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Letter
Remote Allylation of Unactivated C(sp3)–H Bonds Triggered by Photogenerated Amidyl Radicals Bin Xu, and Uttam K Tambar ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b00563 • Publication Date (Web): 16 Apr 2019 Downloaded from http://pubs.acs.org on April 16, 2019
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ACS Catalysis
Remote Allylation of Unactivated C(sp3)–H Bonds Triggered by Photogenerated Amidyl Radicals Bin Xu and Uttam K. Tambar* Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States. ABSTRACT: The allylation reaction is a highly versatile transformation in chemical synthesis. While many elegant direct C(sp2)–H allylation reactions have been developed, the direct allylation of unactivated C(sp3)–H bonds is underdeveloped. By applying photoredox catalysis and a [1,5]-HAT process, herein we report a direct allylation of unactivated C(sp3)‒H bonds. This photocatalyzed transformation is tolerant of several functional groups in the amide and allylic chloride substrates. Various allyl-substituted amide products were obtained with good yields and high -selectivity.
KEYWORDS: Allylation, C(sp3)‒H, photocatalysis, -selectivity, radical, [1,5]-HAT. The allylation reaction is one of the most fundamental and powerful transformations to construct new C–C bonds in organic synthesis.1‒3 The allylic moiety in the product enables further transformations due to a versatile double bond that can be manipulated synthetically. Traditional allylations include nucleophilic allylation of carbonyl compounds and imines,1a allylic substitution of carbanions,2 transition-metal-catalyzed decarboxylative allylations1b and allylic cross-couplings of aromatic halides.3 Among these methods, pre-installed functional groups are required in the starting materials.
1,5-HAT process triggered by photoredox-generated amidyls, various allyl-substituted amides are obtained with good yields, high -selectivity, and high functional group tolerance. Scheme 1. Allylation Reactions of C–H Bonds
To pursue higher reaction efficiency and atom economy, the direct functionalization of C–H bonds represents one of the most intriguing and advanced technologies in synthetic chemistry.4 Many successful direct allylation reactions of aromatic and vinylic C(sp2)– H bonds have been disclosed,1d which allows for the rapid generation of molecular complexity (Scheme 1A). However, examples of C(sp3)–H allylation are rare. Current achievements in this field are limited to activated C(sp3)–H bonds,5 such as allylic and dibenzylic C(sp3)–H bonds, or C(sp3)–H bonds adjacent to carbonyl groups and heteroatoms (Scheme 1B). The direct allylation of unactivated C(sp3)–H bonds is still underdeveloped. Recently, radical mediated hydrogen-atom transfer (HAT) has provided an efficient and mild path to cleave unactivated C(sp3)–H bonds that allows for subsequent functionalizations.6 Breakthroughs mediated by Nitrogen7 and Oxygen-centered8 radicals have been achieved by photocatalysis. Flechsig and Wang recently reported an allylation of sp3 C–H bonds with allyl sulfones activated by electron-withdrawing groups via photocatalytic fragmentation of pre-functionalized aryloxy amides (Scheme 1C).9 Herein, we report a direct allylation of unactivated C(sp3)–H bonds in unfunctionalized amides with simple allylic chlorides (Scheme 1D). By applying a
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ACS Catalysis
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Me A. Allylation of C(sp 2)-H Bonds R3
DG H
R1
+
LG
Me cat. [M] M = Ru, Pd, Rh, Re, Ir, Co, Mn, Ni, Fe, Cu
2 mol% [Ir](dF-CF 3) 10 mol% Ni(COD) 2 11 mol% L1 2.0 equiv K 3PO 4
+
R2
R2
TFA
1a
R1
DG
N H
R3
n-Bu
Cl
LG = OH, OAc, OCO 2R, Halogens, etc.
R2
R3
+
H
cat. [Ir]
X
R *
Krische, Zhang
O
R2
R3
+
X
R1
cat. [Pd] / [Ir]
R2
*
R3
O
Ph
N OAr
Me
O
eosin Y Green LEDs
Me
Ph
Me
N H
Me
Ar = 2,4-dinitrophenyl
D. Allylation of unactivated Bonds in Unfunctionalized Amides with Simple Allyl Chlorides (This Research) R3 H Cl Photocatalyzed -Allylation R3 NHR + NHR R1 R1 R2 R2 R1
Cl H
N R2 R
1,5-HAT
R1
R3
NH R2 R
As a model reaction for the direct allylation of unactivated C(sp3)–H bonds, trifluoroacetamide 1a and allylic chloride 2a were irradiated in the presence of a [Ir(dF(CF3)ppy)2(dtbpy)]PF6 photocatalyst, Ni(COD)2, bisoxazoline L1 and K3PO4 under 34W blue LED for 48 hours to afford the C–H allylation product 3aa in 72% isolated yield and high -selectivity (Table 1, entry 1).10 The corresponding allylic bromide and iodide generated considerable amounts of the undesired N–H allylation Table 1. Reaction Conditions for -Allylationa
O
O
N
N
L1
R
R
N
O N
F
F 3C
L2
N
L3: R = t-Bu L4: R = MeO
N
Yieldb (3aa, %)
Yieldb (3aa', %)
76 (72 c)
0
instead of 2a
28
52
instead of 2a
0
85
Variation From Standard Conditions
1a
none
2
Br
3
I
C(sp3)-H
Photocatalysis
F F
N
tBu
3aa'
N-H allylation
PF 6-
Ir
Entry
EWG
SO2Ph EWG
+
TFA
[Ir(dF(CF 3)ppy)2(dtbpy)]PF 6
C. Allylation of unactivated C(sp3)-H Bonds in Aryloxy Amides with Electron-Deficient Allyl Sulfones (Flechsig & Wang, 2019) O
N Me
+
N N
Ooi, Hartwig, Snaddon
3aa
+ Me
blue LED (34W), MeCN, 25 oC, 48 h
F
tBu
N
R1 H
TFA
N H
n-Bu
F 3C R3
sp3 C-H allylation
2a OH
OH
Me Me
B. Allylation of activated C(sp3)-H Bonds R1
n-Bu
n-Bu
4d
No blue LED
0
8
5d
No K 3PO 4
0
0
6d
No Ir catalyst
0
12
7d
[Ir(ppy) 3] instead of Ir catalyst
0
10
8d
[Ru(bpy) 3]2+ instead of Ir catalyst
0
8
9
No Ni(COD) 2 and no L1
48
0
10
NiBr 2 (CH 2OMe) 2 instead of Ni(COD) 2
36
0
11
L2 instead of L1
38
0
12
L3 instead of L1
58
0
13
L4 instead of L1
66
0
14
no L1
34
0
a Reaction conditions: [Ir(dF(CF )ppy) (dtbpy)]PF 3 2 6 (2 mol%), Ni(COD)2 (10 mol%), L1 (11 mol%), 1a (0.1 mmol), 2a (0.15 mmol), K3PO4 (0.2 mmol), MeCN (0.5 mL), 34 W blue LED, 48 h. Conversion was >95% by 1H NMR. b 1H NMR yields with 1,3,5-tribromobenzene as internal standard. c Isolated yield. d Conversion was 0-15% by 1H NMR.
product 3aa’ (entries 2 and 3), which is most likely formed via nucleophilic substitution between the amide and the more electrophilic allylic halides. We did not observe any C–H allylation product in the absence of blue LED excitation (entry 4), K3PO4 (entry 5), or [Ir(dF(CF3)ppy)2(dtbpy)]PF6 (entry 6). The use of other photoredox catalysts, such as [Ir(ppy)3] (entry 7) and [Ru(bpy)3]2+ (entry 8),11 suppressed the formation of the desired product. Although the nickel catalyst was not necessary for product formation (entry 9, 48% yield), the yield of 3aa was improved in the presence of nickel
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ACS Catalysis catalyst (entry 1, 76%). Interestingly, the effect of the nickel catalyst on the efficiency of the reaction was sensitive to the structure of the nickel complex (entries 10-13). Other bidentate ligands L2-L4 resulted in lower yields of 3aa (entries 11-13). Additionally, the absence of L1 resulted in a significant loss in yield (entry 14). The combination of Ni(COD)2 and L1 was therefore deemed optimal for product formation. Table 2. Substrate Scopea
R3
H R1 R2
2 mol% [Ir](dF-CF3) 10 mol% Ni(COD)2 11 mol% L1 4 R 2.0 equiv K PO 3 4
NHTFA + Cl
R3
MeCN, blue LED 25 oC, 48 h
2
1
R4
R1 R2 3
(A)
n-Bu
n-Bu
n-Bu NHTFA Me Me Me 3aa, 72% yield
NHTFA
NHTFA Me
Me Me
Me Me 3ca, 68% yield
3ba, 62% yield
n-Bu
n-Bu
n-Bu NHTFA
NHTFA
NHTFA
Me
3fa, 70% yield
3ea, 72% yield
3da, 52% yield
n-Bu
n-Bu NHTFA
Me
NHTFA
n-Bu NHTFA
NHTFA OTBS
Me 3ga, 38% yield
3ha, 40% yield
3ia, 58% yield
Me n-Bu
n-Bu
NHTFA NHTFA
Me Me
NHTFA Me Me NHBoc
n-Bu 3ka, 64% yield
3ja, 46% yield
3la, 68% yield
a Reaction conditions: [Ir(dF(CF )ppy) (dtbpy)]PF 3 2 6 (2 mol%), Ni(COD)2 (10 mol%), L1 (11 mol%), 1a (0.1 mmol), 2a (0.15 mmol), K3PO4 (0.2 mmol), MeCN (0.5 mL), 34 W blue LED, 48 h.
We evaluated the scope of the -selective C−H allylation with various amides 1a‒l and allylic chloride 2a (Table 2A). Amides bearing a methine carbon on the position were examined (1a-1f). The reaction exhibited good tolerance to different hydrocarbon substituents, such as methyl (3aa, 3ba, 3da), ethyl (3ca), n-butyl (3ca), neopentyl (3ba), phenyl (3da), cyclopentyl (3ea), and cyclohexyl (3fa). Amides with methylene-carbons were also tested (3ga–3ja). Although only moderate yields were obtained (38–58%), the -selectivity was retained. To further demonstrate the synthetic potential of the reaction, we employed amide substrates derived from natural products, such as 1k from (L)-menthol and 1l from (S)-leucine. In both instances, the desired -allylation products 3ka and 3la were obtained in satisfying yields.12 Remote sp3 C‒H allylations with various allylic chlorides 2b-2n were also investigated (Table 2b). Substrates bearing aliphatic substitution at the internal C2-position of the allylic system exhibited good tolerance to functional groups, such as an aromatic ring (3ab), trimethylsilane (3ac), TBS-protected alcohol (3ad), and alkene (3ae). The steric bulk of the C2-substituent did not influence the yield or -selectivity of product formation (3af-3ah). Even a sterically demanding adamantyl group afforded the desired product 3ah in 64% yield. Various aromatic C2-substituents were also examined (3ai-3am). The desired -selective C–H allylation products were obtained in synthetically useful yields (62–76% yield). A substrate with an electron-withdrawing group was also tested. With an ester group on the C2-position, allylic chloride 2n afforded the desired -allylation product 3an in 38% yield, with significant amounts of the N-allylation byproduct (47% yield).13 Scheme 2. Deuterium Labeled Experiments
(B) Me Si Me Me
OTBS
NHTFA Me Me 3ac, 66% yield
NHTFA Me Me 3ab, 72% yield
Ph 2
Cl
1
4
3
+ Me
Me Me Me 3ae, 66% yield
D D
NHTFA Me Me 3ad, 64% yield
Et NHTFA
A. Allylation of deuterated allylic chloride
NHTFA Me Me 3af, 78% yield
2 mol% [Ir] catalyst 10 mol% Ni(COD) 2 11 mol% L7 2.0 equiv K 3PO 4
NHTFA Me
NHTFA Me Me 3ag, 70% yield
NHTFA Me Me 3an, 38% yield
D
Ph
NHTFA
3
Me Me D
1
6 +
D
NHTFA
1
2 3
Optimal result: No Ni(COD) 2/L1:
Ph
Cl
NHTFA Me Me 3ai, R = H, 3aj, R = Me, 3ak, R = Ph, 3al, R = OPh, 3am, R = F,
D
1a
D D
NHTFA
CO2Bn
2
Me Me
7
72% yield, n6 : n7 = 88% : 12% 45% yield, n6 : n7 = 88% : 12%
B. Isomerization of deuterated allylic chloride
R
Me Me 3ah, 64% yield
MeCN, blue LED 25 oC, 36 h
Ph
70% yield 68% yield 62% yield 64% yield 76% yield
4
D D
Ph
Cl
D
Ph
Radical pair
Blue LED, MeCN, 25 oC, 36 h and other conditions
Cl D 5 Ratio of n 4 : n5
1. 2 mol% [Ir] catalyst
77% :
23%
2. 2 mol% [Ir] catalyst & 10 mol % Ni(0) complex
89% :
11%
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Although we do not fully understand the role of the Ni(0) complex in improving the yield of the photocatalyzed allylation of unactivated C(sp3)-H bonds, we conducted a series of deuterium-labeled experiments to gain some insight (Scheme 2). When deuterated substrate 4 ((3-chloroprop-1-en-2-yl-3,3-d2)benzene) was used under optimal conditions (Scheme 2A), the ratio of products 6:7 was the same in the presence or absence of the Ni(0) complex, which suggests that the Ni(0) complex did not significantly alter the reaction pathway. Based on these observations, we can rule out the formation of a Ni(II) (3)allyl--complex from allylic chloride, which would have formed equal amounts of 6 and 7. We also propose the Ni(0) complex improves the yield of the photocatalyzed allylation by stabilizing the allylic chloride substrate. The high ratio of 6:7 (88:12) is consistent with a C–C bond forming mechanism via radical addition to the double bond of the allylic chloride. The formation of small amounts of allylation product 7 can be explained by the photoisomerization of allylic chloride 4 to 5. When deuterated allylic chloride 4 was mixed with 2 mol% Ir(III) photocatalyst under blue LED light (Scheme 2B, entry 1), considerable isomerization from 4 to 5 was observed. However, this isomerization was depressed to 11% in the presence of Ni(0) complex (entry 2). To understand this observation, we examined the byproducts generated in the presence and absence of Ni(0) complex. When Ni(0) complex was omitted from the optimized reaction conditions (Scheme 2A), we observed considerable amounts of the allylic chloride dimerization byproduct. We believe this dimer is formed through the radical pair shown in Scheme 2B, which is prevalent in the absence of the Ni(0) complex. Although the presence of the Ni(0) complex suppresses photoisomerization, it does not completely shut down photoisomerization (Scheme 2B, entry 2). We surmise that the small amount of allylation product 7 formed in the optimized reaction with the Ni(0) complex (Scheme 2A) may be the result of small amounts of photoisomerization even in the presence of the Ni(0) complex. Therefore, the Ni(0)/L1 complex stabilizes the allylic chloride substrate to isomerization and decomposition during exposure to blue LED irradiation and Ir photoredox catalyst. Scheme 3. Proposed Mechanism
Cl Ni
NH Me 9 TFA
R
Me Me
8 Cl
H N TFA Ir(II)
Me Cl Me
NH R TFA 10
On the basis of these investigations, we propose the mechanism depicted in Scheme 3. The activated photocatalyst Ir(III)* oxidizes deprotonated amide 1a by single electron transfer to generate amidyl 8, which undergoes a 1,5-hydrogen atom transfer (1,5-HAT) to cleave a sp3 C‒H bond at the -position. The generated carbon radical 9 is trapped by allylic chloride 2a to provide 10, which yields -allylation product 3aa and chlorine radical through β-scission.14 The chlorine radical then oxidizes the Ir(II) photocatalyst to regenerate Ir(III) via another single electron transfer process to complete the catalytic cycle. During this process, the Ni(0) complex presumably stabilizes the allylic chloride substrate to isomerization and decomposition, which results in improved yield of the desired allylation product 3aa. In conclusion, by using photoredox catalysis and a [1,5]HAT process, we have developed a direct allylation of unactivated C(sp3)‒H bonds. This photocatalyzed transformation has a broad substrate scope of substituted amides and allylic chlorides. Various allyl-substituted amide products were obtained with good yields and high -selectivity.
ASSOCIATED CONTENT Supporting Information. The experimental procedures, mass, and NMR data. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author * Email:
[email protected] ORCID
Uttam K. Tambar: 0000-0001-5659-5355 Bin Xu: 0000-0003-3861-1141
ACKNOWLEDGMENT Financial support was provided by W. W. Caruth, Jr. Endowed Scholarship, Welch Foundation (I-1748), National Institutes of Health (R01GM102604), American Chemical Society Petroleum Research Fund (59177-ND1), Teva Pharmaceuticals Marc A. Goshko Memorial Grant (60011TEV), and Sloan Research Fellowship. We acknowledge Ludovic Troian-Gautier (UNC) and Tian Qin (UTSW) for fruitful discussions.
REFERENCES
[1,5]-HAT
Me
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HB
Cl Ir(III) h
Ir(III)*
-elimination Me
Me
NH R Me TFA 3aa
NH Me TFA 1a
H
B
(1) (a) Yus, M.; González-Gómez, J. C.; Foubelo, F. Catalytic Enantioselective Allylation of Carbonyl Compounds and Imines. Chem. Rev. 2011, 111, 7774‒7854. (b) Weaver, J. D.; Recio, III, A.; Grenning, A. J.; Tunge, J. A. Transition Metal-Catalyzed Decarboxylative Allylation and Benzylation Reactions. Chem. Rev. 2011, 111, 1846‒1913. (c) Yus, M.; González-Gómez, J. C.; Foubelo, F. Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products. Chem. Rev. 2013, 113, 5595‒5698. (d) Mishra, N. K.; Sharma, S.; Park, J.; Han, S.; Kim, I. S. Recent Advances in Catalytic C(sp2)−H Allylation Reactions. ACS Catal. 2017, 7, 2821‒2847. (2) (a) Sundararaju, B.; Achard, M.; Bruneau, C. Transition Metal Catalyzed Nucleophilic Allylic Substitution: Activation of Allylic Alcohols via -Allylic Species. Chem. Soc. Rev. 2012, 41,
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Page 5 of 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis 4467‒4483. (b) Butta, N. A.; Zhang, W. Transition Metalcatalyzed Allylic Substitution Reactions with Unactivated Allylic Substrates. Chem. Soc. Rev. 2015, 44, 7929‒7967. (3) (a) Uozumi, Y.; Danjo, H.; Hayashi, T. Cross-Coupling of Aryl Halides and Allyl Acetates with Arylboron Reagents in Water Using an Amphiphilic Resin-Supported Palladium Catalyst. J. Org. Chem. 1999, 64, 3384‒3388. (b) Denmark, S. E.; Werner, N. S. Cross-Coupling of Aromatic Bromides with Allylic Silanolate Salts. J. Am. Chem. Soc. 2008, 130, 16382‒16393. (c) Lee, K.; Kim, H.; Mo, J.; Lee, P. H. Palladium-Catalyzed Allyl Cross-Coupling Reactions with In Situ Generated Organoindium Reagents. Chem.Asian J. 2011, 6, 2147‒2157. (d) Yang, Y.; Buchwald, S. L. LigandControlled Palladium-Catalyzed Regiodivergent Suzuki−Miyaura Cross-Coupling of Allylboronates and Aryl Halides. J. Am. Chem. Soc. 2013, 135, 10642‒10645. (4) (a) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. C-H Activation for the Construction of C-B Bonds. Chem. Rev. 2010, 110, 890‒931. (b) Davies, H. M. L.; Bois, J. D.; Yu, J.-Q. C–H Functionalization in Organic Synthesis. Chem. Soc. Rev. 2011, 40, 1855‒1856. (c) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. C-H Bond Functionalization: Emerging Synthetic Tools for Natural Products and Pharmaceuticals. Angew. Chem., Int. Ed. 2012, 51, 8960−9009. (d) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q. Palladium-Catalyzed Transformations of Alkyl C−H Bonds. Chem. Rev. 2017, 117, 8754‒8786. (e) Chu, J. C. K.; Rovis, T. Complementary Strategies for Directed C(sp3)-H Functionalization: A Comparison of Transition-Metal-Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer. Angew. Chem., Int. Ed. 2018, 57, 62−101. (f) Wang, W.; Lorion, M. M.; Shah, J.; Kapdi, A. R.; Ackermann, L. Late-Stage Peptide Diversification by Position-Selective C-H Activation. Angew. Chem., Int. Ed. 2018, 57, 14700−14717. (5) (a) Han, S. B.; Gao, X.; Krische, M. J. Iridium-Catalyzed antiDiastereoand Enantioselective Carbonyl (Trimethylsilyl)allylation from the Alcohol or Aldehyde Oxidation Level. J. Am. Chem. Soc. 2010, 132, 9153‒9156. (b) Dechert-Schmitt, A.-M. R.; Schmitt, D. C.; Krische, M. J. Protecting-Group-Free Diastereoselective C-C Coupling of 1,3Glycols and Allyl Acetate through Site-Selective Primary Alcohol Dehydrogenation. Angew. Chem., Int. Ed. 2013, 52, 3195−3198. (c) Ohmatsu, K.; Ito, M.; Kunieda, T.; Ooi, T. Exploiting the Modularity of Ion-Paired Chiral Ligands for Palladium-Catalyzed Enantioselective Allylation of Benzofuran-2(3H)‑ones. J. Am. Chem. Soc. 2013, 135, 590‒593. (d) Chen, W.-Y.; Chen, M.; Hartwig, J. F. Diastereo- and Enantioselective Iridium-Catalyzed Allylation of Cyclic Ketone Enolates: Synergetic Effect of Ligands and Barium Enolates. J. Am. Chem. Soc. 2014, 136, 15825‒15828. (e) Næsborg, L.; Halskov, K. S.; Tur, F.; Mønsted, S. M. N.; Jørgensen, K. A. Asymmetric -Allylation of ,-Unsaturated Aldehydes by Combined Organocatalysis and Transition-Metal Catalysis. Angew. Chem., Int. Ed. 2015, 54, 10193‒10197. (f) Schwarz, K. J.; Amos, J. L.; Klein, J. C.; Do, D. T.; Snaddon, T. N. Uniting C1Ammonium Enolates and Transition Metal Electrophiles via Cooperative Catalysis: The Direct Asymmetric α‑Allylation of Aryl Acetic Acid Esters. J. Am. Chem. Soc. 2016, 138, 5214‒5217. (g) Huo, X.-H.; He, R.; Zhang, X.; Zhang, W.-B. An Ir/Zn Dual Catalysis for Enantio- and Diastereodivergent ‑Allylation of ‑Hydroxyketones. J. Am. Chem. Soc. 2016, 138, 11093‒11096. (h) Shu, W.; Genoux, A.; Li, Z.-D.; Nevado, C. -Functionalizations of Amines through Visible-Light-Mediated, Redox-Neutral C-C Bond Cleavage. Angew. Chem., Int. Ed. 2017, 56, 10521‒10524. (f) Kim, S. W.; Zhang, W.-D.; Krische, M. Catalytic Enantioselective Carbonyl Allylation and Propargylation via Alcohol-Mediated Hydrogen Transfer: Merging the Chemistry of Grignard and Sabatier. Acc. Chem. Res. 2017, 50, 2371‒2380.
(6) (a) Robertson, J.; Pillaia, J.; Lush, R. K. Radical Translocation Reactions in Synthesis. Chem. Soc. Rev. 2001, 30, 94‒103. (b) Chiba, S.; Chen, H. sp3 C–H Oxidation by Remote H-Radical Shift with Oxygen- and Nitrogen-Radicals: A Recent Update. Org. Biomol. Chem. 2014, 12, 4051‒4060. (c) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. Radicals: Reactive Intermediates with Translational Potentia. J. Am. Chem. Soc. 2016, 138, 12692‒12714. (d) Stateman, L. M.; Nakafuku, K. M.; Nagib, D. A. Remote C–H Functionalization via Selective Hydrogen Atom Transfer. Synthesis 2018, 50, 1569−1586. (7) (a) Choi, G. J.; Zhu, Q.; Miller, D. C.; Gu, C. J.; Knowles, R. R. Catalytic Alkylation of Remote C–H Bonds Enabled by ProtonCoupled Electron Transfer. Nature 2016, 539, 268‒271. (b) Chu, J. C. K.; Rovis, T. Amide-directed Photoredox-catalysed C–C Bond Formation at Unactivated sp3 C–H Bonds. Nature 2016, 539, 272‒275. (c) Chen, D.-F.; Chu, J. C. K.; Rovis, T. Directed γ‑C(sp3)−H Alkylation of Carboxylic Acid Derivatives through Visible Light Photoredox Catalysis. J. Am. Chem. Soc. 2017, 139, 14897‒14900. (d) Shu, W.; Nevado, C. Visible-Light-Mediated Remote Aliphatic C-H Functionalizations through a 1,5Hydrogen Transfer Cascade. Angew. Chem., Int. Ed. 2017, 56, 1881‒1884. (e) Dauncey, E. M.; Morcillo, S. P.; Douglas, J. J.; Sheikh, N. S.; Leonori, D. Photoinduced Remote Functionalisations by Iminyl Radical Promoted C–C and C–H Bond Cleavage Cascades. Angew. Chem., Int. Ed. 2018, 57, 744‒748. (f) Yuan, W.; Zhou, Z.-J.; Gong, L.; Meggers, E. Asymmetric Alkylation of Remote C(sp3)–H Bonds by Combining Proton-coupled Electron Transfer with Chiral Lewis Acid Catalysis. Chem. Commun. 2017, 53, 8964‒8967. (8) (a) Zhang, J.; Li, Y.; Zhang, F.-Y.; Hu, C.-C.; Chen, Y.-Y. Generation of Alkoxyl Radicals by Photoredox Catalysis Enable Selective C(sp3)–H Functionalization under Mild Reaction Conditions. Angew. Chem., Int. Ed. 2016, 55, 1872‒1875. (b) Wang, C.-Y.; Harms, K.; Meggers, E. Catalytic Asymmetric Csp3–H Functionalization under Photoredox Conditions by Radical Translocation and Stereocontrolled Alkene Addition. Angew. Chem., Int. Ed. 2016, 55, 13495‒13498. (c) Hu, A.-H.; Guo, J.-J.; Pan, H.; Tang, H.-M.; Gao, Z.-B.; Zuo, Z.-W. -Selective Functionalization of Alkanols Enabled by Visible-Light-Induced Ligand-to-Metal Charge Transfer. J. Am. Chem. Soc. 2018, 140, 1612‒1616. (d) Wu, X.-X.; Zhang, H.; Tang, N.-N.; Wu, Z.; Wang, D.-P.; Ji, M.-S.; Xu, Y.; Wang, M.; Zhu, C. Metal-free Alcoholdirected Regioselective Heteroarylation of Remote Unactivated C(sp3)–H Bonds. Nat. Commun. 2018, 9, 3343‒3350. (e) Li, G.-X.; Hu, X.-F.; He, G.; Chen, G. Photoredox-mediated Remote C(sp3)– H Heteroarylation of Free Alcohols. Chem. Sci. 2019, 10, 688–693. (9) Wu, K.; Wang, L.; Colón-Rodríguez, S.; Flechsig, G.-U.; Wang, T. Amidyl Radical Directed Remote Allylation of Unactivated sp3 C−H Bonds by Organic Photoredox Catalysis. Angew. Chem., Int. Ed. 2019, 58, 1774−1778. (10) See supporting information for optimization details. (11) (a) Tucker, J. W.; Stephenson, C. R. J. Shining Light on Photoredox Catalysis: Theory and Synthetic Applications. J. Org. Chem. 2012, 77, 1617‒1622. (b) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.; MacMillan, D. W. C. The Merger of Transition Metal and Photocatalysis. Nat. Rev. Chem. 2017, 1, 0052. (12) In addition to the TFA-protected amides, benzoyl-protected and benzenesulfonyl-protected amides were also tested, but
