X
(ref 6)
intermolecular COM only
Tiefenbacher’s catalyst HCl inside hexameric (ref 9) resorcinarene host intramolecular COM only
(ref 7e)
ring-opening COM only
Our tropylium catalyst
BF4 (ref 11)
all three types: intra/inter-molecular and ring-opening
Scheme 1. Catalytic carbonyl-olefin metathesis reaction mild conditions with excellent outcomes. The inspiration for our use of iodine as a promoter for the COM reaction came from previous reports of iodine being able to activate carbonyl substrates for a range of chemical reactions via halogen bonding interaction.13 Elemental iodine can also serve as a pre-catalyst for iodonium-activation of alkenes14 or alkynes15 in isomerization and cyclization reactions. We predicted that iodine could either activate the carbonyl moiety or the alkene moiety, or cooperatively activate both functional groups for the carbonyl-olefin metathesis reaction. Thus, we set out to test our hypothesis by using I2 catalyst to promote the intramolecular COM reaction of substrate 1a1 (Scheme 2).
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R1
O
R3
R4
2a’
Ph
O
CO2Me
CO2Et
200 mg, 93% (2a : 2a’ = 11 : 1) 1.60 g, 89% (2a : 2a’ = 38 : 1)
1a1
Products
Me
CO2Et
2a
2l, 23%
1l
O
Me CO2Et
CO2Et
2a
1a2
2m 1m
Ph
2m’
94% (2m : 2m’ = 2.5 : 1)
27% (2a : 2a’ = 11 : 1)
O
AND
H 2C
Me
H CO2Et
CO2Et
2a
1a3
Me
O
CO2Et
2a’
Me
CO2Et
Me
Me
AND CO2iPr
CO2
2c
iPr
Me
MeO
AND
MeO
Me
H
2p, 47% Me
O
MeO CO2Et
2d
1d
Me Me
1p
CO2Et
CO2Et
N
O
AND O
Ph 1e
N
O
2e
Ph
2g’
Me Allyl
Allyl
CO2Et
O
Br
Me Allyl
Me
Me N
Me Ts
Me CO2Et 1k
CO Et Me 2 2k, 54%
2t (*), 78%
N
N Ts
Me Ts Me
1v
2u (*), 86%
Me N
Me Ts
Ph
Scheme 2. Iodine-catalyzed intramolecular carbonyl-olefin metathesis reactions16 ACS Paragon Plus Environment
Br
1u
O
Me
O
N Ts
Me
2j, 58%
1j
Me
Me 2s, 54%
Me Allyl
N Ts
1t
O
Me
Me
Ts
2i, 46%
1i
O
2s 104 mg, 92% 1.51 g, 91%
H
1s2
2h, 59%
CO2Et
N Me
Me CO2Bn
Me
Ph
O
Me
O
Me
1s1
Ph
Me
N Ts
Me Ts
Me
Me
CO2Bn 1h
N
Me
42% (2g : 2g’ = 1 : 3)
O
Me
O
AND
2g
1g
2r, 96%
2e’
Ph
Ph
Me
1r
60% (2e : 2e’ = 1 : 3)
Me
N Ts
Me Ts
Me
Ph
Me
O
2q (*), 82% Me
Me Me
N Ts
Me Ts
1q
2d’ 83% (2d : 2d’ = 4 : 1)
O
2o’, 32%
2c’
58% (2c : 2c’ = 2.1 : 1)
O
Me
1o
O
Me
1c
Me
2b’ 76% (2b : 2b’ = 2 : 1)
CO2iPr
Me
O
CO2Et
2b
O
2n’ 54% (2n : 2n’ = 1 : 1)
AND
Me
1b
Me
2n
1n
Me
CO2Et
O
AND
Me
48% (2a : 2a’ = 11 : 1)
O
Me Me
AND
Me
Me
2a’
H 2C
Me
Me
AND
CO2Et
3
Me
O
CO2Et
CO2Et
O
Substrate
AND
Me Me
R2
2’ (isomerized product)
2 (COM product)
Products
R1
( )n R4
R4
(*) = using 25 mol% cat. I2
Substrate
R3
( )n
neat, rt, 24 h
1 (see pages S5-S17 in the SI)
O
R3
10 mol% I2
( )n R2
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N Ts Ph 2v, 76%
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RESULTS AND DISCUSSIONS Gratifyingly, our preliminary investigation immediately showed very promising outcomes: within 24 hours at 50 ºC using 5 mol% of I2 as catalyst, substrate 1a1 was converted to the cyclized COM product 2a and its isomerized product 2a’ in 62% total yield (~ 90% conversion).16 Subsequent optimization studies (see page S3 in the SI) revealed that the reaction could be carried out smoothly and cleanly at ambient temperature and atmosphere in solvent-free conditions using 10 mol% I2 catalyst, giving the products 2a and 2a’ in 93% total yield after purification.16 The optimal conditions were effective for a wide range of substrates (Scheme 2). Most of products 2 were obtained in moderate to excellent yields from generally clean intramolecular COM reactions when substrates 1 bear the isopropylidene moiety (i.e. when acetone is formed as a by-product, Scheme 2, see page S5-S17 in the SI for the specific structures of COM precursors 1).16 Substrates with active olefin moieties bearing different substituents (such as Ph or H) also cyclized via the COM reactions, albeit with lower yields (Scheme 2, comparison of entries 1a1 to 1a2-1a3 and entries 1s1 to 1s2). This phenomenon has been previously observed with transition metal Lewis acid catalysts7a-d,8 and our own tropylium catalytic system. This new protocol can be practically carried out on gram scale with very high efficiency, as demonstrated for substrates 1a1 and 1s1 to form 1.60 g of 2a and 1.51 g of 2s respectively (Scheme 2).16 The most notable feature of this protocol is that it only required short reaction time at ambient temperature to achieve similar results to the COM reactions promoted by other catalytic systems7a-e,8-9,11 at harsher conditions. As expected with the benign nature of the iodine catalyst and the mild reaction conditions, this COM protocol tolerates several types of functional groups. Most of the non-nitrogen containing substrates (1a-1p) went through the iodine-catalyzed COM reactions to give a mixture of two regioisomeric products. When the functional group at the α-position of the newly formed C-C double bond is a alkoxycarbonyl group, the expected COM products (2a-2d and 2h) were produced as major components. When this functional group is an acyl group, phenyl ring or methyl group, the isomerized olefins were formed as the major products (2e’, 2g’ and 2o’). The formation of these isomerized products can be attributed to isomerization of the C-C double bond, generated after the COM reactions, presumably due to traces amounts of Brønsted acids present in the reaction mixture (Table 1, vide infra). The Tiefenbacher group also reported similar observations in their Brønsted-acid catalyzed COM reactions.9 These regioisomeric ratios changed with modifications of reaction conditions (Scheme 2) and we observed the isomerization (2a to 2a’, see page S31 in the SI for more details) when subjecting the pure product 2a to the same I2-catalyzed COM reaction conditions.
Substrates bearing Brønsted-basic nitrogen-centers8 did not undergo this type of isomerization (Scheme 2, 2q-2v). They worked smoothly to give cyclized COM products exclusively in high to excellent yields (2q-2v), although substrates without substitution on the carbon between the carbonyl and the nitrogen centres required higher catalyst loading for efficient reactions (Scheme 2, see products 2q, 2t and 2u, 25 mol% I2 was used).16 Apart from the driving force due to the formation of acetone as a by-product, stabilizing effect from the conjugation of the aromatic ring to the carbonyl group is also essential for this iodine-catalyzed COM reaction, as non-aromatic substrate 1l was only converted to bicyclic product 2l in poor yield (see page S12 in the SI for more unproductive non-aromatic substrates).16 When the distance between the carbonyl and the olefin moieties was varied with different carbon chain linkers (1’, Scheme 3a), the reaction outcomes changed vastly. γ,δ-Olefin ketone (n = 1) gave the 3,4-dihydro-2H-pyran 4, presumably via a 6-endo-trig cyclization process similar to what were reported by Schindler and coworkers,17 while δ,ε-olefin ketone (n = 2) gave the normal COM products (2a and 2a’). ε,ζ-Olefin ketone (n = 3), on the other hand, did not convert to any cyclized products (see page S19 in the SI for more unproductive ε,ζ-olefin ketone substrates).16 presumably via 6-endo-trig cyclization of 4’ [see ref 17]
(a)
I
O
with n = 1
O
CO2Et
CO2Et
4’
4, 89%
O
with n = 2 COM reaction
10 mol% I2
n
AND CO2Et
neat, rt, 24 h
CO2Et
H
CO2Et
2a 93% (2a : 2a’ = 11 : 1) 2a’
1’ no COM reaction no cyclization reaction ~ 80% recovered SM 1’ (see the SI page S19 for more details)
with n = 3
(b)
O
5
neat, rt, 24-72 h
6
Me
7a, 50%
O
7
R
Me
R
Ar
10 mol% I2
H
Ar
nBu
CO2Me 7b, 34%
3a
7c, 39%
MeO
Ph 7d, 31%
with 6 as ring-opening COM reaction
7e, 50%
O
7f, 21%
O
Scheme 3. (a) COM reactions with different chain lengths; (b) Intermolecular COM reactions
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This newly developed I2-catalyzed protocol was subsequently tested on the intermolecular COM reactions between aromatic aldehydes 5 and isopropylidenyl olefins 6 (Scheme 3b). This type of reaction were reported previously by the Franzen group and our group using tritylium6a and tropylium11 salts as catalysts, respectively. In both cases, only low to moderate efficiencies were obtained, most probably because the intermolecular COM reaction is not as entropically favoured as the intramolecular reaction. Our reactions afforded 31-50% of the intermolecular COM adducts (7a-7d, Scheme 3b), which were comparable results to previous studies.6a,11 The intermolecular ring-opening COM reactions with 1methylcyclopentene, identified as the best substrate for this type of reaction in our previous study,11 also gave low product yields (7e and 7f). Nevertheless, these reaction outcomes are comparable with similar reactions promoted by our tropylium catalyst11 or Schindler’s gallium(III) catalyst,7e which potentially paves the way for future development in this field based on the simplicity of the iodine catalytic system. At this stage, it became very interesting to us to understand how such a simple catalytic system like iodine can promote this previously considered challenging COM reaction. In principle, there are four potential pathways18 how this iodine-promoted reaction can proceed through:13a,13b,13e (i) Brønsted-acid catalyzed9 pathway with HI formed in situ from I2;13e (ii) Radical-initiated pathway from homolytic cleavage of I2 (by light or air);19 (iii) Halogen-bonding assisted pathway with molecular iodine I-I;18a (iv) Lewis-acid catalyzed pathway with iodonium ion (I+) formed in situ by the heterolytic cleavage of I2.18a A halogen-bond activation was recently proposed for the iodine-catalyzed Michael addition to α,β-unsaturated carbonyls as both Brønsted-acid and iodonium-ion catalysis were unlikely under the reaction conditions.18 Thus, we carried out a range of mechanistic studies to get further insights into the mode of activation by iodine (Table 1, see page S24 in the SI for more details).16 Replacement of elemental iodine with HI or KI resulted in non-productive reactions (entries 2-3, Table 1), suggesting that iodide anion and Brønsted acid have no significant role in this reaction. Carrying the reaction with I2 catalyst in the dark (entry 4) or with a radical scavenger (BHT, see entry 8) still gave full conversions of 1a1 to the products while BHT itself has no effect on the reaction (entry 9), hinting that the radical pathway can also be ruled out. A series of reactions with I2 catalyst, where we excluded the presence of moisture and air (entry 5) or just air (entries 6-7), met with significant reductions in the conversions of 1a1. These demonstrated that air did participate in promoting the reaction, most likely through the oxidation of molecular iodine or iodide ion to higher oxidation states. However, when we tried to recreate this oxidative environment in a controlled manner using m-CPBA (entry 10) or hydrogen peroxide
(entry 11), they only resulted in low conversion of 1a1 to the product. Two other iodonium sources, namely NIS and ICl, were also tested as catalysts for this COM reactions (entries 12 and 15). These reactions gave very positive outcomes, supporting the iodonium-catalyzed pathway with I2 catalyst. That it was not the succinimide component catalyzing the reaction is confirmed by entry 14 where NBS could not convert any of 1a1 to the products. Interestingly, when we added DMSO (20 mol%, 2 equiv to NIS catalyst, entry 13, Table 1), a very good iodoniumbinding solvent,20 to the reaction, it completely turned off the catalytic activity of NIS. Similar results were observed with the addition of DMSO (20 mol%) to the original I2 (10 mol%) catalyzed reaction conditions (entry 16, compared to entry 1), which was not too surprising as DMSO can also coordinate to I2.21 The addition of potassium iodide (10 mol%), which could suppress the formation of iodonium ion (I+) and combine with molecular iodine to form triiodide (I3-), also negatively affected the reaction outcomes (entry 17). These experiments once again confirmed the possibility of the iodonium ion being the actual active catalyst in this COM reaction. Due to the presence of moisture, it is possible that some hypoiodous acid (HOI) could form from the disproportionation of the molecular iodine and play some roles in this reaction.22 However, under oxidative conditions such as in entry 11, which should favor the formation of HOI,23 the reaction outcomes were rather poor. We further examined this possibility by carrying out the COM reaction with 10 mol% I2 in the presence of 10 mol% KOH (entry 18, Table 1), which could form potassium hypoiodite (KOI) in situ. This reaction gave a messy mixture with only trace amounts of the wanted COM products, suggesting that a hypoiodous/hypoiodite pathway is unlikely. On the other hand, although we cannot completely rule out the possibility of activation by direct halogen-bonding interaction from molecular iodine based on the experimental investigations,18a entries 19-22 in Table 1 were indicative that halogenbonding activation is unlikely to be the driving force for this type of reaction. Indeed, the use of catalytic or stoichiometric amounts of pentafluorophenyl iodide (entry 19), a frequently used halogen-bond donor,24 did not result in any reaction. Similarly, using triphenylphosphine diiodine (entry 20) and Huber’s monodentate or bidentate iodoazolium salts25 (entries 21-22), all very good halogen-bonding donors but not iodonium sources, did not lead to formation of the COM products. We furthermore carried out kinetic studies to determine the reaction order with respect to the iodine catalyst. The kinetic studies were performed by 1H NMR spectroscopy at different catalyst loadings (8 to 14 mol%), as the reaction was too slow or too fast outside this range.16 For higher iodine loadings (>10 mol%) we
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observed a good linear correlation with a slope of 1 in double-logarithmic plots. The data point for low catalyst loading (8 mol%) deviates slightly from the above and if it was taken into account, a slope close to 2 was obtained (see page S26 in the SI). These outcomes were reproduc-
ible from a triplicate. Based on the kinetic data, it is rather unlikely that I3- or any other higher iodine aggregate is involved in the rate-limiting transition state. Arguably, the reaction order in the catalyst is around 1 and
Table 1. Mechanistic studies of the I2-catalyzed COM reaction with substrate 1a116
O
cat. CO2Et
neat, rt, 24 h
1a1
Entry
a
+ CO2Et 2a (major)
+ CO2Et 2a’ (minor)
O
3a b
Catalyst (10 mol%)
Additive
Conditions
1
I2
-
air, lab light
100%
2
KI
-
air, lab light
no reaction (8%)d
3
HI
-
air, lab light
no reaction
4
I2
-
air, in the dark
100%
5
I2
-
N2, lab light
30% (100%)d
6
I2
water (10 mol%)
N2, lab light
10%
7
I2
water (10 mol%)
N2, in the dark
16%
8
I2
BHT (100 mol%)
air, lab light
100%
9
-
BHT (100 mol%)
air, lab light
no reaction
10
I2
m-CPBA (10 mol%)
N2, lab light
7%
11
Conversion
I2
H2O2 (10 mol%)
N2, lab light
10%
c
NIS
-
air, lab light
48% (100%)d
13 c
NIS
DMSO (20 mol%)
air, lab light
no reaction
14
NBS
-
air, lab light
no reaction
15
ICl
-
air, lab light
62% (100%)d
16
I2
DMSO (20 mol%)
air, lab light
3%
17
I2
KI (10 mol%)
air, lab light
12%
18
I2
KOH (10 mmol%)
air, lab light
messy reaction
-
air, lab light
no reaction
-
air, lab light
no reaction
-
air, lab light
no reaction
-
air, lab light
no reaction
12
F
19
F
I
F
F F
20
Ph3P-I2 nOct
N
21
I N Me
OTf 2 BArF4
22
N N nOct
N I
I
N nOct
a
Reaction conditions: substrate 1a (0.5 mmol) and catalyst/additive were stirred for 24 h at rt; bAir means the reaction was carried out without exclusion of air. Normal lab light means fumehood lighting (4 x 13W fluorescent lamps); cNIS was recrystallized; dConversion in the parentheses were recorded after 72 h.
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the iodine dissociation probably occurs only ‘partially’, e.g., through the formation of very tight ion pairs. Based on these mechanistic studies, we hypothesized a mechanistic pathway in which the I+ ion acted as a Lewis acid to activate the carbonyl moiety and trigger the oxetane formation event (1a1 to 10, Scheme 4). Presumably, the oxetane intermediate 10 subsequently rearranges to the cyclized product 2a similar to how it works with the other acidic catalysts.6a,7a-d,8-9,11 To further probe the reaction mechanism, we additionally employed DFT calculation at the M06-2X/aug-ccpVTZ/IEFPCM//M06-2X/6-311+G(d,p)/IEFPCM with the aug-cc-pVTZ-PP for I] level to validate this proposed mechanism (Scheme 4). In line with the experimental observation that the reverse reaction of a mixture of 2a and 3a (in excess) did not proceed to form 1a1 under the same catalytic conditions (see page S31 in the SI),16, the calculations predict a substantial thermodynamic driving force for the COM reaction (Scheme 4, ΔG = –11.9 kcal mol–1). Furthermore, the computational investigations indicate that a putative halogen-bond activation by I2 requires an activation free energy of 51 kcal mol–1. Compared to the uncatalyzed reaction, this pathway is still favourable (ΔΔG‡ = 6.7 kcal mol–1) but very unlikely due to the high activation free energy (see the computational SI for more details). Our calculations on an iodonium-ion pathway are summarized in Scheme 4. While our calculations predict a very endergonic splitting of molecular iodine due to
Page 6 of 9
unfavorable charge separation (see the computational SI for more details), experimental data suggest equilibrium constants between 1.4 × 10–5 (ΔG = +6.5 kcal mol–1) and 1.8 × 10–10 (ΔG = +13.3 kcal mol–1) for this process.26 As different solvation models (IEFPCM,27a refined SMD,27b,c and CPCM27d–g) resulted in very similar energies, this deviation is most likely caused by charge separation and only to a small extent by an insufficient solvation model. Consequently, we decided to use the latter experimental value for our calculations. As a consequence, the calculated free energy differences will constitute an upper limit for these processes and the real number might even be smaller. Based on our calculations, the rate-limiting transition state is the nucleophilic attack of the alkene onto the activated carbonyl (TS1, Scheme 4), i.e., the first step of the [2+2]-cycloaddition. All subsequent transition states are significantly lower in energy. This energy profile is therefore slightly different to that obtained by Schindler and coworkers for the FeCl3-catalyzed reaction where all transition states were comparable in energy.7a Our calculations furthermore indicate that the addition of iodine to the double bond is thermodynamically unfavorable (ΔG = +6.6 kcal mol–1) and is consequently not observed under the reaction conditions. Therefore, the computational data support the picture of an iodonium-ion pathway as the origin of the catalytic activity of molecular iodine in COM.
I
O
I2
I
I
O
TS1
8
9
TS3
Ph
MeO2C
CO2Me
CO2Me
I O
TS2
Ph
Ph
Ph
I O
I O
13
TS4
O I
I2
3a +
+
Ph Ph
MeO2C
Ph
MeO2C 12
11
10
O
MeO2C
MeO2C
14
14
ΔG / kcal mol–1 TSuncat2 +57.6
+60 TSuncat1 +50.2
+50 +40
TS1 +29.8
+30 +20
10 +22.1 9 +13.3
+10 0 –10
TS2 +22.9
8 + I2 0.0
11 +10.1
TS4 +17.8
TS3 +16.1 12 +13.3
+2.7 13 + 14 –2.4 14 + 3a + I2 –11.9
–20
Scheme 4. Gibbs free-energy profile for the uncatalyzed and the iodonium-ion-catalyzed carbonyl-olefin metathesis.
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ACS Catalysis
CONCLUSION We have developed a new practical protocol for the intramolecular carbonyl-olefin metathesis reactions using elemental iodine as catalyst. This method is easy to set up with very mild reaction conditions and involves an inexpensive and benign catalyst while offering comparable outcomes to previously reported procedures. Preliminary mechanistic studies revealed the important role of the in situ generated iodonium ion, which might promote the COM reaction via the activation of the carbonyl moiety. Further applications of this new method in organic synthesis are ongoing and will be reported shortly. AUTHOR INFORMATION Corresponding Author
T.V. Nguyen, email:
[email protected] Funding Sources The authors declare no competing financial interests.
ASSOCIATED CONTENT Supporting Information Experimental procedures, characterization data, NMR spectra and details of the computational investigations are available free of charge on the ACS Publications website.
Keywords Carbonyl-olefin metathesis; olefination; iodine; iodonium; catalysis; metal-free
A CKNOWLEDGMENT This work is financially supported by Australian Research Council (grant DE150100517 to TVN). Additional support from the Fonds der chemischen Industrie (Liebig scholarship to MB) and the DFG (BR 5154/2-1) is gratefully acknowledged. We are grateful to the Regional Computing Center of the University of Cologne for providing computing time of the DFG-funded High Performance Computing (HPC) System CHEOPS as well as for their support.
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Carbonyl-Olefin Metathesis (COM) Reaction R2 R1
O
R1
cat. I2 10 mol%
R2
O neat, rt, 24 h 27 examples 21-96% practical on gram-scale
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