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Decarboxylative Elimination of N-Acyl Amino Acids via Photoredox/Cobalt Dual Catalysis Kaitie C. Cartwright, and Jon A Tunge ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03282 • Publication Date (Web): 09 Nov 2018 Downloaded from http://pubs.acs.org on November 9, 2018
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ACS Catalysis
Decarboxylative Elimination of N-Acyl Amino Acids via Photoredox/Cobalt Dual Catalysis Kaitie C. Cartwright, Jon A. Tunge* Department of Chemistry, The University of Kansas, 2010 Malott Hall, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, United States. Supporting Information Placeholder ABSTRACT: A dual catalytic strategy for the synthesis of enamides and enecarbamates directly from easily accessible and inexpensive amino acids has been realized. This mild and efficient protocol makes use of an organic photoredox catalyst and a cobaloxime catalyst to achieve decarboxylative elimination using hydrogen evolution to drive the oxidation. Thus, the reaction occurs without a stoichiometric oxidant or the forcing conditions previously employed in attempts to achieve similar eliminations.
Enamides and enecarbamates possess synthetic utility as stable nucleophilic building blocks in addition to the motif itself being present in biologically active compounds.1 Methods toward their synthesis include classical protocols such as the acylation of imines, condensation of amines with aldehydes, and through the Curtius rearrangement of acyl azides as well as more modern transition metal catalyzed cross-coupling reactions with amides and activated/stereo-defined olefins.2 Another appealing route is the direct synthesis of functionally diverse enamides from readily available and inexpensive amino acids.3 Herein, we describe a noble metal-free procedure that accomplishes the direct conversion of N-acyl amino acids to enamides via a sequential radical decarboxylation and hydrogen evolution process facilitated by the cooperation of an organophotoredox catalyst and cobaloxime catalyst. This decarboxylative elimination strategy operates under neutral conditions and bypasses the need for a stoichiometric terminal oxidant and the pre-activation of the carboxylic acid moiety.4 The marriage of the decarboxylation and hydrogen evolution chemistry has allowed for a mild, operationally simple, and economical route for enamide synthesis.5 Kochi pioneered the direct conversion of carboxylic acids into olefins via decarboxylative elimination (Scheme 1A).6 However, the utility of Kochi’s elimination is limited by the requirement of a stoichiometric toxic lead oxidant, often forcing conditions, and significant limitations in scope. Additionally, these reactions tend to produce complex product mixtures.6,7 Most notably, this elimination was not successful when applied to the α-amino acid substrates of interest to us.8 In approaching the decarboxylative elimination of -amino acids, we were inspired by Sorensen’s dehydrogenation of alkanes (Scheme 1B).9 The dehydrogenation involves hydrogen atom transfer (HAT) to generate an alkyl radical followed by a second HAT reaction to generate the alkene. The need to initiate olefin formation via a hydrogen atom transfer (HAT) reaction limits the
reaction scope because it is highly dependent on C–H bond strength and thus, not very selective when many similar C–H bonds are present. Sorensen recognized this limitation and has utilized aldehydes as initiating groups that can be selectively activated due to their low C–H bond strength.10 We envisioned that olefin formation could be achieved using oxidative decarboxylation to generate a radical intermediate followed by a HAT reaction. Such use of photocatalytic decarboxylation would allow us to sitespecifically engage widely-available carboxylic acids in elimination reactions without the need to rely on differential bond strengths. Furthermore, crafting a cooperative catalytic system utilizing a photoredox catalyst and cobaloxime catalyst would allow for enamides and enecarbamates to be directly accessed from N-acyl amino acids under mild conditions without stoichiometric oxidants (Scheme 1C).
Scheme 1: A. Kochi’s Decarboxylative Elimination Pb(OAc)4/ Cu(OAc)2
COOH
Benzene, HOAc
MeO
- produces a mix of products - stoichiometric lead oxidant - doesn't opperate with amino acids OMe
B. Sorensen’s Dehydrogenation of Alkanes - not site-selective - dependent on bond strength - deuterated solvents - low yielding
TBADT COPC hv, CD3CN COPC = cobaloxime pyridine chloride TBADT = tetra-n-butylammonium decatungstate
C. Decarboxylative Elimination via Dual Catalysis (This Work) R2 R1
COOH NH R3
photoredox catalyst/ cobaloxime
R2
MeOH, Blue LED, 38 oC
R1
- readily available reactants - no stoiciometric oxidant - no pre-activation of acid
NH R3
- CO2 and H2 only byproducts - mild conditions - site-specific
The decarboxylative elimination was envisaged to be initiated via protonation of a Co(I) species by an -amino acid (pKa ~ 2, Scheme 2). It is well-documented that the basicity of Co(I) can be exploited to generate a Co(III)-hydride species (pKa = 7.7) via deprotonation of common acids.11 Thus, protonation of Co(I) will provide an -amino carboxylate. Photo-oxidation of the carboxylate, facilitated by a photoredox catalyst, followed by decarboxylation will furnish an α-amino radical.12 The reduced photoredox catalyst can in turn reduce Co(III) to Co(II), which is
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an excellent HAT acceptor that targets the weak C–H bonds adjacent to the radical center (Scheme 2).13,14 This HAT would provide the desired olefin and subsequent hydrogen evolution (HER) would complete the cycle. Ultimately the transformation would produce CO2 and H2 as the only stoichiometric byproducts and would utilize visible light as an economical and environmentally friendly energy input.15
Preliminary reactions suggested that the highest conversion towards the desired olefin product was achieved with the acridinium photocatalysts screened (>75% conversion), while poor conversion was observed with 4CzIPN (32% conversion).19 Of the acridinium catalysts that were investigated, Mes-2,7-Me2-Acr-Ph+ was found to perform the best (95% conversion) and thus was used in further screenings.20
Scheme 2: Hypothetical Mechanism
Next, the effect of catalyst loading on the decarboxylative elimination was studied. Upon doing so, it became immediately apparent that a slight excess of photocatalyst compared to cobaloxime is vital to the reaction’s success (Table 1, entries 1-3). Ultimately, a 3:5 ratio of cobalt to photocatalyst was determined to be optimal. Isolated yields were further increased through a solvent change from acetonitrile to methanol (Table 1, entry 7).
Co(III)
R
Co = cobaloxime PC = photocatalyst
O OH
H2
HN
Co(I)
R
HER
Co(III)H2 R
N H
R
R hv
Table 1: Optimization of Catalyst Loadings
O HN
PC
HAT
O
SET
PC*
R Co(III)-H
+ COOH Mes-2,7-Me2-Acr-Ph BF4 Co(dmgH)2ClPy
PC R
N H
H
R
HN
Co(II)-H
HN
HN
Boc
R
5 mol % photocatalyst Co(dmgH)2ClPy/Zn 32 W Blue LED 38 oC, 16 h, Ar
1a
Me
ClO4
NC
CN
Cz
Ph
Mes-Acr-Ph+ E1/2(P*/P-) = +2.17 V
Cz
Cz Cz
Cz = carbazole 4CzIPN E1/2(P*/P-) = +1.35 V E1/2(P-/P) = -1.21 V
O N N O
3 3 5 6 1.5 0.75 3 3 3
Cl H CoIII H N
2a
3 5 3 10 3 1.5 5 5 5
Solvent
Yieldc
MeCN MeCN MeCN MeCN MeCN MeCN MeOH Et2O DMF
29% 57%d 28% 54% 30% 15% 68% 16% 0%
aCo(dmgH)
2ClPy reduced with Zn (1 equiv.) and NaCl (3.3 equiv.) in 0.5 mL MeCN. b 0.2 mmol scale in MeCN (2 mL) under argon. c Isolated yields; products isolated as a mix of E/Z-isomers. dIsomer ratio (39:61 E:Z).
Having established the optimal catalyst loadings and solvent choice, the initial reduction of Co(III) to Co(I) was explored. Classically, this reduction had been performed with an excess of sodium borohydride (NaBH4).11a,21 However, it was hypothesized that any active reductant in the final reaction mixture would interrupt the catalysts’ performance.
Table 2: Cobalt Catalyst Optimization Boc
Co(dmgH)2ClPy
COOH
N
Ph BF4
Mes-Acr-Me+ E1/2(P*/P-) = +2.06 V E1/2(P-/P) = -0.57 V
H N
1 2 3 4 5 6 7 8 9
2a
N
N
Co(I)a Mes-2,7-Me2-Acr-Ph+BF4(mol %) (mol %)
Entry
O
To initiate studies, the elimination of N-Boc-phenylalanine (1a) was investigated using several organic photoredox catalysts combined with commercially available cobaloxime, Co(dmgH)2ClPy (Figure 1). To generate the Co(I) nucleophile, the starting Co(III) was reduced with one equivalent of zinc before being subjected to the reaction mixture. The choice in photoredox catalyst was narrowed down to the Fukuzumi family of acridiniums16 and the fluorophore, 4CzIPN17 (Figure 1). These photocatalysts appeared as the logical choices as a result of their favorable oxidation potentials (E1/2 = > +2.0 V vs. SCE for acridiniums and +1.35 V vs. SCE for 4CzIPN)18a,17 for the oxidation of amino carboxylates (E1/2 = +0.95 V vs. SCE)12e and their lower expense compared to commonly employed iridium photocatalysts. Additionally, a favorable reduction potential for the reduction of Co(III) to Co(II) (E1/2 = -0.68 V vs. SCE)18b must be considered. In this regard, 4CzIPN has a much more negative reduction potential (E1/2 = -1.21 V vs. SCE)15b while the common acridinium catalyst (Mes-Acr-Me+) has a more closely matched reduction potential (E1/2 = -0.57 V vs. SCE).18c COOH
Boc
O
R
CO2
32 W Blue LED 38 oC, 16 h, Ar
Boc
1a
Co(III)-H
H N
BF4
Mes-2,7-Me2-Acr-Ph+ E1/2(P*/P-) = +2.09 V
HN
1a
Entry O N N O
Co(dmgH)2ClPy dmgH = dimethylglyoxime E1/2 (Co(III)/Co(II)) = -0.68 V
1 2c 3 4 5 6 7
H N
32 W Blue LED, 16 h MeOH, Ar
Reductant (amt.) Zn (3 mol%) NaBH4 (2 mol%) NaCNBH3 (7.5 mol%) STAB (7.5 mol%) STAB (7.5 mol%) STAB (7.5 mol%) STAB (7.5 mol%)
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Co(I)
Co(I) (3 mol%) Mes-2,7-Me2-Acr-Ph+BF4- (5 mol%) additive 2 (7.5 mol%)
Boc
Figure 1: Potential Cooperative Catalysts Screened
reductant additive 1 reflux 50 min. MeOH, Ar
Additive 1 (amt.) NaCl (10 mol%) Na2CO3 (1 mol%) Na2CO3 (1 mol%)
Boc
2a
Additive 2 (7.5 mol%) H 2O H 2O
Yieldb 68% 20% 38% 52% 70% 66% 82%
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ACS Catalysis aGeneral conditions: Co(dmgH) ClPy (3 mol%) and reductant 2 refluxed in methanol (0.5 mL) for 50 min. The reduced cobalt catalyst solution was added to N-Boc-phenylalanine (0.2 mmol) and Mes-2,7-Me2-Acr-Ph+ (5 mol%) then irradiated with blue LEDs for 16 h under argon. bIsolated yields; isolated as a mix of E/Z-isomers. cReduction performed in acetonitrile.
Thus, the choice in reductant and the amount used in the initial catalyst reduction could impact the success of the elimination reaction. In addition to zinc, NaBH4, sodium cyanoborohydride (NaCNBH3), and sodium triacetoxyborohydride (STAB) were screened (Table 2, entries 1-4). Apart from zinc, STAB provided the highest isolated yield. The use of a catalytic amount of sodium carbonate in the cobaloxime reduction with STAB as well as the addition of water to the reaction solvent further increased the yield (Table 2, entries 5-6). Upon utilizing these additives in conjunction, an 82% isolated yield was achieved (Table 2, entry 7). In addition to optimization studies, control experiments were also conducted. Only a trace amount of alkene was observed in the absence of photocatalyst and no product was observed in the absence of the cobalt catalyst. While the reaction could be carried out under air, a decrease in yield to 60% was observed under aerobic conditions. Finally, the reaction was found to reach completion in 16 hours with no change in yield upon increasing the irradiation time to 24 hours. With optimal conditions in hand, a variety of N-protected amino acids were investigated for the direct synthesis of enamides and enecarbamates (Table 3). Derivatives of phenylalanine were found to be useful substrates for the elimination (2a-2i). Interchanging tert-
Table 3: Scope of N-Acyl Amino Acids R2 R1
R3
+
Mes-2,7-Me2-Acr-Ph BF4 (5 mol%) R2 Co(dmgH)2ClPy (3 mol%) MeOH, H2O (7.5 mol%), Ar R1 32 W Blue LED, 16 h
COOH
HN
-
R4
1a-x
H N
R
2a R = Boc; 82%, (65:35) 2b R = Ac; 85%, (65:35) Cl
H N
H N
H N R
2j R = Ac; 72%, (82:18) 2k R = Boc; 41%, (71:29) 2l R = Cbz; 52%, (71:29)
X 2d X = CN; 85%, (81:19) 2e X = F; 70%, (69:31) 2f X = Cl; 75%, (71:29) 2g X = OMe; 58%, (67:33)
N H
R
2m R = Ac; 90%, (85:15) 2n R = Boc; 34%, (80:20)
O N H
Ac
Boc
2i 71%, (90:10)
2h 71%, (67:33) H N
2c 77%, (66:34)
Boc
H N
N Boc
O
R
2s R = Ac; 80%, 75:25 2t R = Boc; 24%, >99:1
Cbz
Boc
O
2q 73%, 64:36e
N H
H N
O
O
N H
Ac
2o 90%
O O
2p 66%
O
HN R4
2a-x
H N
O
R3
H N 2u 77%, (76:24)
2r 45%, 67:33 H N
Ac
Ac N H 2v 51%, (10:90)e
aReactions were run on 0.2 mmol scale under argon. bCobalt catalyst was reduced with STAB (7.5 mol%) and Na2CO3 (1 mol%) in MeOH (0.5 mL) at reflux for 50 min and added via syringe to the reaction mixture. cAll yields reported are isolated
yields. dIsomer ratios were determined by 1H NMR. eMajor isomer determined by NOESY. butyloxycarbonyl (Boc) and acetyl protecting groups provided similar yields and E:Z selectivity (2a, 2b). This allows a simple dipeptide to be utilized in the elimination chemistry (2c). Additional functionalities on the aryl substituent in the para and ortho positions were also tolerated and having an electronwithdrawing substituent in the para-position provided a slight increase in yield and E-selectivity. Conversely, an electrondonating para substituent lead to a decrease in yield (2d-2g). Amino acids other than phenylalanine derivatives provided considerably higher yields when the nitrogen was acylated rather than substituted with a carbamate protecting group (2i-2n), and unprotected amino acids failed to undergo the reaction. Aside from the protecting group influences, various aliphatic side chains, including those with ester and amine functionalities, led to good to excellent yields of enamides. Additionally, trisubstituted alkenes (2o-2q) could also accessed through decarboxylative elimination. In addition to the success this protocol had with a variety of amino acids, the decarboxylative elimination also proved to be scalable. The scalability of this protocol is demonstrated by the 1 mmol reaction with amino acid (1a) (Scheme 3).22 Scheme 3: Scale-up Decarboxylative Elimination
COOH HN Boc (1a) 1 mmol
Co(I) (3 mol%) Mes-2,7-Me2Acr-Me+ ClO4- (5 mol%) MeOH (10 mL), H2O (7.5 mol%) 32 W Blue LED, 16 h, Ar
H N
Boc
(2a) 83% yield, 54:46 E:Z
To better understand the nature of the observed geometric ratios of products, several additional experiments were conducted. It was speculated that photo-isomerization of the alkenes could be a factor, either through an electron transfer or energy transfer from the photocatalyst to the alkene. Photoisomerizations of this nature have been described by Weaver23 using iridium photoredox catalysts but have not been previously reported with the acridiniums. To explore this, the E- and Z- isomers of aspartic acid derivative (2n) were independently subjected to the photocatalyst and irradiated in acetonitrile. Indeed, isomerization was observed in each case, producing a steady-state mixture of ca. 45:55 E:Z (Scheme 4A).24,25 The same isomerization does not occur upon irradiation in the absence of a photocatalyst or at elevated temperature (50 oC). Taken together, these observations support a hypothesis that the product E:Z ratios represent the photostationary state of each product under the reaction conditions. Further mechanistic information was provided by the reaction of N-Boc phenylalanine in CD3OD in a sealed NMR tube (Scheme 4B). Analysis of the crude reaction mixture revealed the formation of H-D and H2 in a 6:1 ratio. The H-D presumably results from coupling of the exchangeable acid proton (Boc-NHCHBnCO2D) with the H-atom abstracted in the HAT reaction. Since the exchange of the N-H proton with deuterated solvent is slow under the reaction conditions, the H-D hydrogen could originate from either the N-H or C-H positions -to the radical. We favor the pathway involving HAT from the C-H bond because we see no evidence for imine formation. Moreover, subjecting a tertiary amino acid, which lacks an N-H bond, to the standard reaction conditions results in product formation (Scheme 4C). Interestingly, the N-Me reactant exhibits a high selectivity for the E-olefin.
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conditions, all of which are seen in related attempts to achieve this transformation. Further explorations into the reaction mechanism and controlling the E/Z selectivity are currently under investigation in our lab.
Scheme 4: Mechanistic Investigations A. Photo-isomerization
ASSOCIATED CONTENT Ph
HN
Boc
Supporting Information
(5 mol%)
BF4
HN
32 W Blue LED, 16 h MeCN, Ar
2a (Z)
H N
N
Ph
Boc
N
45:55 E:Z
(5 mol%)
BF4
HN
32 W Blue LED, 16 h MeCN, Ar
2a (E)
Experimental procedures, 1H, 13C NMR spectra, and characterization data for all new compounds. The Supporting Information is available free of charge on the ACS Publications website.
Boc
AUTHOR INFORMATION
Boc
43:57 E:Z
Corresponding Author
B. Reaction Monitored by 1H NMR Spectroscopy HN
COOD
Co(I)/Acr+
Boc
CD3OD Blue LED
1a
H N
[email protected] Boc
Notes
2a
The authors declare no competing financial interests.
65% conversion
ACKNOWLEDGMENT
C. Reaction with Tertiary Amino Acid
Me
N
COOH
Co(I)/Acr+
Boc
CH3OH Blue LED
1w
Me N Boc
2w
52% E/Z > 95:5
The utility of enecarbamate scaffolds was also demonstrated (Scheme 5). These scaffold are known to serve as nucleophiles leading to additions β to the amine.1 This mode of nucleophilic attack or in situ tautomerization results in imine formation which allows (2a) to react as an electrophile thus providing the opportunity for diversification α to the amine. Both nucleophilic and electrophilic reactivities of (2a) are exemplified by the set of reactions performed. As with many reactions with enamide and enecarbamate substrates, these reactions are able to proceed with both the E- and Z- isomers to provide one product derived from a common intermediate. In cases where a single geometric isomer is desired, the photo-isomerization reported by Weaver23a can be exploited to enrich one geometric isomer. As such, the isomers of 2a were separated and the E- isomer was subjected to the isomerization conditions to provide an the Z- olefin in good yield with high selectivity (4:96 E:Z). Scheme 5: Reactions with Enecarbamate (2a) H N
(3a) 62% yield (over 2 steps)
O 26
Hydrolysis
COOH HN
Boc
on 4h cti H 4, H, du Re , NaB iPrO /C H, Pd CO 2 CH 3
1M HCl aq. 57 oC, ~16 h
H N
Co(I)/Acr+
Boc
2a 82% yield (65:35 E:Z)
Blue LED
E-isomer, Isomerization23a Ir(ppy)3 Blue LED, 30 oC 36 h
HN
Friedel-Crafts1b 1-H-indole, phosphoric acid cat. 50 oC, ~16 h
Bro m NB inatio S n 1h 30 o , NEt 3 C, ~16 h
82% yield (4:96 E:Z) (over 2 steps)
Boc
(3b) 81% yield (over 2 steps)
H N
Boc
HN (3c) 69% yield (over 2 steps)
Br
H N
Boc
(3d) 29% yield (over 2 steps)
Boc
In conclusion, a mild and direct decarboxylative elimination of readily available amino acids for the production of enamides and enecarbamates has been realized. This protocol bypasses the use of stoichiometric oxidants, toxic and expensive reagents, and harsh
We thank the National Science Foundation (CHE-1800147) and the Kansas Bioscience Authority Rising Star program for financial support. Support for the NMR instrumentation was provided by NSF Academic Research Infrastructure Grant No. 9512331, NIH Shared Instrumentation Grant No. S10RR024664, and NSF Major Research Instrumentation Grant No. 0320648. X-ray analysis was made possible through an NSF-MRI grant CHE-0923449.
REFERENCES 1. (a) Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.; Maleczka, J.; R. E.; Smith III, M. R. Outer-Sphere Direction in Iridium CH Borylation. J. Am. Chem. Soc. 2012, 134, 11350-11353. (b) Terada, M.; Sorinmachi, K. Enantioselective Friedel-Crafts Reaction of Electron-Rich Alkenes Catalyzed by Chiral Brønsted Acid. J. Am. Chem. Soc. 2007, 129, 292-293. (c) Wu, P.; Lin, D.; Lu, X.; Zhou, L.; Sun, J. Trimethylchlorosilane-Promoted Aza-Mannich Reaction of Enecarbamates and Aldimines. Tetrahedron Lett. 2009, 50, 7249-7251. (d) Fürstner, A.; Dierkes, T.; Thiel, O. R.; Blanda, G. Total Synthesis of (-)Salicylihalamide. Chem. Eur. J. 2001, 7, 5286-5298. (e) Galinis, D.; McKee, T.; Pannell, L.; Cardellina, J.; Boyd, M. Lobatamides A and B, Novel Cytotoxic Macrolides from Tunicate Aplidium lobatum. J. Org. Chem. 1997, 62, 8968-8969. (f) Suzumura, K.; Takahashi, I.; Matsumoto, H.; Nagai, K.; Setiawan, B.; Rantioamodjo, R.; Suzuki, K.; Nagano, N. Structural Elucidation of YM-75518, A Novel Antifungal Antibiotic Isolated from Pseudomonas sp. Q38009. Tetrahedron Lett. 1997, 38, 75737576. (g) Kim, J.; Shin-ya, K.; Furihata, K.; Hayakawa, Y.; Seto, H. Oximidines I and II: Novel Antitumor Macrolides from Pseudomonas sp. J. Org. Chem. 1999, 64, 153-155. (h) Ferreira, P. M. T.; Monteiro, L. S.; Pereira, G.; Ribeiro, L.; Sacramento, J.; Silva, L. Eur. J. Org. Chem. 2007, 35, 5934-5949. 2. (a) Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J. Late Transition Metal-Catalyzed Hydroamination and Hydroamidation. Chem. Rev. 2015, 115, 2596-2697. (b) Matsubara, R.; Kobayashi, S. Enamides and Enecarbamates as Nucleophiles in Stereoselective C-C and C-N BondForming Reactions. Acct. Chem. Res. 2008, 41, 292-301. 3. Decarbonylative strategies towards enamide synthesis from amino acids: (a) Garcίa-Reynaga, P.; Carrillo, A. K.; VanNieuwenhze, M. S. Decarbonylative Approach to the Synthesis of Enamides from Amino Acids: Stereoselective Synthesis of the (Z)-Aminovinyl-D-Cysteine Unit of Mersacidin. Org. Lett. 2012, 14, 1030-1033. (b) Min, G. K.; Hernández, D.; Lindhardt, A. T.; Skrydstruo, T. Enamides Accessed from Aminothioesters via a Pd(0)-Catalyzed Decarbonylative/β-Hydride Elimination Sequence. Org. Lett. 2010, 12, 4716-4719. 4. Activation of acids for decarboxylation with redox-active groups: (a) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.; Pan, C-M.;
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ACS Catalysis Gianatassio, R.; Schmidt, M.; Eastgate, M. D.; Baran, P. S. Practical NiCatalyzed Aryl-Alkyl Cross-Coupling of Secondary Redox-Active Esters. J. Am. Chem. Soc., 2016, 138, 2174-2177. (b) Tlahuext-Aca, A.; Candish, L.; Garza-Sanchez, R. A.; Glorius, F. Decarboxylative Olefination of Activated Aliphatic Acids Enabled by Dual Organophotoredox/Copper Catalysis. ACS Catal., 2018, 8, 1715-1719. Direct decarboxylative elimination with stoichiometric oxidant: (c) Wu, S-W.; Liu, J-L.; Liu, F. Metal-Free Microwave-Assisted Decarboxylative Elimination for the Synthesis of Olefins. Org. Lett., 2015, 18, 1-3. Recent Reviews on decarboxylative functionalization: (d) Mondal, S.; Chowdhury, S. Recent Advances on Amino Acid Modifications via C-H Functionalization and Decarboxylative Functionalization Strategies. Adv. Synth. Catal, 2018, 360, 1884-1912. (e) Xuan, J.; Zhang, Z-G.; Xiao, W-J. Visible-Light-Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives. Angew. Chem. Int. Ed. 2015, 54, 15632-15641. (f) Angnes, R. A.; Li, Z.; Correia, C. R. D.; Hammond, G. B. Recent Synthetic Additions to the Visible Light Photoredox Catalysis Toolbox. Org. Biomol. Chem., 2015, 13, 9152-9167. 5. During review of this manuscript, a similar process for decarboxylative elimination was published: Sun, X.; Chen, J.; Ritter, T. Catalytic Dehydrogenative Decarboxyolefination of Carboxylic Acids. Nat. Chem. 2018. https://doi.org/10.1038/s41557-018-0142-4 6. (a) Sheldon, R. A.; Kochi, J. K. Oxidative Decarboxylation of Acids by Lead Tetraacetate. Org. React. 1972, 19, 279-421. (b) Kochi, J. K.; Bemis, A.; Jenkins, C. L. Mechanism of Electron Transfer Oxidation of Alkyl Radicals by Copper(III) Complexes. J. Am. Chem. Soc. 1968, 90, 4616−4625. 7. (a) McGuirk, P. R.; Collum, D. B. Total Synthesis of (+)-Phyllanthocin. J. Am. Chem. Soc. 1982, 104, 4497-4497. (b) Jensen, N. P.; Johnson, W. S. A Three-Step Synthesis of Fichtelite from Abietic Acid. J. Org. Chem. 1967, 32, 2045-2046. (c) McMurry, J. E.; Blaszczak, L. C. New Method for the Synthesis of Enones. Total Synthesis of (+-)-Mayurone and (+-)Thujopsadiene. J. Org. Chem. 1974, 39, 2217-2222. 8. Attempted enamide synthesis with Kochi method: (a) Needles, H. L.; Ivanetich, K. Decarboxylation of N-Acetylamino-Acids with Lead TetraAcetate in N’Ndimethylformamide. Chem. Ind. 1967, 14, 581. Kochi method used for acetoxylation and subsequent elimination: (b) Wang, X.; Porco, J. A. Jr. Modification of C-Terminal Peptides to form Peptide Enamides: Synthesis of Chondriamides A and C. J. Org. Chem., 2001, 66, 8215-8221. Kochi-like acetoxylation with cobalt and stoichiometric oxidant: (c) Xu, K.; Wang, Z.; Zhang, J.; Yu, L.; Tan, J. Cobalt-Catalyzed Decarboxylative Acetoxylation of Amino Acids and Arylacetic Acids. Org. Lett., 2015, 17, 4476-4478. 9. West, J. G.; Huang, D.; Sorensen, E. J. Acceptorless Dehydrogenation of Small Molecules Through Cooperative Base Metal Catalysis. Nat. Commun. 2015, 6, 10093. 10. Acrams, D. J.; West, J. G.; Sorensen, E. J. Toward a Mild Dehydroformylation Using Base-Metal Catalysis. Chem. Sci., 2017, 8, 1954-1959. 11. Nucleophilicity of Cobaloxime(I): (a) Schrauzer, G. N.; Deutsch, E. Reactions of Cobalt(I) Supernucleophiles. The alkylation of Vitamin B12s, Cobaloxime(I), and Related Compounds. J. Am. Chem. Soc. 1969, 91, 3341-3350. (b) Natali, M. Elucidating the Key Role of pH on Light-Driven Hydrogen Evolution by a Molecular Cobalt Catalyst. ACS Catal. 2017, 7, 1330-1339. 12. Other select examples of photoredox facilitated decarboxylation of carboxylates: (a) Lang, S. B.; Cartwright, K. C.; Welter, R. S.; Locascio, T. M.; Tunge, J. A. Photocatalytic Aminodecarboxylation of Carboxylic Acids. Eur. J. Org. Chem. 2016, 20, 3331-3334. (b) Noble, A.; McCarver, S. J.; MacMillan, D. W. Merging Photoredox and Nickel Catalysis: Decarboxylative Cross-Coupling of Carboxylic Acids with Vinyl Halides. J. Am. Chem. Soc. 2015, 137, 624-627. (c) Ventre, S.; Petronijevic, F. R.; MacMillan, D. W. Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis. J. Am. Chem. Soc. 2015, 137, 5654-5657. (d) Lang, S. B.; O’Nele, K. M.; Tunge, J. A. Decarboxylative Allylation of Amino Alkanoic Acids and Esters via Dual Catalysis. J. Am. Chem. Soc. 2014, 136, 13606-13609. (e) Zuo, Z.; MacMillan, D. W. C. Decarboxylative Arylation of α-Amino Acids via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug Pharmacophore. J. Am. Chem. Soc. 2014, 136, 5257-5260. (f) Miyake, Y.; Nakajima, K.; Nishibayashi, Y. Visible
Light-Mediated Oxidative Decarboxylation of Arylacetic Acids into Benzyl Radicals: Addition to Electron-Deficient Alkenes by Using Photoredox Catalysis. Chem. Commun. 2013, 49, 7854-7856. 13. Cobaloxime HAT: (a) Li, G.; Pulling, M. E.; Estes, D. P.; Norton, J. R. Evidence for Formation of a Co-H Bond from (H2O)2Co(dmgBF2)2 Under H2: Application to Radical Cyclizations. J. Am. Chem. Soc. 2012, 134, 14662–14665. C-H bonds adjacent to radicals dissociation enthalpy: (b) Zhang, X.-M. Homolytic Bond Dissociation Enthalpies of the C-H Bonds Adjacent to Radical Centers. J. Org. Chem. 1998, 63, 1872–1877. 14. Co(II) and radical intermediates could reversibly form Co(III)-C species: Halpern, J. Determination and Significance of Transition MetalAlkyl Bond Dissociation Energies. Acc. Chem. Res., 1982, 15, 238-244. 15. (a) Dempsey, J. L.; Brunschwig, B. S.; Winkler, J. R.; Gray, H. B. Hydrogen Evoluton Catalyzed by Cobaloximes. Acc. Chem. Res. 2009, 42, 1995-2004. (b) Estes, D. P.; Grills, D. C.; Norton, J. R. The Reaction of Cobaloximes with Hydrogen: Products and Thermodynamics. J. Am. Chem. Soc. 2014, 136, 17362-17365. (c) Artero, V.; Chavarot-Kerlidou, M.; Fontecave, M. Splitting Water with Cobalt. Angew. Chem. Int. Ed. 2011, 50, 7238-7266. 16. (a) Fukuzumi, S.; Kotani, H.; Ohkubo, K.; Ogo, S.; Tkachenko, N. V.; Lemmetyinen, H. Electron-Transfer State of 9-Mesityl-10methylacridinium Ion with a Much Longer Lifetime and Higher Energy Than That of the Natural Photosynthetic Reaction Center. J. Am. Chem. Soc. 2004, 126, 1600-1601. (b) For a review on organic photoredox catalysis: Romero, N. A.; Nicewicz, D. A. Organic Photoredox Catalysis. Chem. Rev. 2016, 116, 10075-10166. 17. Luo, J.; Zhang, J. Donor-Acceptor Fluorophores for Visible-LightPromoted Organic Synthesis: Photoredox/Ni Dual Catalytic C(sp3)-C(sp2) Cross-Coupling. ACS Catal. 2016, 6, 873-877. 18. All potentials listed were obtained in acetonitrile and versus saturated calomel electrode (SCE): (a) Romero, N. A.; Margrey, K. A.; Tay, N. E.; Nicewicz, D. A. Site-Selective Arene C-H Amination via Photoredox Catalysis. Science. 2015, 349, 1326-1330. (b) Hu, X.; Brunschwig, B. S.; Peters, J. C. Electrocatalytic Hydrogen Evolution at Low Overpotentials by Cobalt Macrocyclic Glyoxime and Tetraimine Complexes. J. Am. Chem. Soc. 2007, 129, 8988-8998. (c) DiRocco, D. A. Acridinium-Based Photocatalysts: A Sustainable Option in Photoredox Catalysis. J. Org. Chem. 2016, 81, 7244-7249. (d) Fukuzumi, S.; Ohkubo, K.; Tomoyoshi, S. Long-Lived Charge Separation and Applications in Artificial Photosynthesis. Acc. Chem. Res. 2014, 47, 1455-1464. 19. Determined by GCMS analysis; Reactions were performed using NBoc-phenylalanine (0.2 mmol), photocatalyst (5 mol%), Cobaloxime (3mol%), in MeCN. 20. Mes-Me2-Acr-Ph+ first appeared in hydrofluoronation reaction: Wilger, D. J.; Grandjean, J. M.; Lammert, T. R.; Nicewicz, D. A. The Direct AntiMarkovnikov Addition of Mineral Acids to Styrenes. Nature Chemistry. 2014, 6, 720-726. 21. Bulkowski, J.; Cutler, A.; Dolphin, D.; Silverman, R. B. Bis[2,3Butanedione Dioximato (1-)] Cobalt Complexes. Inorg. Synth. 1980, 20, 127-134. 22. Photocatalyst utilized for scale-up reaction utilized Mes-2,7-Me2-AcrMe instead of Mes-2,7-Me2-Acr-Ph. 23. (a) Singh, K.; Staig, S. J.; Weaver, J. D. Facile Synthesis of Z-Alkenes via Uphill Catalysis. J. Am. Chem. Soc. 2014, 136, 5275-5278. (b) Singh, A.; Fennell, C. J.; Weaver, J. D. Photocatalyst Size Controls Electron and Energy Transfer: Selectable E/Z Isomer Synthesis via C-F Alkenylation. Chem. Sci. 2016, 7, 6796-6802. 24. The isomerization also proceed to ~80:20 E:Z in methanol, however, degradation also resulted. 25. For isomerization experiments, 0.04 mmol of each isomer was used and isomerizations were completed under typical reaction set-up as described in SI. 26. Tran, A. T.; Huynh, V. A.; Friz, E. M.; Whitney, S. K.; Cordes, D. B. A General Method for the Rapid Reduction of Alkenes and Alkynes using Sodium Borohydride, Acetic Acid, and Palladium. Tetrahedron Lett. 2009, 50, 1817-1819.
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