Subscriber access provided by RYERSON UNIV

Communication
An Efficient and Stereoselective Nitration of Mono-
and Di-Substituted Olefins with AgNO2 and TEMPO
Soham Maity, Srimanta Manna, Sujoy Rana, Togati Naveen, Arijit Mallick, and Debabrata Maiti
J. Am. Chem. Soc., Just Accepted Manuscript DOI: 10.1021/ja311942e Publication Date (Web): 13 Feb 2013
Downloaded from http://pubs.acs.org on February 17, 2013

Just Accepted

Just Accepted manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides Just Accepted as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. Just Accepted manuscripts
appear in full in PDF format accompanied by an HTML abstract. Just Accepted manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI). Just Accepted is an optional service offered
to authors. Therefore, the Just Accepted Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the Just
Accepted Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these Just Accepted manuscripts.

Journal of the American Chemical Society 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.
Page 1 of 5 Journal of the American Chemical Society

1
2 An Efficient and Stereoselective Nitration of Mono- and Di-Substituted Olefins with
3
AgNO2 and TEMPO
4
5 Soham Maity,a Srimanta Manna,a Sujoy Rana,a Togati Naveen,a Arijit Mallick,b and Debabrata Maitia*
6 a
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
7 b
8 Physical/Materials Chemistry Division, National Chemical Laboratory, Dr. Homi Bhaba Road, Pune 411008, India
9 RECEIVED DATE (automatically inserted by publisher); Email: dmaiti@chem.iitb.ac.in
10
11
12 olefins on the basis of electronic and steric environment of
Abstract: Nitroolefin is a common and versatile reagent,
13 the olefin.
synthesis of which from olefin is generally limited by the
14 formation of mixture of cis and trans compounds. Here Scheme 2. Synthesis of nitroolefin by AgNO2/TEMPO
15 we report that silver nitrite (AgNO2) along with TEMPO can
TEMPO
16 promote the regio and stereoselective nitration of a broad R2 R2
AgNO2/TEMPO
17 range of olefins. This work discloses a new and efficient R1 R1
NO2 Me Me
DCE, 70 C Me N Me
approach wherein starting from olefin, nitroalkane radical R3
18
19 formation and subsequent transformations lead to the
R3
.
O

20 desired nitroolefin in a stereoselective manner.

Use of TEMPO in combination with AgNO2 gave 99% yield
21 Nitroolefins are building blocks for generating of (E)--nitro styrene in dichloroethane.12 Under the
22 molecules of biological and pharmaceutical relevance.1 optimized condition, a gram scale reaction resulted in 88%
23 These are widely used in different carbon-carbon bond isolated yield of the desired nitro product (Scheme 3).
24 forming reactions like Michael reaction,2 cycloaddition,3
Scheme 3. Gram scale reaction with styrene
25 Morita-Baylis-Hillman reaction,4 and for the generation of
26 oximes,5 hydroxylamines, nitroalkanes,6 aliphatic amines AgNO2 /TEMPO
NO2

27 and nitroso compounds.3a, b Nitroolefins are conventionally DCE, 70 C

28 synthesized by Henry reaction7 which relies upon base 1g [gram-scale reaction] isolated yield: 88%
29 mediated condensation of an aldehyde or ketone with a
nitroalkane. However, synthesis of nitroolefin via Scheme 4. Stereoselective synthesis of nitrostyrenesa
30
incorporation of a nitro group directly into the olefin is a
31
powerful and preferred class of reactions.8 In this context,
32 development of an efficient and practical method of regio
33 and stereoselective nitration of olefin is highly desirable.9
34
35 Despite significant developments, nitroolefin synthesis
36 is eluded by severe limitations.8 Most importantly, an
37 undesirable mixture of E/Z isomers was obtained.8a, 8b In
addition, prior methods either employ harsh or complex
38
reaction condition8c, 8d and/or suffer from poor substrate
39
scope.8e, 8f Further, olefins attached with heterocycles and
40 in complex settings have not been explored.8 One of the
41 approaches to solve these problems lies in discovering a
42 nitration protocol that is highly reactive, yet selective
43 enough for a broad range of olefins.
44
45 Scheme 1. Proposed pathway for nitroolefin synthesis
46
47 R1
R2
AgNO2
R1
.
R2
NO2 TEMPO/ AgNO2
R2
NO2
R1
48 R3
R3 H R3
49
Recently, we reported an ipso-nitration reaction in which
50
nitro radical is generated from bench stable nitrate salt.10
51 Following this concept, it was envisioned that if an olefin is a
Isolated yield of the E isomer. Reaction mixtures were analyzed by
52 reacted under these conditions, nitro radical would generate GC-MS and/or 1H-NMR to determine E/Z ratio. olefin (0.5 mmol, 1
53 a carbon centered radical which can be further oxidized to equiv.), AgNO2 (3 equiv.), TEMPO (0.4 equiv.), molecular sieves 4
54 give the corresponding nitroolefin (Scheme 1). Herein an (MS, 150 mg), 70 C, DCE (2 mL), 12 h; bolefin (0.25 mmol),
55 efficient and user-friendly reaction conditions have been 4.8 equiv AgNO2 and 0.6 equiv TEMPO; cyield of E only;
d
isolated as E/Z mixture; eolefin (0.25 mmol), 3 equiv AgNO2 and
56 discovered using silver nitrite (AgNO2) in combination with
0.4 equiv TEMPO, MS (80 mg), DCE (1 mL).
57 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)11 to effect
58 highly selective nitration of olefins (Scheme 2). Site of Previously, 1-methoxy-4-(2-nitrovinyl)benzene8e was
59 nitration can be predicted in complex settings with multiple obtained as a mixture of E/Z isomers in a ~1:1-ratio from 4-
60 methoxy styrene and nitric oxide (NO). Using an alternate

ACS Paragon Plus Environment

 Journal of the American Chemical Society Page 2 of 5

1
2
3 approach with AgNO3/CH3COCl, nitrostyrene was demand; therefore -methyl styrene produced the desired
4 synthesized in 1:1 E/Z mixture.8h Notably, only (E)-product product (4n) in slightly lower yield. 1,2-divinylbenzene was
5 was obtained under present AgNO2/TEMPO protocol selectively mono-nitrated in 70% yield (4r).
6 (Schemes 3 and 4). Encouraged by these results, nitration of Having demonstrated the protocol on styrene
7 electronically and sterically demanding styrene derivatives derivatives, aliphatic olefins of different complexity were
8 was investigated. Different halogen substituted styrenes investigated. A non-activated monosubstituted olefin was
9 were nitrated with equal ease (4e, 4f and 4k, 92-97% yield). nitrated in an excellent yield (5a, 95%). Nitration of
10 A number of functional moieties were tolerated under these terminal olefins with either ester (5c) or halide (5d) on a
11 reaction conditions, such as alkyl (4b), naphthyl (4l), distal position proceeded smoothly. Homoallyl benzene
12 methoxy (4a and 4j), carbonyl (4h), nitro (4g and 4p), ester also gave the desired nitro product (5j). In cases where
13 (4d), amide (4i), as well as cyano (4c). It was evident that monosubstituted olefins were absent, nitration occurred at
electronic and steric effect of the substituents had little/no the di-substituted olefins (5g-5i). Natural product, such as
14
effect on the yield of the desired product. Specifically, all (+)-limonene (5e) was nitrated in acceptable yield with high
15
these reactions exclusively formed (E)-nitro product in regio- and stereoselectivity. An internal olefin (E)-4-octene
16 preparatively useful yield. Given the broad utility of produced thermodynamically stable (E)-4-nitrooctene (5h)
17 nitrostyrenes in bulk/fine chemical and pharmaceutical via rotation of the C4C5 bond upon formation of the
18 industries, the direct stereoselective nitration of styrene TEMPO-adduct (vide infra).
19 derivatives is of great importance.13 Next, we sought to investigate whether the site selectivity of
20 olefin nitration is sensitive to the steric and electronic
Scheme 5. Scope of nitration with aliphatic olefina
21 environment. When a competition experiment with 1-
22 R2
decene and (E)-4-octene was carried out, nitration of the
R2
23 AgNO2/TEMPO
NO2 former olefin was observed exclusively.12 Consistent with
R1 R1
24 DCE, 70 C E only this observation, terminal olefin was selectively nitrated in
R3 R3
25 the presence of cyclic internal olefin in case of (+)-limonene
26 Me NO2
NO2 (5e). From these observations and competition experiments,
27 5a, 95% 5b, 86% we were able to outline the order of reactivity of olefins as
28 O follows:
O2N R2 R2
29 O2N OMe Br
> >>
5c, 80% 5d, 75%c R1 R1 R1
30 (E:Z= 6:1)b,c R3
31 Me
mono-substituted di-substituted tri-substituted
32 O2N
Me
Me
33 NO2 Olefin such as cis-2-hexene is without any electronic
34
Me
Me bias and therefore two regioisomeric nitroolefin products
35 Me Me were obtained in 3:1 ratio (5i, 78%). In cases with unequal
NO2
NO2 electronic environment at two olefinic carbon centers, such
36 5e, 69% 5f, 35% 5g, 76%e 5h, 51%f
(E:Z= 3:1)d
as in 5l, nitration occurred at the site far from the electron-
37 Me
withdrawing group.
38 NO2
NO2
39 CH3 Scheme 6. Scope of heterocyclic olefina
CH3
40 O2N
5i, 78% 5j, 53% 5k, 30%
41 (C2:C3= 3:1)e,g (E:Z= 40:1)d
42
O
43
44 O2N O NO2
45
5l, 55%e 5m, 10%
46 a
Isolated yield of the E isomer. Reaction mixtures were analyzed by
47 GC-MS and/or 1H-NMR to determine E/Z ratio. olefin (0.5 mmol, 1
48 equiv.), AgNO2 (3 equiv.), TEMPO (0.4 equiv.), molecular sieves 4
49 (MS, 150 mg), 70 C, DCE (2 mL), 12 h. Recovered olefin: 5c,
50 12%; 5e, 20%; 5h, 10% and 20% side product (m/z = 128); 5l,
51 30%. byield of E only; c4 equiv. AgNO2 used; disolated as E/Z
e
mixture; CHCl3 is used as solvent; ffrom trans-4-octene,
52 stereochemistry of the product was determined by COSY/NOESY
53 analysis; gisolated as a mixture of regioisomers. a
54 Isolated yield of the E isomer. Reaction mixtures were analyzed by
Substituents on the position of styrene (4m and 4o) GC-MS and/or 1H-NMR to determine E/Z ratio. olefin (0.5 mmol, 1
55 equiv.), AgNO2 (3 equiv.), TEMPO (0.4 equiv.), molecular sieves 4
had little or no effect on the yield, however, 7:1 E/Z mixture
56 (MS, 150 mg), 70 C, DCE (2 mL), 12 h. byields of E only;
was obtained in 4m. Sterically demanding substrates like c
57 olefin (0.16 mmol), 3.75 equiv AgNO2 and 0.625 equiv TEMPO
2,4,6-trimethylstyrene (4q) was nitrated in 93% yield.
58 MS (80 mg).
Substituent on the -position further increased the steric
59
60 2
ACS Paragon Plus Environment
Page 3 of 5 Journal of the American Chemical Society

1
2
3 The present method is not without limitations. TEMPO; 7c 0.3 mmol olefin, 3.3 equiv AgNO2, 0.5 equiv TEMPO;
4 Conjugated olefins such as buta-1,3-diene-1,1-diyldibenzene 7d 0.25 mmol olefin, 3 equiv AgNO2, 0.4 equiv TEMPO; 7e 0.2
5 (5m) was scarcely reactive and the attempted nitration mmol olefin, 5 equiv AgNO2, 1 equiv TEMPO; bstereochemistry of
6 the product was determined by COSY/NOESY analysis.
resulted the desired nitro product in 10% yield only.
7 Another conjugated olefin, (3-methylbut-3-en-1-yn-1- Derivatives of naturally occurring, pregnenolone (7b),
8 yl)benzene gave the nitro product in 30% yield (5k). and testosterone (7c) were converted to the desired nitro
9 The scarcity of protocols for the nitration of product in good to excellent yields. Disubstituted olefins
10 heteroaromatic olefins emphasizes that they are difficult were selectively nitrated in presence of cyclic internal olefin
11 substrates to carry out nitration reactions. We hypothesized (7b) as was also observed in 5e. Unlike 5e, the cyclic
12 that a highly reactive protocol might be effective for such internal olefin in 7b is buried and is inaccessible for
13 substrates. Consistent with this expectation, pyrazole (6a), nitration. In all cases examined in which stereogenic centers
oxazole (6b) furan (6c) and thiophene (6d and 6e) based were involved, nitration occurred with retention of
14
olefins were nitrated efficiently (Scheme 6). stereochemistry. These examples clearly exhibit the
15
Having established nitration of olefins with relatively beneficial aspects of the current method and indicate that it
16 simple molecules, it was applied to complex natural product can be applied in synthesis of large molecules of
17 derived compounds. Substrate derived from cholestan-3- pharmacological significance and for SAR studies.
18 one was selected for nitration (7a). Though nitration at the Plausible mechanism for nitration of olefin is outlined in
19 terminal site could have produced two diastereomers, Scheme 8. Nitro radical may be generated from AgNO2
20 incorporation of nitro group toward endo cavity leading to under the applied reaction condition. Subsequently a
21 (Z) product would be sterically disfavoured. Thereby, as carbon-centered radical (A) can be generated at the more
22 anticipated, exo-cyclic double bond was nitrated with substituted (or benzylic position), thereby determining
23 complete (E)selectivity and excellent yield (7a, 93%).14 regioselectivity of the reaction solely in terms of stability of
24 Selective nitration can be achieved at styrene by the radical. From A, nitroolefin can be formed via path 1
25 covalently attaching substituted aliphatic olefins in an and/or path 2. TEMPOH will be generated upon abstraction
26 electronically unbiased natural product skeleton. Thus, of H-atom either directly from intermediate A (path 1) or
27 despite having four putative sites of nitration with a from B (path 2). Excess silver nitrite (AgNO2) is likely
28 possibility of forming six isomers at three different olefins, oxidizing TEMPOH back to TEMPO. This is further
29 (E)--nitro styrene product was observed exclusively (7d). supported by the fact that nitration of olefin proceeds
This example highlights the selectivity factors that can be smoothly even with 1 equivalent AgNO2 while using
30
implemented to produce nitroolefins in a complex molecule another equivalent of AgX (X = NO2, OAc, NO3, O0.5) or
31
setting. A diarylether analogue of vitamin E was also Ag2CO3.12 Therefore, silver nitrite is playing a dual role, as
32 nitrated efficiently (7e). source of nitro radical and stoichiometric oxidant. X-ray
33 photoelectron spectroscopy (XPS) indicated formation of
34 Scheme 7. Nitration of complex molecular scaffoldsa
Ag(0) under the present reaction condition.12
35
36 Scheme 8. Proposed mechanism for nitration of olefins
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51 In path 2, TEMPO could intercept the carbon-centered
52 radical to form a TEMPO-alkane-NO2 intermediate (B).
53 Anti-elimination from intermediate B would generate
54 nitroolefin stereoselectively.14 Studer group has recently
55 characterized a series of related adducts wherein exogenous
56 a radical added to olefin with subsequent TEMPO trapping.15
Isolated yield of the E isomer. Reaction mixtures are analyzed by
We were able to trap one such proposed intermediate with
57 GC-MS and/or 1H-NMR to determine E/Z ratio. olefin: AgNO2:
TEMPO (in mmol) 7a 0.4 mmol olefin, 3 equiv AgNO2, 0.5 equiv norbornene as the substrate. Formation of synadduct
58 across the double bond was confirmed by X-ray
TEMPO; 7b 0.14 mmol olefin, 3.2 equiv AgNO2, 0.7 equiv
59
60 3
ACS Paragon Plus Environment
 Journal of the American Chemical Society Page 4 of 5

1
2
3 crystallography (Figure 1). As is evident from the crystal (7) (a) Kurti, L.; Czako, B. Strategic Applications of Named Reactions
4 structure, steric demand of the bicyclic system inhibited in Organic Synthesis; Elsevier Academic Press, 2005. (b)
5 Fioravanti, S.; Pellacani, L.; Tardella, P. A.; Vergari, M. C. Org.
further progress of the reaction to form nitro-norbornene Lett. 2008, 10, 1449.
6 compound. Although such an observation supports path 2 as (8) (a) Kancharla, P. K.; Reddy, Y. S.; Dharuman, S.; Vankar, Y. D. J.
7 the likely mechanism, at present we could not rule out any Org. Chem. 2011, 76, 5832. (b) Taniguchi, T.; Fujii, T.; Ishibashi,
8 of the two pathways we have depicted in Scheme 8. Using H. J. Org. Chem. 2010, 75, 8126 (c) Tinsley, S. W. J. Org. Chem.
9 steady state analysis, it can be shown that both the suggested 1961, 26, 4723. (d) Corey, E. J.; Estreicher, H. J. Am. Chem. Soc.
1978, 100, 6294. (e) Sy, W. W.; By, A. W. Tetrahedron Lett.
10 mechanisms (Scheme 8) are kinetically equivalent and have
1985, 26, 1193. (f) Campos, P. J.; Garcia, B.; Rodriguez, M. A.
11 a partial order (0.4) with respect to TEMPO.12 Detail Tetrahedron Lett. 2000, 41, 979. (g) Jovel, I.; Prateeptongkum, S.;
12 mechanistic studies are presently undergoing in our Jackstell, R.; Vogl, N.; Weckbecker, C.; Beller, M. Adv. Synth.
13 laboratory. Catal. 2008, 350, 2493. (h) Mukaiyama, T.; Hata, E.; Yamada, T.
Chem. Lett. 1995, 505. (i) Suzuki, H.; Mori, T. J. Org. Chem.
14 1997, 62, 6498.
15 (9) Sartori, G.; Ballini, R.; Bigi, F.; Bosica, G.; Maggi, R.; Righi, P.
16 Chem. Rev. 2004, 104, 199.
(10) Manna, S.; Maity, S.; Rana, S.; Agasti, S.; Maiti, D. Org. Lett.
17 2012, 14, 1736.
18 (11) (a) Vogler, T.; Studer, A. Synthesis-Stuttgart 2008, 1979; (b)
19 Tebben, L.; Studer, A. Angew. Chem. Int. Ed. 2011, 50, 5034; (c)
20 Figure 1. ORTEP diagram of plausible intermediate16 Hoover, J. M.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 16901; (d)
He, Z. H.; Kirchberg, S.; Frohlich, R.; Studer, A. Angew. Chem.
21 In summary, a highly selective and efficient protocol for Int. Ed. 2012, 51, 3699.
22 nitration of olefins has been developed by employing (12) See Supporting Information for detailed description.
23 AgNO2/TEMPO under ambient condition.17 This process is (13) Climent, M. J.; Corma, A.; Iborra, S. Chem. Rev. 2011, 111, 1072.
24 practical and a wide array of substrates including aromatic, (14) Intermediate A contains a sp2-radical center (Scheme 8).
Formation of B is likely stereo-determining and may depend on the
25 aliphatic and heteroaromatic olefins can be nitrated in regio
substituents present in A. The (E)--nitro olefins were generated
26 and stereoselective manner. The strategy developed here exclusively possibly due to the stereo electronic requirement of H-
27 can allow olefin nitration as a method for rationalizing atom abstraction by TEMPO (trans-elimination) and/or
28 complex molecule synthesis. thermodynamic stability of the product.
29 Me Me
Acknowledgment. This activity is supported by DST (R/S1/IC N
Me Me
30 24/2011). Financial support received from CSIR-India (fellowship M O M
31 to S. Maity, S.R., T.N.) and IIT Bombay (S. Manna) is gratefully S NO2 NO2
L L
32 acknowledged. D.M. sincerely thanks Dr. Rahul Banerjee (NCL- L M

33
Pune), Mr. Manas Sajjan, Prof. I. N. N. Namboothiri (IIT Bombay)
S
H .O Me
Me
S

and Reviewers for insightful discussions. L, large; M, medium; S, small N

34 Me

35 Supporting Information Available: Experimental Me

procedures and characterization data for all compounds. This Notably, nitration reactions were found to be stereo-convergent e.g.
36 (E)-4-octene produced thermodynamically stable (E)-4-nitrooctene
material is available free of charge via the Internet at
37 (5h) and (Z)-2-hexene produced (E)-2-nitrohexene (5i).
http://pubs.acs.org.
38 Observed stereo chemical outcome of nitration leading to
________________________________________________ product 7a can be rationalized as follows: orientation of the
39 incorporated nitro group at the terminal site should be
References
40 (1) (a) Barrett, A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751. (b) preferentially exo rather than endo to the sterically encumbered
41 Bui, T.; Syed, S.; Barbas, C. F. J. Am. Chem. Soc. 2009, 131, 8758. cavity of fused trans-decalin system. Subsequent elimination/
42 (2) (a) Ishii, T.; Fujioka, S.; Sekiguchi, Y.; Kotsuki, H. J. Am. Chem. oxidation of the exo intermediate would provide E- nitroolefin
Soc. 2004, 126, 9558. (b) Huang, H. B.; Jacobsen, E. N. J. Am. selectively.
43
Chem. Soc. 2006, 128, 7170. (c) Tripathi, C. B.; Kayal, S.;
44 Mukherjee, S. Org. Lett. 2012, 14, 3296.
45 (3) (a) Evans, D. A.; Mito, S.; Seidel, D. J. Am. Chem. Soc. 2007, 129,
46 11583. (b) March, J. Advanced Organic Chemistry; 3rd ed.;
John Wiley & Sons: New York, 1985. (c) Larock, R. C.
47 Comprehensive Organic Transformaions; VCH: New York, 1989.
48 (d) Albrecht, L.; Dickmeiss, G.; Acosta, F. C.; Rodriguez-Escrich,
49 C.; Davis, R. L.; Jorgensen, K. A. J. Am. Chem. Soc. 2012, 134,
(15) (a) Li, Y.; Studer, A., Angew. Chem. Int. Ed. 2012, 51, 8221-8224.
50 2543. (e) Liu, Y. K.; Nappi, M.; Arceo, E.; Vera, S.; Melchiorre,
(b) Hartmann, M.; Li, Y.; Studer, A., J. Am. Chem. Soc. 2012, 134,
P. J. Am. Chem. Soc. 2011, 133, 15212. (f) Arai, T.; Mishiro, A.;
51 Yokoyama, N.; Suzuki, K.; Sato, H. J. Am. Chem. Soc. 2010, 132,
16516-16519.
52 (16) Experimental details of the structure determination can be found
5338. (g) Denmark, S. E.; Thorarensen, A. Chem. Rev. 1996, 96,
in the Supporting Information. CCDC-905717 contains the
53 137.
supplementary crystallographic data for this paper. These data can
54 (4) (a) Basavaiah, D.; Reddy, B. S.; Badsara, S. S. Chem. Rev. 2010,
be obtained free of charge from The Cambridge Crystallographic
110, 5447. (b) Nair, D. K.; Mobin, S. M.; Namboothiri, I. N. N.
55 Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
Org. Lett. 2012, 14, 4580.
56 (17) A provisional patent on this work has been filed IPA
(5) Corma, A.; Serna, P.; Garcia, H. J. Am. Chem. Soc. 2007, 129,
3052/Mum/2012.
57 6358.
(6) Martin, N. J. A.; Ozores, L.; List, B. J. Am. Chem. Soc. 2007, 129,
58
8976.
59
60 4
ACS Paragon Plus Environment
Page 5 of 5 Journal of the American Chemical Society

1
2
3
4
5 For TOC Only
6
7
8 R2 R2
9 AgNO2 / TEMPO
10 NO2
11 R1 DCE, 70 C R1
R3
12
13 R3 [gram-scale]
14 [>40 examples]
15 E only
16
[good FG compatibility]
17 [regio and stereoselective]
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 5
ACS Paragon Plus Environment