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Letter
Visible-Light-Mediated Reactions of Electrophilic Radicals with Vinyl and Allyl Trifluoroborates. Daniel Fernandez Reina, Alessandro Ruffoni, Yasair S.S. AlFaiyz, James J. Douglas, Nadeem S. Sheikh, and Daniele Leonori ACS Catal., Just Accepted Manuscript • Publication Date (Web): 15 May 2017 Downloaded from http://pubs.acs.org on May 15, 2017
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ACS Catalysis
Visible-Light-Mediated Reactions of Electrophilic Radicals with Vinyl and Allyl Trifluoroborates Daniel Fernandez Reina,a‡ Alessandro Ruffoni,a‡ Yasair S. S. Al-Faiyz,b James J. Douglas,c Nadeem S. Sheikh,b* and Daniele Leonoria* a
b
School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK. Department of Chemisc try, Faculty of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia. AstraZeneca, Silk Road Business Park, Macclesfield SK10 2NA, UK.
ABSTRACT: Visible-light photoredox catalysis enables the vinylation and allylation of electrophilic radicals with readily available potassium trifluoroborate reagents. The processes show good functional group compatibility and mechanistic and computational studies have elucidated some of the aspects associated with the key radical addition step. Photoredox, vinylation, allylation, trifluoroborate, electrochemistry.
The addition of carbon-centered radicals to olefins is one of the most used reactions for the construction of C– C bonds.1-2 Despite its apparent simplicity, this process is mechanistically intriguing as it relies on a complex interplay between enthalpic, steric and polar effects.3-5 State correlation diagrams that describe these transformations involve three components: the reactants in (i) the ground, (ii) the excited state and (iii) the polar charge transfer configuration (CTC).5-6 As a result, the identification of polarity-matched systems might result in more facile reactions owing to the stabilization of the CTC in the transition state.7 A classical example is the addition of electrophilic radicals (e.g. malonyl radical) to electron rich olefins like enol ethers and enamines (Scheme 1A).8-9 A) Addition of electrophilic radicals to enol ethers: known OR1
OR1 R
δ+
R
B) This work: radical addition to vinyl-BF3K: unexplored BF 3K R a
a
R
δ+
a b
BF 3K
BF 3K
b R
b
Key questions: polarity match? a vs b selectivity? compatible under photoredox conditions?
SCHEME 1. Polarised radical addition to olefins: (A) enol ethers and (B) vinyl-BF3K. Vinyl potassium trifluoroborates (vinyl-BF3K) are extensively used in contemporary organic synthesis owing to (i) their versatility in transition metal-catalyzed reactions, (ii) their chemical stability, (iii) ease of preparation and (iv) their availability from commercial suppliers.10 Surprisingly however, their use as olefinic partners in radical addition reactions has been comparatively overlooked,
with, to the best of our knowledge, only two examples reported in the literature by Koike and Akita11-12 and, very recently, by Studer13 and Aggarwal.14 In this paper we describe our work on understanding and exploiting the reactivity of vinyl- and allyl-BF3K reagents with electrophilic radicals under photoredox catalysis (Scheme 1B).15-19 This has resulted in the development of novel transition metalfree vinylation and allylation processes. At the outset, we were concerned about the possibility of employing vinyl-BF3K reagents in photoredox processes owing to the potential SET oxidation of the C–B bond as pioneered by Molander in the chemistry of benzylic-BF3K reagents.20-21 However, cyclic voltammetry analysis on several vinyl-BF3K revealed high potentials for oxidation (E1/2ox > 2.0 V vs SCE)22 which could make them suitable coupling partners in visible-light-mediated transformations. A selection of vinyl/allyl-BF3– 22reagents (A–E) were then studied by DFT and characterized in terms of electron donor properties by calculating their adiabatic ionization potential (IP) and absolute electronegativity (χDB) (Scheme 2A).22 When compared to known IP and χDB for other electron rich olefins (e.g. methyl vinyl ether, F),23 A–E displayed remarkably lower values, which indicate a highly electron rich character. We then decided to assess their preferred site of radical attack by determining the carbon spin density in the triplet state (ππ*) as well as the enthalpy of reaction (–∆Hr) with the electrophilic malonyl radical24-25 (electrophilicity index ω–rc = 1.15 eV)22 (Scheme 2B).9, 26 This study revealed a potential difference in the site-reactivity profile of vinyl-BF3K reagents with respect to other electron rich olefins like enol ethers. According to our calculations reagents A–D should preferen-
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tially react at the ipso-C (Ca) owing to the higher spin density and the more favorable reaction enthalpy.
A) Olefin electron donor properties [UB3LYP/6-31+G(d)] BF 3 Me B
A IP (eV) χDB (eV)
BF 3
4.15 –0.14
BF 3 Ph
4.53 0.22
Me
BF 3
Me D
C 4.27 0.49
OMe
BF 3
4.24 0.16
E
F
5.14 0.56
8.69 3.6
B) Spin density and enthalpies of reaction with malonyl radical [UB3LYP/6-31+G(d)] EtO 2C
a
EtO 2C δ+
EtO 2C
EtO 2C BF 3
BF 3 b a A
Me b a B
BF 3 Ph b a C
EtO 2C
b
a b
EtO 2C
Me
BF 3
Me b a D
BF 3 b a E
OMe b a F
Mulliken atomic spin density (ππ* triplet state) a b
1.00 0.99
0.98 0.90
0.83 0.32 –∆H r (KJ
a b
89.5 85.6
86.1 72.2
113.6 44.8
0.99 0.86
0.86 1.01
0.821 1.01
mol –1) 80.3 59.7
47.8 78.3
18.7 57.3
SCHEME 2. Computational studies on the electron donor properties of vinyl-BF3 reagents and their reaction with malonyl radical. To assess this hypothesis, we started by investigating the reaction of vinyl-BF3K reagent 1a and malonates 2a–c. As illustrated in Scheme 3, we were pleased to find that with bromomalonate 2a (E1/2red = –0.62 V vs SCE)27 using eosin Y (EY) as the photoredox catalyst, EtN(i-Pr)2 as the base
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in MeOH under green LEDs irradiation (530 nm), the ipso-vinylated product 3a was obtained in 81% yield (entry 1). Such a reactivity is intriguing, because its exploitation would represent an umpolung strategy for a formal radical alternative to sp3–sp2 Suzuki-type processes. Control experiments (entries 2–4) and light ON-OFF reaction analysis22 confirmed the requirement for light, photocatalyst and base. We then evaluated the possibility of using (i-Pr)2NEt in sub-stoichiometric amounts but this resulted in a lower yield (entry 5). Other bases, solvents and photoredox catalysts were evaluated but they generally provided 3a with lower efficiency.28 Iodo-malonate 2b (E1/2red = –0.74 V vs SCE) was also a competent coupling partner (entry 7) while chloro-malonate 2c (E1/2red = –0.52 V vs SCE) gave 3a in very low yield (entry 8). This was surprising as its redox profile is well in the range for SET reduction from the excited state of EY (*EY). We attributed this lack of reactivity to the fact that 2c does not serve as competent quencher of *EY as determined by SternVolmer studies (see below). BF 3K Me
+
CO 2Et EY (1 mol%), base
EtO 2C X
Me 1a (1.0 equiv.)
2a–c (1.0 equiv.)
EtO 2C
MeOH (0.1 M), rt visible light
CO 2Et Me 3a
Me
Entry
X
Base (equiv.)
Light Source
Yield (%)
1 2 3 4 5 6 7 8
Br Br Br Br Br Br I Cl
EtN(i-Pr) 2 (1.0) – EtN(i-Pr)2 (1.0) EtN(i-Pr)2 (1.0) EtN(i-Pr)2 (0.2) K 2CO3 (1.0) EtN(i-Pr)2 (1.0) EtN(i-Pr)2 (1.0)
green LEDs green LEDs green LEDs – green LEDs green LEDs green LEDs green LEDs
81 traces – – 24 37 67 6
SCHEME 3. Optimization of the visible-lightmediated vinylation of malonates 2a–c.
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R
BF 3K R4 2
Photoredox Vinylations
EtO 2C
R3 1a–h
Me Me 3a 81%
Ar
R2
MeOH (0.1 M), rt green LEDs
2a,d–o
3l 3m 3n 3o
: : : :
EWG EWG EWG EWG
Me 3b 41% E:Z = 1.5:1
= CO 2Et = CN = CN = SO 2Ph
; ; ; ;
Me 3c 74% [1 gram]
Ar = Ph : Ar = PMP : Ar = p-FPh : Ar = Ph :
Br
NC 3d 3e 40% 67% E:Z = 1.5:1 E:Z = 1.5:1
31% 47% 42% 21%
R R1 R4
R3 3a–t
O
EWG
4 NO 2
CO 2Et
Me Me
p-FPh 3h 90%
Ph 3j 36%
NO 2
NO 2
5b 45%
NO 2
CO2Et
CN
F
F
F
Ph
Me EY (2 mol%) i-Pr 2NEt (2.0 equiv.)
3r 75%
3s 47%
3t 16%
R R1
EWG
MeOH (0.1 M), rt green LEDs
Ph(O)C
5d 67%
5c 47%
Ph
F
5a–i O
EtO 2C
Me O
F
3q 57%
2–c,g–i,m
N
3k 90%
Ph
Ar
R R1 Br
N
O
Me 3i 35%
C(O)Ph
Ph(O)C
Ts
EtO 2C
Me
CO 2Et
5e 62%
5f 68%
5g 53%
N
N
O
CN
5a 57%
Me
Me
Me NO 2
CO 2Et
EtO 2C
NO 2
+
NO 2
PMP 3g 71%
Me 3p 72%
Photoredox Allylations
NO 2
Ph 3f 70%
CN
O2N
BF 3K
Ar
EWG
Me
Me
R4 R3
EWG
EY (2 mol%) i-Pr 2NEt (2.0 equiv.)
R R1 Br
EtO 2C
CO 2Et
R2
EWG
+
Ph
O
Me O
F 3C
5h 65%
5i 60%
Modification of bioactive molecules O
N N
N N O
Ph
Ph
Ph
Ph
O
O
O R
Me phenylbutazone (6) [veterinary NSAID]
O
O
O
Me Me
Me Ph
MeO
Me 8a 66%
8b 74%
8c 70%
t-Bu
MeO
R
t-Bu
avobenzone (7) [sunscreen]
Me 9a 57%
9b 42%
SCHEME 4. Scope of the visible-light-mediated vinylation and allylation of electrophilic radicals. With these optimized conditions in hand, we evaluated the scope of this photoredox vinylation reaction (Scheme 4). Pleasingly, our protocol enabled the reaction of various vinyl-BF3K partners as shown by the formation of products containing di-, tri- and tetra-substituted olefins (3a–c) and could be run on a gram-scale. Several functional groups were tolerated such as a terminal alkyl bromide (3d) and a nitrile (3e). Styrenyl-BF3K reagents were also successful with both electron donating and electron withdrawing substituents (3f–h). We then looked at the alkyl bromide unit and extended the scope to methyl-Brmalonate and a barbituric acid derivative which gave access to products with fully substituted C-centres (3i–k). We then evaluated the use of radical precursors with a single electron-withdrawing group. In this case 4-MeOpyridine29 was used as an additive (40 mol%) to facilitate the SET reduction en route to the carbon-radical.22 As these radicals are not as electrophilic as those previously employed,8 they provided the desired products 3l–o in somewhat diminished yields. Finally, we extended this methodology to electron poor benzyl bromides that provided 3p–t in good to moderate yields. The successful formation of 3p–t offers a transition metal-free alternative to current methods for the vinylation of benzylic bromides that normally requires Pd- or Cu-based catalysts.3031
Having developed a photoredox transition metal-free vinylation of electrophilic radicals, we decided to evaluate if allyl-BF3K (4) could serve as competent radical allylating
agent. Our DFT studies supported its ability to serve as highly electron rich system (Scheme 2) and we were please to see that both benzyl and malonyl-type bromides could be engaged under identical reaction conditions to provide the corresponding allylated products (5a–i). As many biologically active compounds contain 1,3dicarbonyl motifs, we showcased the applicability of this methodology with the late-stage vinylation and allylation of the veterinary anti-inflammatory drug phenylbutazone (6) and the sunscreen agent avobenzone (7), which, after bromination,22 gave 8a–c and 9a–b in good yields. Having evaluated the scope of these photoredox transformations we decided to perform mechanistic and computational studies to gain more information about the reaction mechanism. As illustrated in Scheme 5A, fluorescence quenching studies were conducted on all reaction partners and the quencher rate coefficients were obtained using the Stern-Volmer relationship. We also determined all the redox potentials by cyclic voltammetry analysis. A salient conclusion of this study is that all the carbonradical precursors (with the exception of Cl-malonate) quench *EY at a significantly higher rate than (i-Pr)2NEt. As a result, we propose that upon visible-light irradiation, *EY preferentially undergoes oxidative quench with the alkyl bromides I providing access to the corresponding carbon-radicals II by SET reduction and fragmentation (Scheme 5B).32-33 Radical ipso-addition to the vinyl-BF3K reagent III, where the highest spin density is located,
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ought to be highly electron rich in nature, it can directly close the photoredox cycle or regenerate the malonyl radical II by oxidative SET with I. However, when the reaction was run in the absence of EtN(i-Pr)2 but with Na2CO3 as the base, the reaction product was obtained in a considerably lower yield (see Scheme 3, entry 6).
would deliver a β-boron radical IV. As the BF3 group cannot be expelled as a borato radical (endothermic process),34 we propose that a SET oxidation is necessary to trigger the olefination and give V. At the moment we cannot exclude that other productive pathways might be operative from the β-boryl radical IV. As this species is A) Stern-Volmer quenching rates [kq (M –1 s–1)] and redox potentials (V vs SCE) KF 3B
Me
Et N
Me E1/2 ox = 2.29 2.9 10 4
EtO 2C
i-Pr i-Pr E1/2 ox = 0.50 5.3 10 5
Br E1/2 red = –1.08 1.8 10 6
10 5
10 4
EtO 2C
CO 2Et
I E1/2 red = –0.74 2.9 10 6 10 7
10 6
kq (M –1 s–1) EtO 2C
CO 2Et O 2N
10 6
1.2 E1/2 red = –0.52
EtO 2C
– BF 3
R2 V
NR 3
EWG
δ+
IV
SET R R1 Br I
EWG
R R1 II
EWG
δ+
BF 3K
R
a b
R1 R2
KF 3B
EWG
EtO 2C
R
EY •+
*EY
N
2.3 10 6
1.4 E1/2 red = –0.61
3.0 10 6
E1/2 red = –0.62
E1/2 red =–0.06 OMe
– e–
EY SET
MeO 2C
C) Enthalpic vs polar effects [UB3LYP/6-31G(d)]
R R1
EWG
NR 3
CO 2Et Br
10 5
B) Proposed mechanism
EtO 2C
Br
Cl
mol –1)
–∆Hr (KJ d(C–C) (Å) δ TS
BF 3 R
Me b a B
BF 3 Ph b a C
Me
BF 3
Me b a D
BF 3 b a E
a
b
a
b
a
b
a
b
86.1 2.28 –0.08
72.2 2.14 –0.09
113.6 2.45 –0.06
44.8 2.07 –0.08
80.3 2.29 –0.08
59.7 2.20 –0.13
78.3 2.22 –0.07
47.8 2.13 –0.12
R2
R1 III
SCHEME 5. A) Luminescence quenching studies and cyclic voltammetry studies. B) Proposed mechanism for photoredox vinylations. C) DFT studies on enthalpic and polar effects.
As the radical ipso-addition is a key aspect of this reaction pathway, we performed further DFT studies aimed at evaluating enthalpic and polar contributions in the transition state. As illustrated in Scheme 5C, we calculated the reaction enthalpy (–∆Hr) as well as the bond formation distance [d(C–C)] and the δTS of the charge transfer complex8, 35 from the vinyl/allyl-BF3 reagents (B–E) to the malonyl radical for both reactions at Ca and Cb. According to our studies, radical ipso-additions (Ca), while energetically more favourable, have low |δTS| values and therefore are less influenced by polar effects compared to the additions at Cb. We also observed a good correlation between –∆Hr and d(C–C)22 which is in agreement with the Hammond postulate: the reaction exothermicity is directly related to the earliness of the corresponding transition state. Hence, our results suggest that even if highly electron rich, the behavior of vinyl/allyl-BF3K in the reaction with electrophilic radicals is predominantly controlled by enthalpic effects. In conclusion, we have developed an easy and simple method to perform transition metal-free vinylation and allylation reactions of electrophilic C-radicals using readi-
ly available potassium trifluoroborate reagents. We are currently evaluating the possibility to render these transformations asymmetric.
ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Details of all synthetic, electrochemical, spectroscopic and computational experiments (PDF).
AUTHOR INFORMATION Corresponding Author * Email:
[email protected]. ORCID: 0000-0002-7692-4504 Website: http://leonoriresearchgroup.weebly.com. * Email:
[email protected] Author Contributions D. L. designed the project and wrote the manuscript with the contribution of all the authors. D. F. R. and A.R. performed the experimental work. N. S. S. and D. L. envisaged the com-
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putational investigation and Y. S. S. A-F. assisted with this. All authors analyzed the results. ‡These authors contributed equally.
ACKNOWLEDGMENT D. L. thanks the European Union for a Career Integration Grant (PCIG13-GA-2013-631556), EPSRC for a research grant (4500284613). D. F. R. thanks AstraZeneca for a PhD CASE Award. A. R. thanks the Marie Curie Actions for a Fellowship (703238). Y. S. S. A-F. and N. S. S. gratefully acknowledge the support offered by the Department of Chemistry, King Faisal University, Saudi Arabia.
REFERENCES (1) Walling, C.; Huyser, E. S. Free Radical Additions to Olefins to Form Carbon-Carbon Bonds 2011, Organic Reactions. 13:3:91. (2) Zard, S. Z. Radical Reactions in Organic Synthesis 2003, Oxford Chemistry Masters. (3) Wu, J. Q.; Beranek, I.; Fischer, H. Helv. Chim. Acta 1995, 78, 194-214. (4) Tedder, J. M. Angew. Chem. Int. Ed. 1982, 21, 401-410. (5) Fischer, H.; Random, L. Angew. Chem. Int. Ed. 2001, 40, 1340-1371. (6) Shaik, S. S.; Shurki, A. Angew. Chem. Int. Ed. 1999, 38, 586-625. (7) Giese, B.; He, J.; Mehl, W. Chem. Ber. 1988, 121, 20632066. (8) Weber, M.; Fischer, H. Helv. Chim. Acta 1998, 81, 770780. (9) Lalevee, J.; Allonas, X.; Genet, S.; Fouassier, J.-P. J. Am. Chem. Soc. 2003, 125, 9377-9380. (10) Molander, G. A. J. Org. Chem. 2015, 80, 7837-7848. (11) Koike, T.; Akita, M. Acc. Chem. Res. 2016, 49, 19371945. (12) Yasu, Y.; Koike, T.; Akita, M. Chem. Commun. 2013, 49, 2037-2039. (13) Kisschewitz, M.; Okamoto, K.; Much-Lichtenfeld, C.; Studer, A. Science 2017, 355, 936-938. (14) Silvi, M.; Sanford, S.; Aggarwal, V. K., J. Am. Chem. Soc. 2017, 139, 5736-5739. (15) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075-10166. (16) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem. Rev. 2016, 116, 10035-10074. (17) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322-5363. (18) Narayannam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2008, 40, 102-113. (19) Xuan, J.; Zhang, Z.-G.; Xiao, W.-J. Angew. Chem. Int. Ed. 2015, 54, 15632-15641. (20) Tellis, J. C.; Kelly, C. B.; Primer, D. N.; Jouffroy, M.; Patel, N. R.; Molander, G. A. Acc. Chem. Res. 2016, 49, 1429-1439. (21) Tellis, J. C.; Primer, D. N.; Molander, G. A. Science 2014, 345, 433-436. (22) See SI for more informations. (23) Lalevee, J.; Allonas, X.; Fouassier, J.-P. J. Org. Chem. 2004, 70, 814-819.
(24) Baciocchi, E.; Giese, B.; Farshchi, H.; Ruzziconi, R. J. Org. Chem. 1990, 55, 5688-5691. (25) Santi, R.; Bergamini, F.; Citterio, A.; Sebastiano, R.; Nicolini, M. J. Org. Chem. 1992, 57, 4250-4255. (26) Shaik, S. S.; Canadell, E. J. Am. Chem. Soc. 1990, 112, 1446-1452. (27) Roth, H. G.; Romero, N. A.; Nicewicz, D. A. Synlett 2016, 27, 714-723. (28) See SI for the full optimization table. In the case of low yielding reaction the major product was diethyl malonate which can be formed upon radical H-atom abstraction. (29) Liu, Q.; Yi, H.; Liu, J.; Yang, Y.; Zhang, X.; Zeng, Z.; Lei, A. Chem. Eur. J. 2013, 19, 5120-5126. (30) Crawforth, C. M.; Burling, S.; Fairlamb, J. J. S.; Kapdi, A. R.; Taylor, R. J. K.; Whitwood, A. C. Tetrahedron 2005, 61, 9736-9751. (31) Zhang, X.; Yi, H.; Liao, Z.; Zhang, G.; Fan, C.; Quin, C.; Liu, J.; Lei, A. Org. Biomol. Chem. 2014, 12, 6790-6793. (32) Williams, T. M.; Stephenson, C. R. J. Synlett 2016, 27, 754-758. (33) Furst, L.; Matsuura, B. S.; Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C. R. J. Org. Lett. 2010, 12, 31043107. (34) Walton, J. C.; McCarroll, A. J.; Chen, Q.; Carboni, B.; Nziengui, R. J. Am. Chem. Soc. 2000, 122, 5455-5463. (35) Wong, M. W.; Pross, A.; Radom, L. J. Am. Chem. Soc. 1994, 116, 6284-6292.
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EWG
R R1 Br
+ R
BF 3K R4 2
EWG
eosin Y
R2
visible light
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R R1 R4
R3
R3
sp3-sp 2 radical coupling also applied to allyl-BF3 34 examples modification of biomolecules DFT studies
via polarised radical addition OR R
OR
δ+ R
BF 3K vs
R
δ+
known reactivity
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BF 3K R
this work
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