Diverse Transformation of Vinyl Azides with 2,2,6,6 ... - ACS Publications

Jun 6, 2018 - ...
0 downloads 0 Views 299KB Size
Subscriber access provided by Kaohsiung Medical University

Article

Diverse Transformation of Vinyl Azides with 2,2,6,6-Tetramethyl-N-oxopiperidinium Jia-Li Liu, Shu-Wei Wu, Qing-Yan Wu, and Feng Liu J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00954 • Publication Date (Web): 06 Jun 2018 Downloaded from http://pubs.acs.org on June 6, 2018

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 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 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.

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 38 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

The Journal of Organic Chemistry

Diverse Transformation of Vinyl Azides with 2,2,6,6-Tetramethyl-N-oxopiperidinium Jia-Li Liu,†,# Shu-Wei Wu,†,# Qing-Yan Wu,† and Feng Liu*,†,§ †

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Department of Medicinal Chemistry,

College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, People’s Republic of China §

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese

Academy of Sciences, 345 Lingling Road, Shanghai 200032, People’s Republic of China #

These authors contributed equally to this work

O

O O

R1 N3 R2

R1

R1

N

or

R2

N O

N H

O

N

R2

(R = H)

ROH

RO

N3

or R 1

O

N

R2 (R = Alkyl)

ABSTRACT A 2,2,6,6-tetramethyl-N-oxopiperidinium (TEMPO+)-mediated three-component diverse transformation of vinyl azides under metal-free conditions is described. The reaction protocols are operationally simple and conducted at ambient temperature, allowing to access various TEMPO-trapped ketones, amides, and -alkoxyalkyl azides.

Preliminary

mechanistic

studies

indicate

that

an

alkene

radical

cation-mediated radical-radical cross-coupling C–O bond formation could be

ACS Paragon Plus Environment

The Journal of Organic Chemistry 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

Page 2 of 38

involved. INTRODUCTION The association of an electron-rich (a donor) with an electron-deficient (an acceptor) molecule, yields an electron donor-acceptor (EDA) complex, that can bring about an electron transfer event without the need of any photocatalyst.1 Although the physicochemical properties of EDA complexes have been extensively studied since the 1950s,2 their use in chemical synthesis is still under-explored. In recent years, a variety of novel methods involving EDA complexes have been developed for useful transformations.3 These remarkable achievements show possibilities for new reaction design through EDA complex in organic synthesis. As a demonstration of this potential, we report herein a facile, room-temperature, diverse transformation of vinyl azides using 2,2,6,6-tetramethyl-N-oxopiperidinium (TEMPO+) as the electron acceptor. Scheme 1. Electrophilic Transformation of Vinyl Azides

N3 R2

R1 1

N

E

N2

-N 2 R2

R1

R2 R1 N E

8

7E ROH RO N 3 R1 9

O E

R2

R1

E

N H

R2 10

Recently, vinyl azides,4 a class of functionalized alkenes with unique intrinsic reactivity, have emerged as important synthons for developing novel synthetic

ACS Paragon Plus Environment

Page 3 of 38 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

The Journal of Organic Chemistry

methods.5 As an electron-rich enamine-type molecule, vinyl azide 1 is liable to react with an electrophile to form an iminodiazonium ion intermediate 7.6 The subsequent step is either the Schmidt-type rearrangement to give a nitrilium ion 8 that could be intercepted by water to produce an amide 10 or interruption of the rearrangement by an alcohol to yield an α-alkoxy-β- haloalkyl azide 9 (Scheme 1).6a On the other hand, we found that vinyl azide 1 could interact with an electron-poor molecule, such as Selectfluor

(1-chloromethyl-4-fluoro-1,4-diazoniabicyclo

[2.2.2]octane

bis(tetrafluoroborate)), to form an EDA complex.7 A single electron transfer (SET) process took place subsequently, generating an alkene radical cation 11, followed by fluorine atom transfer and nucleophilic addition with water to give -fluoroketone 12 (Scheme 2).7a Scheme 2. EDA Complex-Enabled Transformation of Vinyl Azides N Previous work:

N F

Cl 2BF4

SelectFluor

O R1

N3 F

N N

SET, H 2 O

Cl

R2

R2 N3

12

N3

EDA complex R2

R1

V ia:

R2

R1 11

1

R1

O

R1

O N This study:

O

O

N3 R2

F

R1

EDA

R1

N

or

R2

SET, ROH

2

N O ClO 4

O

R1

O

N

N

R2

(R = H)

RO N 3

(TEMPO ClO4 )

N H

3

(R = Alkyl)

R2 4

Within the realm of open-shell chemistry, the alkene radical cations show a combination of free radical and cation chemistry that confers an interesting manner of reactivity on them.8 As excellent oxidants, TEMPO+ and its analogs are widely used for the oxidation of alcohols.9 Recently, a charge-transfer (CT) complex

ACS Paragon Plus Environment

The Journal of Organic Chemistry 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

TEMPO–ClO2 was identified by Yamamoto and coworkers.10 Our very recent report also demonstrated that TEMPO+ could interact with vinyl ether to form an EDA complex.11 Thus, we wondered if we might be able to access the reactive open shell radical cation via a thermal-activated electron transfer from vinyl azide to TEMPO+ as Selectfluor did.7 In the present study, we further advance the concept of EDA complex and aim to diversely convert vinyl azides into TEMPO-trapped ketones 2, amides 3, and -alkoxyalkyl azides 4 (Scheme 2).

RESULTS AND DISCUSSION At the outset, we used 4-(1-azidovinyl)biphenyl as the model substrate to screen the reaction conditions (Table 1). To our delight, we observed the TEMPO-trapped ketone 2a in 89% NMR yield and only trace amount of 3a and 5a were found when using THF as the solvent (entry 1). Other organic solvents were also examined (entries 2–10), identifying THF as the best one in terms of chemical yield of 2a. It should be noted that around 40% yield of amide 3a was detected in the examples of DCE and DCM (entries 8 and 10). Subsequently, examination of the amount of external water showed that 2 equivalents of water could give the highest chemical yield of 2a (entries 11–13). In order to neutralize the byproduct HClO4, inorganic base (NaHCO3 or Na2CO3) was added, but the chemical yields dropped (entries 14–15). The reaction proceeded smoothly in the dark as well though the yield shrank a little (entry 16 vs. entry 12).

ACS Paragon Plus Environment

Page 4 of 38

Page 5 of 38 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

The Journal of Organic Chemistry

Table

1.

Optimization

of

the

Reaction

Conditions

for Synthesis

of

TEMPO-trapped Ketones a O O N3 TEMPO ClO 4 (1.5 equiv) Ph

solvent, rt

= TMP

Ph 2a + H N

1a

N

OTMP

OTMP O

Ph

N3 N3 Ph

3a

a

Entry

Solventb

H2O (equiv)

T (h)

1 2 3 4 5 6 7 8 9 10 11 12 13 14d 15e 16f

THF acetone 1,4-dioxane DMF DMSO EtOAc CH3CN DCE PhCl DCM THF THF THF THF THF THF

– – – – – – – – – – 1 2 4 2 2 2

6 0.5 6 4.5 6 6 0.5 4.5 6 1 6 6 6 6 6 12

5a

Yield (%)c 2a

3a

5a

89 85 77 74 0 63 59 33 25 16 88 97 76 51 51 71