- Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction
-
In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.
- Fang, Sen-Biao,Li, Hui-Jing,Nan, Xiang,Wu, Rui,Wu, Yan-Chao,Zhang, Jing,Zhang, Zhi-Zhou
-
-
- Pd-catalyzed amidation of 1,3-diketones with CO and azidesviaa nitrene intermediate
-
An efficient Pd-catalyzed amidation of 1,3-diketones has been developed using carbon monoxide and organic azides. This reaction provides a step-economic approach to produce β-ketoamides from readily available compounds under mild ligand-, oxidant-, and base-free conditions. The mechanistic studies showed that the reaction occurred through anin situgenerated isocyanate intermediate.
- Gu, Zheng-Yang,Chen, Jie,Xia, Ji-Bao
-
supporting information
p. 11437 - 11440
(2020/10/12)
-
- Rh(III)-Catalyzed C(8)-H Activation of Quinoline N-Oxides: Regioselective C-Br and C-N Bond Formation
-
A highly efficient and regioselective Rh(III)-catalyzed protocol for C8-bromination and amidation of quinoline N-oxide was developed. The transformation was found to be successful up to gram scale with excellent functional group tolerance and wide substrate scope. The mechanistic study revealed five-membered rhodacycle with quinoline N-oxide as a key intermediate for regioselective C8-functionalization. In addition, NFSI (N-fluorobis(phenylsulfonyl)-imide) was explored as an amidating reagent for C8-amidation of quinoline N-oxide for the first time.
- Dhiman, Ankit Kumar,Gupta, Shiv Shankar,Sharma, Ritika,Kumar, Rakesh,Sharma, Upendra
-
p. 12871 - 12880
(2019/11/02)
-
- Intermolecular C?H Amidation of (Hetero)arenes to Produce Amides through Rhodium-Catalyzed Carbonylation of Nitrene Intermediates
-
Amide bond formation is one of the most important reactions in organic chemistry because of the widespread presence of amides in pharmaceuticals and biologically active compounds. Existing methods for amides synthesis are reaching their inherent limits. Described herein is a novel rhodium-catalyzed three-component reaction to synthesize amides from organic azides, carbon monoxide, and (hetero)arenes via nitrene-intermediates and direct C?H functionalization. Notably, the reaction proceeds in an intermolecular fashion with N2 as the only by-product, and either directing groups nor additives are required. The computational and mechanistic studies show that the amides are formed via a key Rh-nitrene intermediate.
- Yuan, Si-Wen,Han, Hui,Li, Yan-Lin,Wu, Xueli,Bao, Xiaoguang,Gu, Zheng-Yang,Xia, Ji-Bao
-
supporting information
p. 8887 - 8892
(2019/05/29)
-
- Palladium(0)-Catalyzed Carbonylative Synthesis of N-Acylsulfonamides via Regioselective Acylation
-
N-Acylsulfonamides represent an important bioisostere of carboxylic acids that allow for greater molecular elaboration and enhanced hydrogen bonding capabilities. Herein, we present a mild and convenient palladium(0)-catalyzed synthesis of N-acylsulfonamides via the carbonylative coupling of sulfonyl azides and electron-rich heterocycles. The reaction proceeds via in situ generation of a sulfonyl isocyanate followed by regioselective acylation of an indole or pyrrole nucleophile. This approach has been used to synthesize 34 indole- and pyrrole-substituted N-acylsulfonamides in yields of up to 95%. Importantly, this process is ligand-free and compatible with an ex situ solid CO source and requires only slightly elevated temperatures, making it a highly attractive method for the preparation of this important class of compounds. This study further investigated the possibility of labeling N-acylsulfonamides with carbon-11 to facilitate biological evaluation and in vivo studies with positron emission tomography.
- Schembri, Luke S.,Eriksson, Jonas,Odell, Luke R.
-
p. 6970 - 6981
(2019/06/14)
-
- Ligand-Free, Quinoline N-Assisted Copper-Catalyzed Nitrene Transfer Reaction to Synthesize 8-Quinolylsulfimides
-
An efficient copper-catalyzed, quinolyl N-directed nitrene transfer reaction to 8-quinolylsulfides was described. A variety of 8-quinolylsulfimides with different functional groups were synthesized in moderate to high yields. The obtained 8-quinolylsulfimides were proved to be promising novel type of bidentate ligands in Pd(II)-catalyzed allylic alkylation.
- Xiao, Xinsheng,Huang, Sanping,Tang, Shanshan,Jia, Guokai,Ou, Guangchuan,Li, Yangyan
-
p. 7618 - 7629
(2019/06/27)
-
- Nitroacenaphthene as a New Photocatalyst for the Synthesis of Sulfonyl Amidines
-
A small molecule, namely nitroacenaphthene, is reported for the first time as a recyclable visible-light photocatalyst for the construction of the C=N bond from sulfonyl azides and amines. This scalable, site-selective protocol provides a convenient way to access various sulfonyl amidines under mild conditions. Two reaction pathways are proposed, according to different transformation patterns.
- Chen, Ming,Jian, Yong,Xia, Wujiong,Yang, Chao
-
p. 4425 - 4433
(2019/11/21)
-
- Palladium-Catalyzed One-Pot Synthesis of N -Sulfonyl, N -Phosphoryl, and N -Acyl Guanidines
-
An efficient palladium-catalyzed cascade reaction of azides with isonitrile and amines is presented; it offers an alternative facile approach toward N -sulfonyl-, N -phosphoryl-, and N -acyl-functionalized guanidines in excellent yield. These series of substituted guanidines exhibit potential biological and pharmacological activities. In addition, the less reactive intermediate benzoyl carbodiimide could be isolated by silica gel column flash chromatography in moderate yield.
- Qiao, Guanyu,Zhang, Zhen,Huang, Baoliang,Zhu, Liu,Xiao, Fan,Zhang, Zhenhua
-
supporting information
p. 330 - 340
(2018/01/12)
-
- Iridium(III)-Catalyzed Selective and Mild C-H Amidation of Cyclic N-Sulfonyl Ketimines with Organic Azides
-
A general protocol for iridium catalyzed direct C?H amidation of cyclic N-sulfonyl ketimines using sulfonyl, acyl and aryl azides as nitrogen source is reported herein. The reaction takes place at room temperature with acyl and aryl azides, while an elevated temperature needed with sulfonyl azides to furnish aminated sultams in excellent yields with complete chemo and regioselectivity, thus providing a robust and environmentally benign process to the synthesis of aminosultams. (Figure presented.).
- Maraswami, Manikantha,Chen, Gang,Loh, Teck-Peng
-
supporting information
p. 416 - 421
(2017/11/13)
-
- Synthesis of Sulfonyl Azides via Lewis Base Activation of Sulfonyl Fluorides and Trimethylsilyl Azide
-
A protocol for the efficient conversion of sulfonyl fluorides into sulfonyl azides through Lewis base activation is described. The in situ generated sulfonyl azides are efficient diazo-transfer agents, affording diazo compounds and primary azides in excellent yields.
- Barrow, Andrew S.,Moses, John E.
-
supporting information
p. 1840 - 1843
(2016/07/16)
-
- Iridium(III)-Catalyzed Direct C-H Sulfonamidation of 2-Aryl-1,2,3-triazole N-Oxides with Sulfonyl Azides
-
We have developed a method for the direct sulfonamidation of 2-aryl-1,2,3-triazole N-oxides using sulfonyl azides as the amino source to release molecular nitrogen as the sole by-product. This protocol exhibits excellent functional group tolerance and proceeds efficiently under external oxidant-free conditions. Various 2-(2-sulfonamidoaryl)-1,2,3-triazoles were prepared in up to 97% yields for 25 examples with excellent regioselectivity.
- Zhu, Bingfeng,Cui, Xiuling,Pi, Chao,Chen, Dong,Wu, Yangjie
-
supporting information
p. 326 - 332
(2016/02/14)
-
- Product-Derived Bimetallic Palladium Complex Catalyzes Direct Carbonylation of Sulfonylazides
-
A novel product-derived bimetallic palladium complex catalyzes a sulfonylazide-transfer reaction with the σ-donor/π-acceptor ligand CO, and is advantageous given its broad substrate scope, high efficiency, and mild reaction conditions (atmospheric pressure of CO at room temperature). This methodology provides a new approach to sulfonylureas, which are present in both pharmaceuticals and agrochemicals. The synthesis of Glibenclamide on a gram scale further revealed the practical utility of this procedure. Mechanistically, the generation of a bridged bimetallic palladium species derived from the product sulfonylurea is disclosed as the crucial step for this catalytic cycle.
- Zhao, Jin,Li, Zongyang,Song, Shaole,Wang, Ming-An,Fu, Bin,Zhang, Zhenhua
-
supporting information
p. 5545 - 5549
(2016/05/09)
-
- A Direct Access to 7-Aminoindoles via Iridium-Catalyzed Mild C-H Amidation of N-Pivaloylindoles with Organic Azides
-
Ir(III)-catalyzed regioselective direct C-7 amidation of indoles in reaction with organic azides has been developed. While its efficiency was varied by the choice of N-directing groups, N-pivaloylindoles were most effective in undergoing the desired amidation at room temperature over a broad range of substrates. The reaction was scalable, and deprotection of the chelation group was also facile.
- Kim, Youyoung,Park, Juhyeon,Chang, Sukbok
-
supporting information
p. 1892 - 1895
(2016/05/19)
-
- Direct C-H amidation of benzoic acids to introduce meta- and para-amino groups by tandem decarboxylation
-
The Ir-catalyzed mild C-H amidation of benzoic acids with sulfonyl azides was developed to give reactions with high efficiency and functional-group compatibility. Subsequent protodecarboxylation of ortho-amidated benzoic acid products afforded meta- or para-substituted (N-sulfonyl)aniline derivatives, the latter being inaccessible by other C-H functionalization approaches. The decarboxylation step was compatible with the amidation conditions, enabling a convenient one-pot, two-step process. Without a trace: Carboxylic acids are used as traceless directing groups in the Ir-catalyzed direct C-H amidation of arenes with sulfonyl azides under mild conditions. The tandem protodecarboxylation of the ortho-amidated benzoic acid products afforded meta- or para-substituted (N-sulfonyl)anilines, which are difficult to obtain by other C-H functionalization approaches.
- Lee, Donggun,Chang, Sukbok
-
supporting information
p. 5364 - 5368
(2015/03/30)
-
- Iridium-Catalyzed Direct C-H Sulfamidation of Aryl Nitrones with Sulfonyl Azides at Room Temperature
-
Ir(III)-catalyzed direct C-H sulfamidation of aryl nitrones has been developed to synthesize various sulfamidated nitrones in moderate to excellent yields with excellent regioselectivity and broad functional group tolerance. This transformation could proceed smoothly at room temperature with low catalyst loading in the absence of external oxidants, acids, or bases. Molecular nitrogen was released as the sole byproduct, thus providing an environmentally benign sulfamidation process. And this protocol could efficiently apply to synthesize the substituted benzisoxazoline via one-step transformation from the product.
- Pi, Chao,Cui, Xiuling,Wu, Yangjie
-
p. 7333 - 7339
(2015/08/18)
-
- Iridium-catalyzed direct ortho-C-H amidation of benzoic acids with sulfonylazides
-
A mild and efficient iridium-catalyzed ortho-C-H amidation with sulfonyl azides by weakly coordinating carboxylic acid was demonstrated, which provided a novel approach to anthranilic acid derivatives.
- Wei, Ming-E,Wang, Lian-Hui,Li, Yu-Dong,Cui, Xiu-Ling
-
supporting information
p. 1336 - 1340
(2015/10/28)
-
- Synthesis of 1,2-amino alcohols via catalytic C-H amidation of sp3 methyl C-H bonds
-
Herein a new synthetic route to 1,2-amino alcohols is presented by using C-H amidation of sp3 methyl C-H bonds as a key step. Readily available alcohols were employed as starting materials after converting them to removable ketoxime chelating g
- Kang, Taek,Kim, Heejeong,Kim, Jeung Gon,Chang, Sukbok
-
supporting information
p. 12073 - 12075
(2014/12/11)
-
- Iridium-catalyzed direct C-H amidation with weakly coordinating carbonyl directing groups under mild conditions
-
An iridium-catalyzed direct C-H amidation of weakly coordinating substrates, in particular of those bearing ester and ketone groups, under very mild conditions has been developed. The observed high reaction efficiency was achieved by the combined use of acetic acid and lithium carbonate as additives. Copyright
- Kim, Jinwoo,Chang, Sukbok
-
supporting information
p. 2203 - 2207
(2014/03/21)
-
- Iridium-catalyzed intermolecular amidation of sp3 C-H bonds: Late-stage functionalization of an unactivated methyl group
-
Reported herein is the iridium-catalyzed direct amidation of unactivated sp3 C-H bonds. With sulfonyl and acyl azides as the amino source, the amidation occurs efficiently under mild conditions over a wide range of unactivated methyl groups with high functional group tolerance. This procedure can be successfully applied for the direct introduction of an amino group into complex compounds and thus can serve as a powerful synthetic tool for late-stage C-H functionalization.
- Kang, Taek,Kim, Youngchan,Lee, Donggun,Wang, Zhen,Chang, Sukbok
-
supporting information
p. 4141 - 4144
(2014/04/03)
-
- Access to the aeruginosin serine protease inhibitors through the nucleophilic opening of an oxabicyclo[2.2.1]heptane: Total synthesis of microcin SF608
-
Serine proteases play key roles in many biological processes and are associated with several human diseases such as thrombosis or cancer. During the search for selective inhibitors of serine proteases, a family of linear peptides named the aeruginosins was discovered in marine cyanobacteria. We herein report an entry route into the synthetically challenging core fragment of these natural products. Starting from the common oxabicyclic building block 11, we accessed the octahydroindole core of the aeruginosins, exemplified by the total synthesis of microcin SF608 (2). Key to the synthetic strategy is a highly efficient nucleophilic opening of an oxabicyclo[2.2.1]heptane producing the hydroindole motif of microcin SF608. Moreover, during the synthetic efforts we have observed an unusual regioselective epoxide reduction. Detailed experimental studies of this reaction led us to propose a mechanistic rationale involving intramolecular hydrogen atom delivery by a carbamate NH group to control the regioselectivity of the homolytic epoxide cleavage. Expect the unexpected! An entry route to the aeruginosin protease inhibitors is reported and showcased on the total synthesis of microcin SF608 (see scheme). Detailed experimental studies of an unusual regioselective epoxide reduction observed during this synthesis suggests a mechanistic rationale for this transformation involving intramolecular hydrogen atom delivery by a carbamate NH to direct the regioselectivity of the homolytic epoxide cleavage.
- Diethelm, Stefan,Schindler, Corinna S.,Carreira, Erick M.
-
supporting information
p. 6071 - 6080
(2014/05/20)
-
- Iridium(III)-Catalyzed C H Amidation of Arylphosphoryls Leading to a P-Stereogenic Center
-
Direct C H amidation of arylphosphoryl compounds has been developed by using an IrIIIcatalyst system under mild conditions. A wide range of substrates could be employed with high functional-group tolerance. This procedure was successfully applied for the first time to the asymmetric reaction giving rise to a P-chirogenic center with a high diastereomeric ratio of up to 19:1 (90 % de).
- Gwon, Donghyeon,Lee, Donggun,Kim, Jiyu,Park, Sehoon,Chang, Sukbok
-
supporting information
p. 12421 - 12425
(2016/08/25)
-
- Synthesis of 2-Aryl-2 H-benzotrizoles from azobenzenes and N-sulfonyl azides through sequential rhodium-catalyzed amidation and oxidation in one pot
-
An efficient synthetic method of 2-aryl-2H-benzotriazoles from nonprefunctionalized azobenzenes and N-sulfonyl azides via sequential Rh-catalyzed amidation (C-N bond formation) and oxidation (N-N bond formation) with PhI(OAc)2 in one pot is reported.
- Ryu, Taekyu,Min, Jiae,Choi, Wonseok,Jeon, Woo Hyung,Lee, Phil Ho
-
supporting information
p. 2810 - 2813
(2014/06/23)
-
- Rhodium(III)-catalyzed intermolecular amidation with azides via C(sp 3)-H functionalization
-
The amidation reactions of 8-methylquinolines with azides catalyzed by a cationic rhodium(III) complex proceed efficiently to give quinolin-8- ylmethanamine derivatives in good yields via C(sp3)-H bond activation under external oxidant-free conditions. A catalytically competent five-membered rhodacycle has been isolated and characterized, revealing a key intermediate in the catalytic cycle.
- Wang, Nuancheng,Li, Renhe,Li, Liubo,Xu, Shansheng,Song, Haibin,Wang, Baiquan
-
p. 5379 - 5385
(2014/06/23)
-
- Regioselective introduction of heteroatoms at the C-8 position of quinoline N-oxides: Remote C-H activation using N-oxide as a stepping stone
-
Reported herein is the metal-catalyzed regioselective C-H functionalization of quinoline N-oxides at the 8-position: direct iodination and amidation were developed using rhodium and iridium catalytic systems, respectively. Mechanistic study of the amidation revealed that the unique regioselectivity is achieved through the smooth formation of N-oxide-chelated iridacycle and that an acid additive plays a key role in the rate-determining protodemetalation step. While this approach of remote C-H activation using N-oxide as a directing group could readily be applied to a wide range of heterocyclic substrates under mild conditions with high functional group tolerance, an efficient synthesis of zinquin ester (a fluorescent zinc indicator) was demonstrated.
- Hwang, Heejun,Kim, Jinwoo,Jeong, Jisu,Chang, Sukbok
-
supporting information
p. 10770 - 10776
(2014/08/18)
-
- One-pot synthesis of sulfonamides and sulfonyl azides from thiols using chloramine-T
-
A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols was accomplished by oxidation with chloramine-T (=N-chlorotosylamide=N-chloro-4- methylbenzenesulfonamide), tetrabutylammonium chloride (Bu4NCl), and H2O. The sulfonyl chlorides were then further allowed to react with excess amine or NaN3 in the same pot.
- Maleki, Behrooz,Hemmati, Saba,Tayebee, Reza,Salemi, Sirous,Farokhzad, Yasaman,Baghayeri, Mehdi,Zonoz, Farrokhzad Mohammadi,Akbarzadeh, Elahe,Moradi, Rohollah,Entezari, Azam,Abdi, Mohammad Reza,Ashrafi, Samaneh Sedigh,Taimazi, Fereshteh,Hashemi, Majid
-
p. 2147 - 2151
(2013/12/04)
-
- Ruthenium-catalyzed direct C-H amidation of arenes including weakly coordinating aromatic ketones
-
C-H activation: The ruthenium-catalyzed direct sp2 C-H amidation of arenes by using sulfonyl azides as the amino source is presented (see scheme). A wide range of substrates were readily amidated including arenes bearing weakly coordinating groups. Synthetic utility of the thus obtained products was demonstrated in the preparation of biologically active heterocycles. Copyright
- Kim, Jiyu,Kim, Jinwoo,Chang, Sukbok
-
supporting information
p. 7328 - 7333
(2013/06/27)
-
- Ru(ii)-catalyzed intermolecular ortho-C-H amidation of aromatic ketones with sulfonyl azides
-
Ru(ii)-catalyzed intermolecular ortho-C-H amidation of weakly coordinating aromatic ketones with sulfonyl azides is reported. The developed reaction protocol can be extended to various substituted aromatic ketones to afford a wide range of desired C-N bond formation products in good yields.
- Bhanuchandra,Ramu Yadav,Rit, Raja K.,Rao Kuram, Malleswara,Sahoo, Akhila K.
-
supporting information
p. 5225 - 5227
(2013/06/27)
-
- Rhodium-catalyzed intermolecular amidation of arenes with sulfonyl azides via chelation-assisted C-H bond activation
-
We report the direct amidation of arene C-H bonds using sulfonyl azides as the amino source to release N2 as the single byproduct. The reaction is catalyzed by a cationic rhodium complex under external oxidant-free conditions in the atmospheric environment. A broad range of chelate group-containing arenes are selectively amidated with excellent functional group tolerance, thus opening a new avenue to practical intermolecular C-N bond formation.
- Kim, Ji Young,Park, Sae Hume,Ryu, Jaeyune,Cho, Seung Hwan,Kim, Seok Hwan,Chang, Sukbok
-
supporting information; experimental part
p. 9110 - 9113
(2012/07/14)
-
- Convenient one-pot synthesis of sulfonamides and sulfonyl azides from thiols using N -chlorosuccinimide
-
A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols is accomplished by oxidation with N-chlorosuccinimide (NCS), tetrabutylammonium chloride, and water. The sulfonyl chlorides are then further allowed to react with excess amine or sodium azide in the same reaction vessel. Georg Thieme Verlag Stuttgart - New York.
- Veisi, Hojat,Ghorbani-Vaghei, Ramin,Hemmati, Saba,Mahmoodi, Jafar
-
p. 2315 - 2320
(2011/10/13)
-
- Thermolysis of Sulfonyl Azides Bearing Nucleophilic Neighboring Groups. A Search for Anchimeric Assistance
-
In a search for anchimeric assistance by n- or ?-donor neighboring groups in sulfonyl azide decompositions, 25 sulfonyl azides have been prepared and thermolyzed in 1-chloronaphthalene.First-order rate constants at 135 and 165 deg C were determined by mea
- McManus, Samuel P.,Smith, Maurice R.,Abramovitch, Rudolph A.,Offor, Mercy N.
-
p. 683 - 687
(2007/10/02)
-
- Simple Spectrophotometric Method for Determination of Carbonyl and Sulfonyl Chlorides
-
The method presented is based on the reaction of carbonyl and sulfonyl chlorides with sodium azide in water-acetone solution at room temperature for 10 min; the excess of azide is determined spectrophotometrically after conversion to a red complex with Fe3+.Reactive anhydride can also be determined by this method.The application of the new method was demonstrated for monitoring conversion of sulfonyl chlorides to sulfonyl fluorides and for controlling the acylation of amino compounds with phthaloyl-L-glutamic anhydride.
- Siewinski, Maciej,Kuropatwa, Marianna,Szewczuk, Apolinary
-
p. 2882 - 2884
(2007/10/02)
-
- Substitution Reactions of Alkanesulfonyl Derivatives: Direct Substitution vs. Elimination-Addition Mechanisms in Substitution Reactions of Alkyl α-Disulfones
-
The reactions of a series of alkyl and aralkyl α-sulfones, RSO2SO2R ( R = Me, n-Bu, i-Pr, ArCH2) with a variety of nucleophiles in aqueous dioxane have been examined.Both rates of reaction and whether a given reaction takes place by an elimination-addition (sulfene intermediate) or a direct substitution (attack of nucleophile on SO2 group of α-sulphone) mechanism have been determined.The great majority of substitution reactions of alkyl α-disulfones take place via an elimination-addition mechanism (eq 3a), with formation of a sulphene from the α-disulphone being rate determining.Only when nucleophile is one, like azide ion, that is weakly basic while still being a good nucleophile is a direct substitution the preferred pathway.Even with azide the reaction pathway changes to elimination-addition when the acidity of the hydrogens on the carbon adjacent to the sulfonyl group is increased sufficiently, as in (PhCH2SO2)2.Comparison of rates of elimination of α-disulphones (R'CH2SO2)2 with rates of base-catalyzed hydrogen exchange of the corresponding trifluoromethyl sulfones R'CH2SO2CF3 indicates that formation of sulfenes from α-disulfones involves either an irreversible E1cB or a very E1cB-like E2 mechanism, a conclusion that is also supported by the observed variation of the rate of elimination of RR'CHSO2SO2R'' with changes in R and R'.Comparison of the behavior of an alkyl α-disulfone with that of the corresponding alkanesulfonyl chloride reveals that changing Y in RCH2SO2Y from RSO2 to Cl causes direct substitution to be able to compete much more effectively with elimination-addition.Kinetic studies show that this arises because, for a given nucleophile, (a) elimination-addition is 5-10 times slower for the alkanesulfonyl chloride than for the α-disulfone while (b) the rate of direct substitution is 5-10 times faster for the sulfonyl chloride.The origin of these rate differences is discussed and explained.
- Fang, Lieh-pao O.,Kice, John L.
-
p. 1137 - 1145
(2007/10/02)
-