Subscriber access provided by the Library Service | Stellenbosch University
Letter
Catalytic Intramolecular Acylsulfenylation of Activated Alkenes: Enantioselective Synthesis of 3,3-Disubstituted Quinoline-2,4-diones Wei Liu, Huan-Qing Zhang, and Wei-Wei Liao ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b01412 • Publication Date (Web): 11 May 2018 Downloaded from http://pubs.acs.org on May 12, 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 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
Catalytic Intramolecular Acylsulfenylation of Activated Alkenes: Enantioselective Synthesis of 3,3-Disubstituted Quinoline-2,4-diones Wei Liu, Huan-Qing Zhang, Wei-Wei Liao* Department of Organic Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
ABSTRACT: An asymmetric intramolecular acylsulfenylation approach is presented. By combining catalytic amount of chiral amino diether (1S,2S)-L6 and RSLi, a wide range of 3,3-disubstituted quinoline-2,4-dione derivatives incorporating allcarbon quaternary stereocenters could be accessed in excellent yields and enantioselectivities in a catalytically atomeconomic fashion. The concept relies on an asymmetric SMA/aldol type sequence by employing thioester as a bifunctional carbonyl resource, which enabled the construction of the cyclic scaffolds smoothly. KEYWORDS: asymmetric catalysis, cyclization, organosulfur compounds, quaternary stereocenter, atom-economy
INTRODUCTION: Development of efficient asymmetric approach to access enantioenriched compounds is of importance not only to modern organic chemistry, 1 but also to pharmaceutical and agricultural chemistry. 2 3,3Disubstituted quinoline-2,4-diones and derivatives are very interesting 1,3-dicarbonyl scaffolds, presenting in quinolone alkaloids and arose increasing attention for the development of therapeutic agents. 3 Although appreciable progress has been achieved in the synthesis of these scaffolds,4 the enantioselective approaches for the construction of chiral 3,3-disubstituted quinoline-2,4-diones are scarce, and limited in the substrate-control stereoselective processes, presumably due to the challenge of the construction of all-carbon quaternary stereocenter. 5 For example, Dewynter et al. and Carlier et al. reported an enantioselective deprotonative ring contraction approach from enantioenriched substrates to prepare these scaffolds, respectively. 6 In addition, Feng et al. reported an elegant catalytic asymmetric ring-expansion reaction of isatins and α-alkyl-α-diazoesters, but for the preparation of chiral quinoline-2,3(1H,4H)-dione derivatives. 7 Given that the promising biological activities of these scaffolds were displayed in medicinal chemistry and pharmacological profile may be configuration-dependent,2b the development of efficient strategies for asymmetric catalytic synthesis of these frameworks are highly desirable. Organosulfur compounds are widely present in nature and various biological systems, 8 and can also serve as useful synthetic tool to access a diverse array of carbocycles and heterocyclic frameworks bearing sulfur moieties. 9 Among them, sulfa-Michael addition (SMA) triggered tandem reactions, in which generated enolate intermediate can subsequently react with electrophiles in an intramolecular fashion to give a diversity of cyclic organosulfur compounds, has acquired wide application in organic synthesis and in biological processes. 10 Typically, in the SMA/aldol type sequence, the stoichiometric sulfur nucle-
ophile and the installation of a highly reactive carbonyl group such as aldehyde group are required to enable a SMA/aldol process to proceed well, which can provide various hydroxyl substituted cyclic organosulfur compounds in an intramolecular fashion (Scheme 1a and 1b). However, the alternative possibility that the inclusion of carbonyl group with Previous work: SMA/aldo l tandem (a) O EWG
H
RS HO
R
R RS
EWG (b)
O R'
R1
EWG
S
HO
n R''
R''
This work: asymmetric catalytic acylsu lfenylation (c) O O RS-Li ( cat.) SR SR ligand (cat.) Ar R2 R1 asym. N O
R2
O
* *
RS
R' n
S
EWG R1
O
*
Ar N R1
* SR
O
Scheme 1. Synthetic Strategy leaving unit in this tandem sequence would enable the construction of cyclic scaffold incorporating 1,3-dicarbonyl substituted all-carbon quaternary stereocenter, has received less attention. We envisaged that the inclusion of a thioester as a bifunctional carbonyl resource, would not only address these issues, but also enable an intramolecular asymmetric acylsulfenylation of electron-deficient alkenes to deliver cyclic scaffold incorporating 1,3dicarbonyl substituted all-carbon quaternary stereocenter in a catalytically atom-economic fashion. 11 Recently, we reported a diastereoselective synthesis of tetrahydropyrrolo[2,1-a]isoquinoline derivatives bearing sulfur moiety from diastereomeric pure substrates by implementing
ACS Paragon Plus Environment
ACS Catalysis 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
this nucleophilic acylsulfenylation approach.12 However, the development of catalytic enantioselective version of this approach from non-chiral substrates to access the enantioenriched cyclic compounds incorporating 1,3dicarbonyl substituted all-carbon quaternary stereocenters is challenging and undeveloped. Herein, we report an asymmetric nucleophilic acylsulfenylation approach to prepare 3,3-disubstituted quinoline-2,4-dione derivatives with high enantioselectivities in a catalytically atomeconomic fashion (Scheme 1c). ************************************************** Table 1. Selected Optimization of Reaction Conditions a
entry
R1
ligand
M
t (h)
yield (%) b
e.r. c
1
Me
L1
Li
12
97 (2a)
26/74
2
Me
L2
Li
12
90 (2a)
40/60
3
Me
L3
Li
12
51 (2a)
61/39
4
Me
L4
Li
12
91 (2a)
61/39
5
Me
L5
Li
12
53 (2a)
74/26
6
Me
L6
Li
5
94 (2a)
89/11
7
Me
L7
Li
5
96 (2a)
48/52
8
Me
L8
Li
5
97 (2a)
50/50
9
Me
L9
Li
5
95 (2a)
69/31
10
Me
L10
Li
5
95 (2a)
69/31
11
Me
L11
Li
5
96 (2a)
33/67
12
Me
L12
Li
5
97 (2a)
64/36
13 d
Me
L6
Na
12
