Palladium-Catalyzed Cï£¿C Coupling of Aryl Halides with Isocyanides: An Alternative Method for...

DOI: 10.1002/adsc.201200212

Palladium-Catalyzed C�C Coupling of Aryl Halides withIsocyanides: An Alternative Method for the StereoselectiveSynthesis of (3E)-(Imino)isoindolin-1-ones and(3E)-(Imino)thiaisoindoline 1,1-Dioxides

Bifu Liu,a Yibiao Li,a Huanfeng Jiang,a,* Meizhou Yin,a and Huawen Huanga

a School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People�sRepublic of ChinaFax: (+86)-20-8711-2906; e-mail: [email protected]

Received: March 14, 2012; Revised: May 15, 2012; Published online: August 6, 2012

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200212.

Abstract: A palladium-catalyzed, one-pot cyclizationreaction to construct (3E)-(imino)isoindolin-1-onesand (3E)-(imino)thiaisoindoline 1,1-dioxides by in-troducing ortho-reactive functional groups on arylhalides is reported. Under optimal conditions, thecyclization reaction afforded the corresponding prod-ucts in good to excellent yields (up to 93%) withhigh stereoselectivity. Notably, this transformationsuccessfully extends its application for the synthesisof phenanthridines and dibenzooxazepines. This new

synthetic protocol not only extends the applicationplatform for palladium-catalyzed C�C coupling ofaryl halides with isocyanides, but also opens atom-economic and step-economic synthetic routes for ni-trogen-containing heterocyclic compounds with widefunctional group compatibility.

Keywords: C�C coupling; isocyanides; nitrogen-con-taining heterocycles; one-pot cyclization; palladium-catalyzed reaction

Introduction

Since the pioneering work of Ugi[1] and Passerini,[2]

isocyanides have been widely applied to the creationof molecular diversity, particularly in producing struc-turally appealing nitrogen-containing heterocycles,which are low-molecular drug-like compounds andhave potential utilization in the pharmaceutical indus-try.[3] Transition metal-catalyzed reactions haveemerged as a powerful tool for the synthesis of N-containing heterocycles via the formation of carbon-carbon and carbon-heteroatom bonds and, hence,have become the most attractive methodologies inmodern organic synthesis.[4] Among a variety of tran-sition metal-catalyzed transformations, great progresshas been made in using isocyanides as precursors forthe synthesis of N-containing heterocycles. For exam-ple, Odom and co-workers[5] have reported titanium-catalyzed one-pot multicomponent coupling reactionsfor direct access to different kinds of nitrogen hetero-cycles, such as pyrazoles, pyrroles, and pyrimidines,quinolines and isoxazoles. Besides titanium catalysts,copper[6] and silver[7] have also been employed in cat-alytic cyclization reactions to prepare imidazoles, pyr-

roles and oxazolines. In addition, the transition metal-catalyzed functionalization of C�H bonds to constructuseful N-containing heterocyclics has been reported.[8]

More recently, palladium-catalyzed one-pot cycliza-tion reactions involving isocyanides have also beenapplied to the preparation of nitrogen heterocycles.[9]

Very recently, our group developed a facile methodfor the synthesis of 5-iminopyrrolones via palladium-catalyzed annulation reaction of bromoalkynes andisocyanides.[10a] Therefore, from the view point of syn-thetic chemistry, isocyanides are efficient buildingblocks for the synthesis of biologically active N-con-taining molecules and for total synthesis.

Recently, our group utilized isocyanides as a sourceof both carboxy and amino group to construct syn-thetically useful amide compounds.[10b] In this palladi-um-catalyzed C�C coupling of aryl halides with iso-cyanides, the organopalladium intermediate is pro-duced by the migratory insertion of isocyanide intothe aryl palladium intermediate, which implied thepotential possibilities of further formation of C�Cand C�N bonds. Besides, the N�H bond at an amidegroup is generally reactive, and can be further func-tionalized.[11] On the basis of the above facts, it may

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be possible to develop more convenient routes for thepreparation of N-containing heterocycles via introduc-ing reactive functional groups on suitable positions(Scheme 1).

As we know, various heterocyclic compounds con-taining the iminoisoindolinone or iminothiaisoindo-line 1,1-dioxide skeleton exhibit important pharmaco-logical activities.[12] Moreover, iminoisoindolinonesare commonly used as precursors for the synthesis ofother heterocycles.[13] However, previously reportedpathways are rare and have some drawbacks, such asusing inaccessible starting materials,[9d] low functionalgroup compatibility[14,9d] or poor stereoselectivity.[8a]

Thus, it is still necessary to develop efficient andsimple protocols to synthesize iminoisoindolinonesand their structural analogues. Herein we disclosea simple and highly efficient method for the stereose-lective synthesis of (3E)-(imino)isoindolin-1-ones and(3E)-(imino)thiaisoindoline 1,1-dioxides via Pd-cata-lyzed C�C coupling of aryl halides with isocyanides.And further exploration revealed that this catalyticsystem was also applicable for the synthesis of phe-nanthridines and dibenzooxazepines.

Results and Discussion

Palladium-Catalyzed One-Pot Cyclization Reaction ofIsocyanides with ortho-Halobenzamides

In a typical procedure, 2-bromobenzoyl chloride (1a)(0.5 mmol), aniline (2a) (0.5 mmol) and Et3N(1.0 mmol) in CH2Cl2 (2 mL) were stirred for twohours at room temperature.[15] Then the solution wasevaporated to dryness under reduced pressure. Subse-quently, solvent, tert-butyl isocyanide (3a) (0.6 mmol)and various palladium catalysts were added to screenfor the optimal reaction conditions (Table 1). Initially,we preformed this palladium-catalyzed one-pot cycli-

Scheme 1. The reaction hypothesis.

Table 1. Optimization of reaction conditions.[a]

Entry Pd source/Ligand Base Solvent Yield [%][b]

1[c] PdCl2/PPh3 CsF DMSO 322 PdCl2/PPh3 CsF DMSO 753 Pd ACHTUNGTRENNUNG(OAc)2/PPh3 CsF DMSO 574 PdBr2/PPh3 CsF DMSO 615 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 CsF DMSO 93(89)6 Pd ACHTUNGTRENNUNG(PPh3)2Cl2 CsF DMSO 507 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 – DMSO trace8 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 t-BuOK DMSO 549 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 Et3N DMSO 4710 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 K2CO3 DMSO 6911 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 Cs2CO3 DMSO 8612 Pd ACHTUNGTRENNUNG(PPh3)2Cl2 CsF DMF 7013 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 CsF toluene 3014 Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 CsF CH3CN 6515 PdCl2/PPh3 CsF 1,4-dioxane 7616[d] Pd ACHTUNGTRENNUNG(PPh3)2Cl2/PPh3 CsF DMSO 47

[a] Reactions conditions: All reactions were performed with 1a (0.5 mmol), 2a (0.5 mmol), 3a (0.6 mmol), PdX2 (5 mol%),PPh3 (10 mol%), base (2.0 equiv.), and 2.0 mL extra-dried solvent at 90 8C for 8 h unless otherwise noted.

[b] Yields and conversions analysised by GC/MS are based on 1a. Number in parentheses is isolated yield.[c] 0.2 mL of H2O was added to the extra-dried DMSO and 1.0 equiv. of CsF was used.[d] At 70 8C for 10 h.

Adv. Synth. Catal. 2012, 354, 2288 – 2300 � 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim asc.wiley-vch.de 2289

Palladium-Catalyzed C�C Coupling of Aryl Halides with Isocyanides

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zation reaction under the optimized conditions of ourprevious work.[10b] However, only a 32% yield of 4awas obtained (entry 1). Surprisingly, the yield of 4awas increased to 75% when the reaction was carriedout in extra-dried DMSO (entry 2). Testing differentpalladium catalysts (entries 3–6) found that the yieldof the desired product 4a decreased when PdCl2 wasreplaced by PdACHTUNGTRENNUNG(OAc)2 or PdBr2 (entries 3 and 4). Thebest result was obtained when Pd ACHTUNGTRENNUNG(PPh3)2Cl2 was uti-lized as the catalyst, affording 4a in 89% isolated

yield (entry 5), while the procedure was unfavorablein the absence of PPh3 (entry 6). Screening of variousbases revealed that the identity of the base was criti-cal to the success of the cyclization reaction (en-tries 7–11). Only a trace amount of 4a was detected inthe absence of base (entry 7), and we found Cs2CO3

was also effective for this reaction system (entry 11),but t-BuOK, Et3N and K2CO3 gave the product ina lower yield (entries 8–10). We next tested the cycli-zation reaction in different solvents (entries 12–15).

Table 2. Synthesis of (3E)-(imino)isoindolin-1-ones via palladium-cata-lyzed one-pot cyclization reaction.[a,b]

[a] All reactions were carried out using 1a (1.0 mmol), amines(1.0 mmol) and isocyanides (1.2 mmol), Pd ACHTUNGTRENNUNG(PPh3)2Cl2 (5 mol%),PPh3 (10 mol%), CsF (2.0 equiv.) in 2.0 mL extra-dried DMSO at90 8C for 8 h unless otherwise noted.

[b] Isolated yield.[c] 93% isolated yield was obtained at 70 8C for 8 h when 1a was re-

placed by 2-iodobenzoyl chloride.[d] The isocyanide 4q is (isocyanomethyl)trimethylsilane.

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Comparing with DMSO, the yields of 4a were muchlower when DMF, CH3CN, or 1,4-dioxane were usedas the solvents (entries 12, 14, and 15). Notably, thereaction was sluggish when toluene was employed(entry 13). Lower temperature disfavored the reactionand only gave a 47% yield of 4a after 10 h (entry 16).

With the optimized reaction conditions in hand,various amines and isocyanides were employed in thistransformation to investigate the reaction’s scope andlimitations (Table 2). In all of the examples investigat-ed, good to excellent yields of the correspondingproducts were obtained, which indicates the excep-tional generality of this novel methodology. Asa matter of fact, both aromatic (4a–4i) and alkyl (4j–4n) amines[16] exclusively gave the (3E)-(imino)isoin-dolin-1-ones in good to excellent yields. Generally,the aromatic rings with electron-donating groups (4b–4d) afforded higher yields of the products than thatwith electron-withdrawing groups (4e–4i). It wasfound that steric hindrance has a slight effect on thereaction (4e–4g). Meanwhile, good yields wereachieved when alkyl- (4j–4l), cyclohexyl- (4m) andbenzyl- (4n) amines were used, although the yields ofthe desired product were slightly lower than with cor-responding aromatic amines. Various alkyl, cycloalkyl,and aryl isocyanides (4o–4u) were also employed toprobe the scope of the reaction substrates. Almost allthe isocyanides were found suitable for this transfor-mation, affording the corresponding (3E)-(imino)-ACHTUNGTRENNUNGisoindolin-1-ones in good yields. Even if stericallybulky isocyanides such as 1,1,3,3-tetramethylbutyl iso-cyanide and 2,6-dimethylphenyl isocyanide were used,the reaction afforded the corresponding 4o and 4t in92% and 81% yield, respectively. Interestingly, 4q wasobtained in 78% yield when (isocyanomethyl)trime-thylsilane was used, caused by the cleavage of the tri-methylsilyl group. In addition to the secondary, terti-ary, and aromatic isocyanides, primary isocyanideswere also effective in affording the corresponding(3E)-(imino)isoindolin-1-ones with excellent stereose-

lectivity and in good yields (4v, 4w). We also extendedthis transformation to 2-iodobenzoyl chloride (1a’)and found that the cyclization reaction gave an evenbetter yield than with 1a at a lower reaction tempera-ture (4a). In order to confirm the structure of theproducts obtained, the molecular structure of com-pound 4e was established by X-ray crystallography(Figure 1).[17]

Palladium-Catalyzed One-Pot Cyclization Reaction ofIsocyanides with ortho-Halobenzenesulfonamides

To further demonstrate the synthetic potential of ourmethodology, we used 2-bromobenzene-1-sulfonyl(1b), amines (2) and isocyanides as substrates underthe same reaction conditions to gain the correspond-ing (3E)-(imino)-thiaisoindoline 1,1-dioxides (5). Toexplore the scope and limitations of this reaction, weextended the procedure to various amines and isocya-nides (Table 3). To our delight, both aromatic (5a–5d)and aliphatic (5e–5h) amines have been successfullyconverted to the desired products in good to excellentyields (70–87%) under the optimized conditions. Tostudy the effects of the electronic properties of sub-stituents on aromatic amines, both electron-donating(5b) and electron-withdrawing groups (5c, 5d) on thearomatic ring were screened. These results showedthat the electronic properties of the aromatic amineshad no obvious effect on the yield of the desiredproducts. Besides, the result of the experimentshowed that when methanamine and tert-butylaminewere used, the corresponding products were obtainedin 78% (5e) and 70% (5f) yields respectively, whichwere much lower than those of propylamine (5g) andisopropylamine (5h). In addition, cyclohexanamineand phenylmethanamine also reacted to form theproducts 5i and 5j in high yields.

Finally, the scope of the process with respect toa variety of isocyanides was examined (5k–5q). Reac-tion of isopropyl isocyanide (5k) was more efficientthan those of tert-butylisonitrile as reflected by thefact that the corresponding (3E)-(imino)-thiaisoindo-line 1,1-dioxide was formed in a much higher yield(88%). It was worthy to note that the steric hindranceon isocyanides had a great influenence on the one-potcyclization reaction. As shown in Table 3, when1,1,3,3-tetramethylbutyl isocyanide (5l) was used inthis process, no desired product was detected. A simi-lar phenomenon occurred when sterically hinderedaryl isocyanides were used, such as 2,6-dimethylphen-yl isocyanide when only 47% yield of the correspond-ing product (5p) obtained. However, the less hinderedp-methoxyphenyl isonitrile (5q) successfully partici-pated in this process, giving the desired product in ex-cellent yield (85%). Moreover, primary isocyanides(5m, 5n) and cyclohexyl isocyanide (5o) were also ef-Figure 1. X-ray structure of compound 4e.




fective to afford the corresponding (3E)-(imino)thia-ACHTUNGTRENNUNGisoindoline 1,1-dioxides in good yields.

Synthesis of Phenanthridines and Dibenzooxazepines

With these results in hand, we envisioned that the 2’-bromobiaryl-2-amines can also be applied to thistransformation (Scheme 2). Not surprisingly, (E)-1-[6-(tert-butylimino)phenanthridin-5(6H)-yl]ethanone

(8a) and (E)-[6-(tert-butylimino)phenanthridin-5(6H)-yl]ACHTUNGTRENNUNG(phenyl)methanone (8b) were obtained corre-spondingly when the free amino group of the 2’-bro-mobiaryl-2-amines was protected by an acetyl or ben-zoyl group. To our surprise, N-(tert-butyl)phenanthri-din-6-amine (9a) and N-(tert-butyl)dibenzo ACHTUNGTRENNUNG[b,f]-ACHTUNGTRENNUNG[1,4]oxazepin-11-amine (10a) were obtained in excel-lent yields when 2’-bromo-[1,1’-biphenyl]-2-amine(6a) and 2-(2-bromophenoxy)aniline (6b) were usedas substrates under the standard reaction conditions.

Table 3. Synthesis of (3E)-(imino)thiaisoindoline 1,1-dioxides via palladium-cata-lyzed one-pot cyclization reaction.[a,b]

[a] All reactions were carried out using 1b (1.0 mmol), amines (1.0 mmol) and 3a(1.2 mmol), Pd ACHTUNGTRENNUNG(PPh3)2Cl2 (5 mol%), PPh3 (10 mol%), CsF (2.0 equiv.) in2.0 mL extra-dried DMSO at 90 8C for 8 h unless otherwise noted.

[b] Isolated yield.[c] 90% isolated yield was obtained at 70 8C for 8 h when 1b was replaced by 2-io-

dobenzene-1-sulfonyl chloride.




It is noteworthy that phenanthridines and dibenzoox-azepins are important units in numerous biologicallyactive natural products and medicinally significantcompounds.[18] We presume that the intermediates (9’and 10’) were unstable and easily tautomerized[8c,18c]

to the corresponding 6-aminophenanthridines (9) and11-aminodibenzooxazepines (10). Next, we examinedother isocyanides under the standard reaction condi-tions. Specifically, alkyl, cycloalkyl, and aryl isocya-nides were employed to probe the scope of the sub-strates. As shown in Scheme 2, almost all the isocya-nides were found suitable for this transformation, af-fording the corresponding 6-aminophenanthridines(9b–9d) and 11-aminodibenzooxazepines (10b and10c) in high yield. These examples demonstrate thegreat potential of our new method for the construc-tion pharmacologically interesting nitrogen heterocy-cles.

Plausible Reaction Mechanism

Based on the previous palladium-catalyzed C�C cou-pling of aryl halides with isocyanides,[10] a plausiblemechanism of this one-pot cyclization reaction wasproposed (Scheme 3). Initial oxidative addition ofortho-halobenzamides or ortho-halobenzenesulfon-ACHTUNGTRENNUNGamides (A) to a zerovalent Pd species affords aryl

palladium intermediate B. Subsequent insertion ofisocyanide into the palladium-carbon bond results inthe intermediate C. With the aid of the base, hydro-gen halide was extruded out of C to generate the six-membered ring azapalladacyclic intermediate D. Fi-nally, reductive elimination affords E, regeneratingthe palladium(0) catalyst.

Conclusions

In summary, we have demonstrated a most efficient,mild, concise and facile protocol for the synthesis ofsubstituted (3E)-(imino)isoindolin-1-ones and (3E)-(imino)thiaisoindoline 1,1-dioxides via a palladium-catalyzed one-pot cyclization reaction. Good to excel-lent yields and high stereoselectivity of the targetproducts were generally obtained from a broad rangeof substrates. More importantly, this transformationwas successfully applied to the synthesis of phenan-thridines and dibenzooxazepines. In addition, all ofthe starting materials for the palladium-catalyzedone-pot cyclization reaction were commercially avail-able and the reactions were easy to handle, which of-fered a simple way to increase the product diversityand structural complexity. Further research on thepreparation of other useful nitrogen heterocycles bythis catalytic system is underway in our laboratory.

Scheme 2. Palladium-catalyzed synthesis of phenanthridines and dibenzooxazepines.




Experimental Section

General Methods

All reactions were carried out in 10-mL tubes. TLC was per-formed by using commercially prepared 100–400 mesh silicagel plates (GF254) and visualization was effected at 254 nm.The starting materials 6a and 6b were prepared according tothe literature.[19] Other reagents were purchased as reagentgrade and used without further purification. Extra-driedDMSO was purchased as reagent grade and used withoutfurther dehydration. Melting points were measured witha B�chi B-545 melting point instrument and are uncorrect-ed. 1H and 13C NMR spectra were recorded on a 400 MHzspectrometer using CDCl3 as solvent and TMS as an internalstandard. The chemical shifts were referenced to signals at7.24 and 77.0 ppm, respectively.

General Procedure for the Synthesis of (3E)-(Imino)-isoindolin-1-ones and (3E)-(Imino)thiaisoindoline1,1-Dioxides

2-Bromobenzoyl chloride (1a) (1.0 mmol) or 2-bromobenze-nesulfonyl chloride (1b) (1.0 mmol), aniline (2a) (1.0 mmol)and Et3N (2.0 mmol) in CH2Cl2 (2 mL) were stirred for twohours at room temperature. Then the solution was evaporat-ed to dryness under reduced pressure. Subsequently,Pd ACHTUNGTRENNUNG(PPh3)2Cl2 (5 mol%), PPh3 (10 mol%), CsF (2.0 equiv.)and extra-dried DMSO (2 mL) were added and the mixturewas stirred for five minutes at room temperature, then the

isocyanide (1.2 mmol) was added, and the mixture wasstirred at 90 8C for 12 h in 10-mL sealed tubes. Monitoringwith TLC was used to show when the reaction was com-plete. Upon completion, the reaction mixture was extractedwith ethyl acetate (3 � 10 mL), and the combined organicphase was dried with anhydrous MgSO4 and concentratedunder vacuum. The residue was loaded on a silica columnand purified by column chromatography (petroleum ether/ethyl acetate, 10:1) to give the final product. The stereo-chemistry was confirmed by the X-ray diffraction, see Sup-porting Information.

General Procedure for the Synthesis of Phenan-thridines and Dibenzooxazepines

To the mixture of 6a or 6b (1.0 mmol), Pd ACHTUNGTRENNUNG(PPh3)2Cl2

(5 mol%), PPh3 (10 mol%) in extra-dried DMSO (2 mL),CsF (2.0 equiv.) were added successively and stirred for fiveminutes at the room temperature. Then the isocyanide(1.2 mmol) was added and the mixture was stirred at 90 8Cfor 12 h in 10-mL sealed tubes. Monitoring with TLC wasused to show when the reaction was complete. Upon com-pletion, the reaction mixture was extracted with ethyl ace-tate (3 � 10 mL), and the combined organic phase was driedwith anhydrous MgSO4 and concentrated under vacuum.The residue was loaded on silica column and purified bycolumn chromatography (petroleum ether/ethyl acetate,10:1) to give the final product.

(E)-3-(tert-Butylimino)-2-phenylisoindolin-1-one (4a):Light yellow solid; mp 120–122 8C; IR (KBr): n=2969, 2362,

Scheme 3. Proposed mechanism for the one-pot cyclization reaction.




1729, 1660, 1371, 1140, 698 cm�1; 1H NMR (400 MHz,CDCl3): d= 8.07 (d, J= 7.6 Hz, 1 H), 7.98 (d, J=7.2 Hz, 1 H),7.71–7.61 (m, 2 H), 7.45–7.38 (m, 4 H), 7.33–7.29 (m, 1 H),1.49 (s, 9 H); 13C NMR (100 MHz, CDCl3): d= 166.6, 146.7,134.3, 133.6, 132.3, 131.2, 128.5, 128.5, 128.0, 127.2, 126.8,123.5, 53.8, 30.5; ESI-HR-MS: m/z =279.1489, calcd. forC18H18N2O (M+ H)+: 279.1492.

(E)-3-(tert-Butylimino)-2-(4-methoxyphenyl)isoindolin-1-one (4b): Light yellow solid; mp 136–138 8C; IR (KBr): n=2967, 2360, 1725, 1659, 1512, 1377, 1246, 1143, 1030,703 cm�1; 1H NMR (400 MHz, CDCl3): d=8.04 (d, J=7.6 Hz, 1 H), 7.95 (d, J=7.2 Hz, 1 H), 7.68–7.58 (m, 2 H),7.30–7.26 (m, 2 H), 6.97–6.93 (m, 2 H), 3.80 (s, 3 H), 1.47 (s,9 H); 13C NMR (100 MHz, CDCl3); d=166.8, 158.1, 146.9,133.6, 132.2, 131.1, 129.5, 128.6, 127.1, 127.0, 123.4, 113.4,55.2, 53.8, 30.5; ESI-HR-MS: m/z=309.1593, calcd. forC19H20N2O2 (M +H)+: 309.1598.

(E)-3-(tert-Butylimino)-2-(3,4-dimethylphenyl)isoindolin-1-one (4c): Light yellow solid; mp 124–126 8C; IR (KBr):n=2966, 2359, 1727, 1660, 1505, 1371, 1140, 702 cm�1;1H NMR (400 MHz, CDCl3): d=8.06 (d, J= 7.6 Hz, 1 H),7.98 (d, J=7.2 Hz, 1 H), 7.70–7.60 (m, 2 H), 7.20–7.09 (m,3 H), 2.28 (s, 6 H), 1.49 (s, 9 H); 13C NMR (100 MHz,CDCl3): d=166.9, 146.9, 136.3, 135.3, 133.7, 132.2, 131.9,131.1, 129.4, 129.3, 128.7, 127.2, 125.8, 123.5, 53.9, 30.6, 19.8,19.4; ESI-HR-MS: m/z =307.1801, calcd. for C20H22N2O(M+ H)+: 307.1805.

(E)-3-(tert-Butylimino)-2-(4-phenoxyphenyl)isoindolin-1-one (4d): Light yellow solid; mp 140–142 8C; IR (KBr): n=2967, 2359, 1726, 1658, 1500, 1370, 1234, 1140, 698 cm�1;1H NMR (400 MHz, CDCl3): d=8.07 (d, J= 7.6 Hz, 1 H),7.98 (d, J=7.6 Hz, 1 H), 7.71–7.62 (m, 2 H), 7.36–7.32 (m,4 H), 7.12–7.04 (m, 5 H), 1.50 (s, 9 H); 13C NMR (100 MHz,CDCl3): d=166.8, 156.8, 155.9, 146.8, 133.6, 132.3, 131.2,129.8, 129.7, 129.3, 128.6, 127.2, 123.6, 123.4, 119.2, 118.0,53.9, 30.6; ESI-HR-MS: m/z =371.1747, calcd. forC24H22N2O2 (M +H)+: 371.1754.

(E)-3-(tert-Butylimino)-2-(2-chlorophenyl)isoindolin-1-one (4e): White solid; mp 139–141 8C; IR (KBr): n= 2966,2357, 1730, 1659, 1479, 1367, 1147, 701 cm�1; 1H NMR(400 MHz, CDCl3): d=8.06 (d, J= 7.6 Hz, 1 H), 7.98 (d, J=7.6 Hz, 1 H), 7.69 (t, J=7.4 Hz, 1 H), 7.62 (t, J= 7.4 Hz, 1 H),7.48–7.46 (m, 1 H), 7.35–7.28 (m, 3 H), 1.42 (s, 9 H);13C NMR (100 MHz, CDCl3): d=166.2, 145.8, 133.6, 133.5,132.8, 132.4, 131.4, 131.1, 129.6, 129.2, 128.9, 127.1, 126.9,123.7, 53.8, 30.4; ESI-HR-MS: m/z =313.1095, calcd. forC18H17ClN2O (M+ H)+: 313.1102.

(E)-3-(tert-Butylimino)-2-(3-chlorophenyl)isoindolin-1-one (4f): Light yellow solid; mp 158–160 8C; IR (KBr): n=2969, 2357, 1726, 1660, 1472, 1361, 684 cm�1; 1H NMR(400 MHz, CDCl3): d=8.06 (d, J= 7.6 Hz, 1 H), 7.98 (d, J=7.6 Hz, 1 H), 7.73–7.63 (m, 2 H), 7.42 (t, J= 1.8 Hz, 1 H),7.37–7.26 (m, 3 H), 1.49 (s, 9 H); 13C NMR (100 MHz,CDCl3): d=166.4, 146.3, 135.4, 133.4, 132.6, 131.4, 129.0,128.8, 128.5, 127.4, 127.0, 126.7, 123.8, 54.1, 30.5; ESI-HR-MS: m/z =313.1093. calcd. for C18H17ClN2O (M +H)+:313.1102.

(E)-3-(tert-Butylimino)-2-(4-chlorophenyl)isoindolin-1-one (4g): White solid; mp 152–154 8C; IR (KBr): n= 2966,2380, 1729, 1660, 1492, 1373, 1138, 1087, 701 cm�1; 1H NMR(400 MHz, CDCl3): d=8.06 (d, J= 7.6 Hz, 1 H), 7.96 (d, J=7.6 Hz, 1 H), 7.69 (t, J=7.6 Hz, 1 H), 7.62 (t, J= 7.4 Hz, 1 H),

7.39–7.32 (m, 4 H), 1.48 (s, 9 H); 13C NMR (100 MHz,CDCl3): d=166.4, 146.4, 133.4, 132.8, 132.5, 132.3, 131.3,129.7, 128.4, 128.1, 127.3, 123.6, 53.9, 30.5; ESI-HR-MS:m/z= 313.1098, calcd. for C18H17ClN2O (M +H)+: 313.1102.

(E)-3-(tert-Butylimino)-2-(3,4-dichlorophenyl)isoindolin-1-one (4h): White solid; mp 132–134 8C; mp 134–136 8C; IR(KBr): n=2970, 2361, 1731, 1665, 1475, 1369, 1135,701 cm�1; 1H NMR (400 MHz, CDCl3): d=8.06 (d, J=8.0 Hz, 1 H), 7.94 (d, J=7.2 Hz, 1 H), 7.72–7.68 (m, 1 H),7.64–7.61 (m, 1 H), 7.55(d, J=2.4 Hz, 1 H), 7.45 (d, J=8.4 Hz, 1 H), 7.28 (dd, J1 =J2 = 2.4 Hz, 1 H), 1.48 (s, 9 H);13C NMR (100 MHz, CDCl3): d=166.1, 146.0, 133.6, 133.1,132.7, 131.6, 131.5, 130.5, 130.3, 129.5, 128.3, 127.7, 127.4,123.7, 54.0, 30.4; ESI-HR-MS: m/z =347.0705, calcd. forC18H16Cl2N2O (M +H)+: 347.0712.

(E)-3-(tert-Butylimino)-2-(4-fluorophenyl)isoindolin-1-one(4i): Light yellow solid; mp 131–133 8C; IR (KBr): n= 2969,2360, 1722, 1656, 1508, 1368, 1224, 1143, 701 cm�1; 1H NMR(400 MHz, CDCl3): d=8.06 (d, J= 7.6 Hz, 1 H), 7.96 (d, J=7.6 Hz, 1 H), 7.71–7.61 (m, 2 H), 7.37–7.31 (m, 2 H), 7.13–7.07 (m, 2 H), 1.48 (s, 9 H); 13C NMR (100 MHz, CDCl3):d= 166.7, 162.4, 160.0, 146.7, 133.5, 132.4, 131.3, 130.1 (d, J=8.5 Hz), 128.5, 127.3, 123.6, 114.9 (d, J=22.5 Hz), 53.9, 30.5;ESI-HR-MS: m/z= 297.1392, calcd. for C18H17FN2O (M+H)+: 297.1398.

(E)-3-(tert-Butylimino)-2-methylisoindolin-1-one (4j):Light yellow solid; mp 132–135 8C; IR (KBr): n=2925, 2360,1724, 1645, 1515, 1463, 1423, 1364, 694 cm�1; 1H NMR(400 MHz, CDCl3): d=7.94 (d, J= 7.6 Hz, 1 H), 7.84 (d, J=7.6 Hz, 1 H), 7.60–7.51 (m, 2 H), 3.13 (s, 3 H), 1.50 (s, 9 H);13C NMR (100 MHz, CDCl3): d=167.4, 147.3, 134.3, 131.7,130.8, 129.0, 127.0, 123.0, 53.6, 30.7, 25.1; ESI-HR-MS:m/z= 217.1329, calcd. for C13H16N2O (M +H)+: 217.1335.

(E)-3-(tert-Butylimino)-2-hexylisoindolin-1-one (4k):Yellow oil; IR (KBr): n=2928, 2359, 1721, 1651, 1512, 1394,702 cm�1; 1H NMR (400 MHz, CDCl3): d=7.94 (d, J=7.6 Hz, 1 H), 7.84 (d, J=7.2 Hz, 1 H), 7.60–7.51 (m, 2 H),3.71 (t, J=7.2 Hz, 2 H), 1.61–1.55 (m, 2 H), 1.50 (s, 9 H),1.34–1.21 (m, 6 H), 0.83 (t, J=6.8 Hz, 3 H); 13C NMR(100 MHz, CDCl3): d= 167.2, 146.4, 134.3, 131.6, 130.8,128.8, 126.9, 123.0, 53.6, 38.3, 31.4, 30.7, 28.1, 26.6, 22.5,14.0; ESI-HR-MS: m/z =287.2112, calcd. for C18H26N2O(M+ H)+: 287.2118.

(E)-2-Butyl-3-(tert-butylimino)isoindolin-1-one (4l): Lightyellow oil; IR (KBr): n= 2927, 2356, 1694, 1649, 1517,670 cm�1; 1H NMR (400 MHz, CDCl3): d=7.95 (d, J=7.6 Hz, 1 H), 7.86 (d, J=6.4 Hz, 1 H), 7.61–7.53 (m, 2 H),3.74 (t, J=7.2 Hz, 2 H), 1.63–1.55 (m, 2 H), 1.52 (s, 9 H),1.36–1.29 (m, 2 H), 0.91 (t, J=7.2 Hz, 3 H); 13C NMR(100 MHz, CDCl3): d= 167.3, 146.5, 134.4, 131.7, 130.8,128.9, 127.0, 123.1, 53.6, 38.1, 30.8, 30.4, 20.1, 13.4; ESI-HR-MS: m/z =259.1801, calcd. for C16H22N2O (M +H)+:259.1805.

(E)-3-(tert-Butylimino)-2-cyclohexylisoindolin-1-one(4m): Light yellow solid; mp 67–69 8C; IR (KBr): n= 2927,2359, 1713, 1652, 1515, 1363, 704 cm�1; 1H NMR (400 MHz,CDCl3): d= 7.93 (d, J= 7.6 Hz, 1 H), 7.82 (d, J=6.4 Hz, 1 H),7.59–7.51 (m, 2 H), 4.36–4.28 (m, 1 H), 2.40–2.30 (m, 2 H),1.85–1.75 (m, 2 H), 1.65–1.59 (m, 2 H), 1.52 (s, 9 H), 1.37–1.16 (m, 4 H); 13C NMR (100 MHz, CDCl3): d=167.3, 146.2,134.5, 131.5, 130.7, 128.4, 126.9, 122.9, 53.7, 50.1, 30.8, 29.4,




26.4, 25.5; ESI-HR-MS: m/z =285.1952, calcd. forC18H24N2O (M+ H)+: 285.1961.

(E)-2-Benzyl-3-(tert-butylimino)isoindolin-1-one (4n):White solid; mp 107–109 8C; IR (KBr): n= 2964, 2359, 1717,1653, 1516, 1396, 701 cm�1; 1H NMR (400 MHz, CDCl3): d=7.96 (d, J=7.6 Hz, 1 H), 7.88 (d, J= 7.2 Hz, 1 H), 7.61–7.52(m, 2 H), 7.46 (d, J= 7.6 Hz, 2 H), 7.28–7.17 (m, 3 H), 4.94 (s,2 H), 1.52 (s, 9 H); 13C NMR (100 MHz, CDCl3): d= 167.0,146.0, 138.2, 134.1, 131.9, 130.9, 128.9, 128.8, 128.0, 127.0,126.9, 123.2, 53.7, 41.8, 30.7; ESI-HR-MS: m/z= 293.1646,calcd. for C19H20N2O (M +H)+: 293.1648.

(E)-2-(4-Chlorophenyl)-3-[(2,4,4-trimethylpentan-2-yl)-imino]isoindolin-1-one (4o): Yellow oil; IR (KBr): n= 2950,2360, 1728, 1660, 1493, 1373, 1087, 701 cm�1; 1H NMR(400 MHz, CDCl3): d=8.08 (d, J= 7.6 Hz, 1 H), 7.95 (d, J=7.2 Hz, 1 H), 7.70–7.60 (m, 2 H), 7.38–7.35 (m, 2 H), 7.27–7.24 (m, 2 H), 1.79 (s, 2 H), 1.50 (s, 6 H), 0.81 (s, 9 H);13C NMR (100 MHz, CDCl3): d=166.5, 145.5, 133.7, 133.2,132.8, 132.4, 131.2, 130.2, 128.7, 128.3, 127.1, 123.6, 57.9,56.0, 31.7, 31.6, 30.1; ESI-HR-MS: m/z= 369.1724, calcd. forC22H25ClN2O (M+ H)+: 369.1728.

(E)-2-(4-Chlorophenyl)-3-(isopropylimino)isoindolin-1-one (4p): Light yellow solid; mp 91–93 8C; IR (KBr): n=2970, 2359, 1731, 1664, 1494, 1375, 1117, 699 cm�1; 1H NMR(400 MHz, CDCl3): d=7.99–7.93 (m, 2 H), 7.68–7.60 (m,2 H), 7.44–7.38 (m, 4 H), 4.68–4.59 (m, 1 H), 1.29 (s, 6 H);13C NMR (100 MHz, CDCl3): d=166.4, 148.3, 133.3, 132.5,132.2, 132.2, 131.5, 129.3, 129.1, 128.4, 125.7, 123.7, 49.6,24.1; ESI-HR-MS: m/z= 299.0942, calcd. for C17H15ClN2O(M+ H)+: 299.0946.

(E)-2-(4-Chlorophenyl)-3-(methylimino)isoindolin-1-one(4q): Yellow solid; mp 139–141 8C; IR (KBr): n=2925, 2360,1735, 1660, 1382, 1031, 695 cm�1; 1H NMR (400 MHz,CDCl3): d= 7.82 (d, J= 7.6 Hz, 1 H), 7.53–7.49 (m, 1 H),7.32–7.29 (m, 3 H), 6.91–6.89 (m, 2 H), 6.68 (d, J= 8.0 Hz,1 H), 3.31 (s, 3 H); 13C NMR (100 MHz, CDCl3): d= 167.6,151.8, 147.3, 132.7, 132.5, 132.0, 129.5, 129.4, 125.2, 123.4,121.3, 25.2; ESI-HR-MS: m/z =271.0626, calcd. forC15H11ClN2O (M+ H)+: 271.0633.

(E)-2-(4-Chlorophenyl)-3-(cyclohexylimino)isoindolin-1-one (4r): Yellow solid; mp 149–151 8C; IR (KBr): n= 2929,2362, 1732, 1662, 1494, 1378, 1090, 697 cm�1; 1H NMR(400 MHz, CDCl3): d=7.97 (d, J= 7.2 Hz, 1 H), 7.92 (d, J=7.6 Hz, 1 H), 7.72–7.63 (m, 2 H), 7.41–7.36 (m, 4 H), 4.31–4.23 (m, 1 H), 1.87–1.78 (m, 4 H), 1.67–1.64 (m, 1 H), 1.59–1.49 (m, 2 H), 1.47–1.37 (m, 2 H), 1.33–1.24 (m, 1 H);13C NMR (100 MHz, CDCl3): d=166.6, 148.4, 133.4, 132.6,132.4, 132.4, 131.6, 129.3, 128.5, 125.6, 123.9, 57.6, 34.1, 25.5,24.4; ESI-HR-MS: m/z =339.1250, calcd. for C20H19ClN2O(M+ H)+: 339.1259.

(E)-2-(4-Chlorophenyl)-3-(cyclopentylimino)isoindolin-1-one (4s): White solid; mp 128–130 8C; IR (KBr): n= 2954,2360, 1731, 1662, 1493, 1377, 1089, 699 cm�1; 1H NMR(400 MHz, CDCl3): d=8. 02(d, J=7.6 Hz, 1 H), 7.95 (d, J=6.8 Hz, 1 H), 7.69–7.60 (m, 2 H), 7.42–7.34 (m, 4 H), 4.80–4.74 (m, 1 H), 2.03–1.94 (m, 2 H), 1.83–1.74 (m, 2 H), 1.73–1.61 (m, 4 H); 13C NMR (100 MHz, CDCl3): d=166.4, 148.7,133.2, 132.4, 132.3, 132.2, 131.5, 129.2, 129.1, 128.3, 125.6,123.7, 59.9, 35.1, 24.2; ESI-HR-MS: m/z= 325.1097, calcd.for C19H17ClN2O (M +H)+: 325.1102.

(E)-2-(4-Chlorophenyl)-3-[(2,6-dimethylphenyl)imino]-isoindolin-1-one (4t):[9d] Yellow solid; mp 136–138 8C; IR

(KBr): n=2920, 2359, 1741, 1671, 1493, 1379, 1087, 771,701 cm�1; 1H NMR (400 MHz, CDCl3): d=7.93 (d, J=7.6 Hz, 1 H), 7.59 (t, J= 7.6 Hz, 1 H), 7.54–7.49 (m, 4 H), 7.39(t, J=7.6 Hz, 1 H), 7.10–6.99 (m, 3 H), 6.61 (d, J= 7.6 Hz,1 H), 2.05 (s, 6 H); 13C NMR (100 MHz, CDCl3): d= 166.8,150.8, 145.7, 133.9, 133.6, 132.5, 131.8, 131.3, 129.7, 129.2,129.1, 128.2, 126.3, 124.3, 123.8, 123.7, 18.1; MS (EI): m/z=77, 102, 130, 151, 179, 219, 234, 255, 281, 315, 345, 360.

(E)-2-(4-Chlorophenyl)-3-[(4-methoxyphenyl)imino]isoin-dolin-1-one (4u): Yellow solid; mp 56–58 8C; IR (KBr): n=2929, 2362, 1736, 1658, 1498, 1382, 1239,1117, 697 cm�1;1H NMR (400 MHz, CDCl3): d=7.93 (d, J= 7.6 Hz, 1 H),7.58 (t, J=7.6 Hz, 1 H), 7.49–7.44 (m, 4 H), 7.38 (t, J=7.6 Hz, 1 H), 6.93–6.86 (m, 4 H), 6.79 (d, J= 7.6 Hz, 1 H),3.83 (s, 3 H); 13C NMR (100 MHz, CDCl3): d= 166.9, 156.7,151.4, 141.5, 133.6, 133.1, 132.2, 131.9, 131.8, 129.2, 129.2,129.1, 125.8, 123.8, 120.6, 114.6, 55.5; ESI-HR-MS: m/z=363.0908, calcd. for C21H16ClN2O2 (M+H)+: 363.0895.

(E)-3-(Butylimino)-2-(4-chlorophenyl)isoindolin-1-one(4v): Pale yellow oily liquid; IR (KBr): n=2958, 2353, 1700,1625, 1520, 593 cm�1; 1H NMR (400 MHz, CDCl3): d= 7.82(d, J=7.2 Hz, 1 H), 7.51 (t, J= 7.4 Hz, 1 H), 7.35–7.29 (m,3 H), 6.90–6.88 (m, 2 H), 6.68 (d, J=7.6 Hz, 1 H), 3.85 (t, J=7.2 Hz, 2 H), 1.76–1.68 (m, 2 H), 1.44–1.35 (m, 2 H), 0.95 (t,J=7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d= 167.7,151.3, 147.4, 132.7, 132.5, 132.0, 129.5, 129.4, 129.4, 125.2,123.4, 121.3, 38.7, 30.4, 20.2, 13.8; ESI-HR-MS: m/z =313.1108, calcd. for C18H18ClN2O (M +H)+: 313.1102.

(E)-2-(4-Chlorophenyl)-3-[(2-morpholinoethyl)imino]iso-indolin-1-one (4w): Yellow solid; mp 65–67 8C; IR (KBr):n=2935, 2345, 1736, 1658, 1479, 1412, 1232,1107, 721 cm�1;1H NMR (400 MHz, CDCl3): d=7.83 (d, J= 7.2 Hz, 1 H),7.53 (t, J=7.6 Hz, 1 H), 7.35–7.31 (m, 3 H), 6.88 (d, J=8.0 Hz, 2 H), 6.69 (d, J=7.6 Hz, 1 H), 4.00 (t, J= 6.4 Hz,2 H), 3.73–3.60 (m, 4 H), 2.77–2.68 (m, 2 H), 2.65–2.47 (m,4 H); 13C NMR (100 MHz, CDCl3): d=167.6, 164.7, 151.2,147.3, 132.1, 132.0, 129.4, 128.5, 128.4, 125.2, 123.4, 121.2,66.9, 56.1, 53.6, 53.4; ESI-HR-MS: m/z= 370.1313, calcd. forC20H21ClN3O2 (M +H)+: 370.1317.

(E)-3-(tert-Butylimino)-2-phenyl-2,3-dihydrobenzo[d]iso-thiazole 1,1-dioxide (5a): White solid; mp 164–166 8C; IR(KBr): n=2926, 2360, 1659, 1319, 1236, 1188, 1128, 973,772 cm�1; 1H NMR (400 MHz, CDCl3): d=7.76 (d, J=7.6 Hz, 1 H), 7.53 (t, J=7.6 Hz, 1 H), 7.34 (t, J= 7.8 Hz, 2 H),7.24 (t, J=8.2 Hz, 1 H), 7.12 (t, J=7.4 Hz, 1 H), 6.83 (d, J=7.2 Hz, 2 H), 6.68 (d, J=8.0 Hz, 1 H), 1.85 (s, 9 H); 13C NMR(100 MHz, CDCl3): d= 148.3, 143.3, 137.3, 132.5, 132.1,129.7, 126.8, 124.5, 123.4, 120.6, 118.9, 60.9, 27.8; ESI-HR-MS: m/z=315.1169, calcd. for C17H18N2O2S (M+ H)+:315.1162.

(E)-3-(tert-Butylimino)-2-(4-methoxyphenyl)-2,3-dihydro-benzo[d]isothiazole 1,1-dioxide (5b): Yellow solid; mp 122–124 8C; IR (KBr): n=2928, 2358, 1661, 1489, 1315, 1237,1192, 979, 766 cm�1; 1H NMR (400 MHz, CDCl3): d=7.77(d, J=7.6 Hz, 1 H), 7.54 (t, J=7.6 Hz, 1 H), 7.28 (t, J=7.8 Hz, 1 H), 6.91 (d, J=8.0 Hz, 2 H), 6.76 (d, J= 7.6 Hz,3 H), 3.82 (s,3 H), 1.85 (s, 9 H); 13C NMR (100 MHz, CDCl3):d= 156.1, 144.0, 141.7, 137.4, 132.6, 132.1, 126.9, 124.5, 120.6,119.9, 115.0, 60.9, 27.8; ESI-HR-MS: m/z= 345.1273, calcd.for C18H20N2O3S (M+ H)+ 345.1267.

(E)-3-(tert-Butylimino)-2-(4-chlorophenyl)-2,3-dihydro-benzo[d]isothiazole 1,1-dioxide (5c): Light yellow solid; mp




173–175 8C; IR (KBr): n=2926, 2360, 1660, 1320, 1236,1186, 1129, 974, 834, 652 cm�1; 1H NMR (400 MHz, CDCl3);d= 7.77 (d, J=7.6 Hz, 1 H), 7.57 (t, J=7.6 Hz, 1 H), 7.34–7.29 (m, 3 H), 6.79–6.77 (m, 3 H), 1.83 (s, 9 H); 13C NMR(100 MHz, CDCl3): d= 146.8, 143.7, 137.3, 132.6, 132.4,129.6, 128.5, 126.6, 124.2, 120.7, 120.3, 61.0, 27.7; ESI-HR-MS: m/z =371.0622, calcd. for C17H17ClN2O2S (M+Na)+:371.0591.

(E)-3-(tert-Butylimino)-2-(4-fluorophenyl)-2,3-dihydro-benzo[d]isothiazole 1,1-dioxide (5d): Yellow solid; mp 138–140 8C; IR (KBr): n=2977, 2360, 1660, 1501, 1319, 1193,1131, 976, 839 cm�1; 1H NMR (400 MHz, CDCl3): d=7.76(d, J=7.6 Hz, 1 H), 7.56 (t, J=7.4 Hz, 1 H), 7.30 (t, J=7.8 Hz, 1 H), 7.04 (t, J= 8.0 Hz, 2 H), 6.80–6.77 (m, 2 H), 6.73(d, J=8.0 Hz, 1 H), 1.83 (s, 9 H); 13C NMR (100 MHz,CDCl3): d=160.4, 158.0, 144.3 (d, J=2.7 Hz), 144.0, 137.3,132.4 (d, J=27.5 Hz), 126.6, 124.2, 120.6, 120.1 (d, J=7.7 Hz), 116.3 (d, J= 22.3 Hz), 60.9, 27.7; ESI-HR-MS:m/z= 333.1084, calcd. for C17H17FN2O2S (M+ H)+: 333.1068.

(E)-3-(tert-Butylimino)-2-methyl-2,3-dihydrobenzo[d]iso-thiazole 1,1-dioxide (5e): Light yellow solid; mp 100–102 8C;IR (KBr): n= 2971, 2360, 1664, 1312, 1246, 1192, 980,756 cm�1; 1H NMR (400 MHz, CDCl3): d=8.07 (d, J=7.6 Hz, 1 H), 7.84 (d, J=8.0 Hz, 1 H), 7.69–7.61 (m, 2 H), 3.0-ACHTUNGTRENNUNG(s, 3 H), 1.43 (s, 9 H); 13C NMR (100 MHz, CDCl3): d=138.7, 137.6, 132.5, 131.6, 128.1, 126.0, 121.3, 53.2, 30.8, 24.4;ESI-HR-MS: m/z= 253.1009, calcd. for C12H16N2O2S (M +H)+: 253.1005.

(E)-2-(tert-Butyl)-3-(tert-butylimino)-2,3-dihydrobenzo-[d]isothiazole 1,1-dioxide (5f): White solid; mp 101–103 8C;IR (KBr): n= 2969, 2361, 1665, 1307, 1196, 1119, 990,539 cm�1; 1H NMR (400 MHz, CDCl3): d=7.98 (d, J=7.6 Hz, 1 H), 7.71 (d, J=7.2 Hz, 1 H), 7.62–7.53 (m, 2 H),1.70 (s, 9 H), 1.43 (s, 9 H); 13C NMR (100 MHz, CDCl3): d=139.1, 138.3, 132.0, 131.3, 127.8, 124.9, 120.5, 59.4, 53.8, 30.6,27.9; ESI-HR-MS: m/z= 317.1281, calcd. for C15H22N2O2S(M+ Na)+: 317.1294.

(E)-3-(tert-Butylimino)-2-propyl-2,3-dihydrobenzo[d]iso-thiazole 1,1-dioxide (5g): Light yellow oil; IR (KBr): n=2969, 2357, 1665, 1515, 1461, 1312, 1236, 1181, 1007, 544;1H NMR (400 MHz, CDCl3): d=8.08 (d, J= 8.0 Hz, 1 H),7.87 (d, J=7.2 Hz, 1 H), 7.70–7.62 (m, 2 H), 3.56 (t, J=7.4 Hz, 1 H), 1.79–1.70 (m, 2 H), 1.45ACHTUNGTRENNUNG(s, 9 H), 0.92 (t, J=7.4 Hz, 1 H); 13C NMR (100 MHz, CDCl3): d=138.3, 137.9,132.4, 131.6, 128.3, 125.7, 121.4, 53.2, 40.7, 30.9, 21.3, 11.4;ESI-HR-MS: m/z= 281.1311, calcd. for C14H20N2O2S (M +H)+: 281.1318.

(E)-3-(tert-Butylimino)-2-isopropyl-2,3-dihydrobenzo[d]-isothiazole 1,1-dioxide (5h): Light yellow solid; mp 102–104 8C; IR (KBr): n=2972, 2360, 1658, 1301, 1225, 1196,1135, 1008, 751, 541 cm�1; 1H NMR (400 MHz, CDCl3): d=8.06 (d, J=7.6 Hz, 1 H), 7.82 (d, J= 6.8 Hz, 1 H), 7.68–7.60(m, 2 H), 4.59–4.49 (m, 1 H), 1.53 ACHTUNGTRENNUNG(s, 6 H), 1.47 ACHTUNGTRENNUNG(s, 9 H), 0.92 (t,J=7.4 Hz, 1 H); 13C NMR (100 MHz, CDCl3): d= 138.4,137.9, 132.3, 131.5, 128.3, 125.2, 121.0, 53.4, 46.4, 30.9, 19.6;ESI-HR-MS: m/z= 281.1310, calcd. for C14H20N2O2S (M +H)+: 281.1318.

(E)-3-(tert-Butylimino)-2-cyclohexyl-2,3-dihydrobenzo[d]-isothiazole 1,1-dioxide (5i): White solid; mp 133–135 8C; IR(KBr): n=2932, 2360, 1663, 1310, 1223, 1177, 1066,757 cm�1; 1H NMR (400 MHz, CDCl3): d=8.08 (d, J=6.8 Hz, 1 H), 7.88–7.86 (m, 1 H), 7.69–7.62 (m, 2 H), 4.24–

4.17 (m, 1 H), 2.16–2.02 (m, 4 H), 1.90–1.83 (m, 2 H), 1.67–1.63 (m, 1 H), 1.50 (s, 9 H), 1.37–1.20 (m, 3 H) . 13C NMR(100 MHz, CDCl3): d= 138.3, 137.6, 132.2, 131.5, 128.2,125.1, 121.0, 54.6, 53.3, 30.8, 29.6, 26.3, 25.4; ESI-HR-MS:m/z= 321.1642, calcd. for C17H24N2O2S (M+ H)+: 321.1631.

(E)-2-Benzyl-3-(tert-butylimino)-2,3-dihydrobenzo[d]iso-thiazole 1,1-dioxide (5j): White solid; mp 139–141 8C; IR(KBr): n=2970, 2356, 1669, 1311, 1236, 1178, 1059,741 cm�1; 1H NMR (400 MHz, CDCl3): d=8.05 (d, J=7.2 Hz, 1 H), 7.88 (d, J=6.8 Hz, 1 H), 7.66–7.59 (m, 2 H),7.47 (d, J= 7.6 Hz, 2 H), 7.28–7.17 (m, 3 H), 4.80 (s, 2 H),1.34 (s, 9 H); 13C NMR (100 MHz, CDCl3): d= 138.0, 137.8,136.7, 132.5, 131.7, 128.5, 128.3, 127.8, 126.9, 125.3, 121.4,53.4, 42.1, 30.6; ESI-HR-MS: m/z=329.1311, calcd. forC18H20N2O2S (M+H)+: 329.1318.

(E)-2-(4-Chlorophenyl)-3-(isopropylimino)-2,3-dihydro-benzo[d]isothiazole 1,1-dioxide (5k): Light yellow oil; IR(KBr): n=2979, 2358, 1636, 1315, 1235, 1203, 1146, 1015,765, 578 cm�1; 1H NMR (400 MHz, CDCl3): d=7.82 (d, J=7.6 Hz, 1 H), 7.61 (t, J= 7.6 Hz, 1 H), 7.38–7.30 (m, 3 H),6.84–6.80 (m, 3 H), 4.71–4.64 (m, 1 H), 1.64 (d, J= 7.2 Hz,6 H); 13C NMR (100 MHz, CDCl3): d=146.8, 142.9, 137.3,132.9, 132.6, 129.7, 128.9, 126.7, 124.3, 121.1, 120.8, 47.7,19.7; ESI-HR-MS: m/z= 335.0621, calcd. for C16H16ClN2O2S(M+ H)+: 335.0616.

(E)-3-(Butylimino)-2-(4-chlorophenyl)-2,3-dihydrobenzo-[d]isothiazole 1,1-dioxide (5m): Light yellow oil; IR (KBr):n=2968, 2354, 1638, 1315, 1231, 1186, 1145, 1017, 731,561 cm�1; 1H NMR (400 MHz, CDCl3): d=7.86 (d, J=7.6 Hz, 1 H), 7.63 (t, J=7.6 Hz, 1 H), 7.38 (t, J= 7.6 Hz, 1 H),7.30 (d, J=8.4 Hz, 2 H), 6.86–6.81 (m, 3 H), 3.81 (t, J=7.0 Hz, 2 H), 1.88–1.85 (m, 2 H), 1.46–1.40 (m, 2 H), 0.95 (t,J=7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d= 146.7,143.2, 136.8, 133.0, 132.6, 130.0, 129.0, 126.7, 124.5, 121.4,121.0, 39.7, 29.9, 20.0, 13.5; ESI-HR-MS: m/z= 349.0765,calcd. for C17H18ClN2O2S (M+ H)+: 349.0772.

(E)-2-(4-Chlorophenyl)-3-[(2-morpholinoethyl)imino]-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide (5n): Yellow oil; IR(KBr): n=2983, 2368, 1663, 1321, 1214, 1197, 1145, 1026,781, 532 cm�1; 1H NMR (400 MHz, CDCl3): d=7.85 (d, J=7.6 Hz, 1 H), 7.63 (t, J=7.6 Hz, 1 H), 7.38 (t, J= 7.6 Hz, 1 H),7.32–7.28 (m, 2 H), 6.86–6.79 (m, 3 H), 3.95 (t, J= 6.8 Hz,2 H), 3.75–3.56 (m, 4 H), 2.80 (t, J=6.8 Hz, 2 H),2.64–2.43(m, 4 H); 13C NMR (100 MHz, CDCl3): d=146.5, 143.2,136.7, 133.1, 132.7, 129.6, 129.1, 126.7, 124.4, 121.5, 120.9,66.8, 60.2, 55.8, 53.5; ESI-HR-MS: m/z= 406.0983, calcd. forC19H21ClN3O3S (M+H)+: 406.0987.

(E)-2-(4-Chlorophenyl)-3-(cyclohexylimino)-2,3-dihydro-benzo[d]isothiazole 1,1-dioxide (5o): Yellow oil; IR (KBr):n=2970, 2347, 1641, 1498, 1325, 1191, 1141, 986, 798,721 cm�1; 1H NMR (400 MHz, CDCl3): d=7.81 (d, J=8.0 Hz, 1 H), 7.60 (t, J= 7.6 Hz, 1 H), 7.37–7.29 (m, 3 H),6.83–6.80 (m, 3 H), 4.40–4.26 (m, 1 H), 2.27–2.12 (m, 4 H),1.93–1.79 (m, 2 H), 1.74–1.56 (m, 1 H), 1.42–1.18 (m, 3 H);13C NMR (100 MHz, CDCl3): d=146.9, 142.8, 137.2, 132.8,132.5, 129.6, 128.8, 126.7, 124.2, 121.0, 120.8, 55.5, 29.7, 26.1,25.1; ESI-HR-MS: m/z= 375.0926, calcd. for C19H20ClN2O2S(M+ H)+: 375.0929.

(E)-2-(4-Chlorophenyl)-3-((2,6-dimethylphenyl)imino)-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide (5p): Yellowsolid; mp 125–128 8C; IR (KBr): n= 2922, 2354, 1670, 1497,1371, 1083, 760, 698 cm�1; 1H NMR (400 MHz, CDCl3): d=




7.96 (d, J=7.6 Hz, 1 H), 7.63–7.39 (m, 6 H), 7.12–7.01 (m,3 H), 6.63 (d, J= 7.6 Hz, 1 H), 2.07 (s, 6 H); 13C NMR(100 MHz, CDCl3): d= 151.0, 145.9, 134.0, 133.8, 132.6,132.0, 131.5, 129.8, 129.4, 129.3, 128.4, 126.4, 124.4, 123.9,123.8, 18.3; ESI-HR-MS: m/z =397.0781, calcd. forC21H18ClN2O2S (M+H)+: 397.0772.

(E)-2-(4-Chlorophenyl)-3-[(4-methoxyphenyl)imino]-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide (5q): Yellow solid;mp 47–49 8C; IR (KBr): n=2930, 2357, 1658, 1489, 1412,1242,1125, 671 cm�1; 1H NMR (400 MHz, CDCl3): d= 7.95(d, J= 7.2 Hz, 1 H), 7.60 (t, J= 7.6 Hz, 1 H), 7.48 (s, 4 H),7.40 (t, J=7.6 Hz, 1 H), 6.95–6.88 (m, 4 H), 6.81 (d, J=7.6 Hz, 1 H), 3.85 (s, 3 H); 13C NMR (100 MHz, CDCl3): d=156.8, 151.4, 141.6, 133.6, 133.2, 132.3, 132.0, 131.9, 129.3,129.1, 125.8, 123.9, 120.7, 114.7, 55.5; ESI-HR-MS: m/z=399.0572, calcd. for C21H16ClSN2O3 (M+ H)+: 399.0565.

(E)-1-[6-(tert-Butylimino)phenanthridin-5(6H)-yl]ethan-one (8a): White solid; mp 193–195 8C; IR (KBr): n= 3744,2972, 2363, 1664, 1364, 1326, 1195, 766 cm�1; 1H NMR(400 MHz, CDCl3): d=8.65 (d, J= 8.4 Hz, 1 H), 8.58 (d, J=8.0 Hz, 1 H), 8.23 (d, J=8.0 Hz, 1 H), 8.14 (d, J= 8.0 Hz,1 H), 7.88 (t, J= 7.6 Hz, 1 H), 7.78–7.69 (m, 3 H), 1.63 (s,3 H), 1.49 (s, 9 H); 13C NMR (100 MHz, CDCl3): d= 170.7,155.0, 143.1, 134.6, 131.3, 130.4, 129.1, 127.8, 126.0, 124.2,122.5, 122.0, 59.5, 28.5, 25.4; ESI-HR-MS: m/z= 315.1459,calcd. for C19H20N2O (M +Na)+: 315.1468.

(E)-[6-(tert-Butylimino)phenanthridin-5(6H)-yl] ACHTUNGTRENNUNG(phenyl)-methanone (8b): White solid; mp 165–167 8C; IR (KBr): n=2967, 2360, 1651, 1342, 1190, 762 cm�1; 1H NMR (400 MHz,CDCl3): d=8.39–8.36 (m, 2 H), 8.23–8.21 (m, 1 H), 8.13–8.11(m, 1 H), 7.69–7.57 (m, 4 H), 7.23–7.20 (m, 2 H), 6.80–6.73(m, 3 H), 1.65 ACHTUNGTRENNUNG(s, 9 H); 13C NMR (100 MHz, CDCl3): d=171.2, 154.0, 142.4, 138.7, 134.0, 131.0, 129.9, 128.7, 128.2,127.4, 127.3, 127.0, 126.8, 126.4, 126.2, 123.6, 121.9, 121.7,60.1, 28.6; ESI-HR-MS: m/z =355.1810, calcd. forC24H22N2O (M+ H)+: 355.1805.

N-(tert-Butyl)phenanthridin-6-amine (9a):[18c] Light yellowsolid; mp 92–94 8C; IR (KBr): n= 3741, 2960, 2359, 1583,1522, 1425, 1213, 757, 722 cm�1; 1H NMR (400 MHz,CDCl3): d= 8.55 (d, J= 8.4 Hz, 1 H), 8.42 (d, J=8.0 Hz, 1 H),8.00 (d, J=8.0 Hz, 1 H), 7.83 (d, J= 8.4 Hz, 1 H), 7.77–7.69(m, 2 H), 7.60 (t, J=7.6 Hz, 1 H), 7.45 (t, J=7.4 Hz, 1 H),5.35(br. s, 1 H), 1.85 (s, 9 H); 13C NMR (100 MHz, CDCl3):d= 152.1, 144.7, 133.7, 129.5, 128.5, 127.3, 126.6, 122.6, 122.1,121.7, 121.7, 120.1, 119.5, 51.8, 29.3; MS (EI): m/z=77, 110,140, 151, 166, 178, 194, 235, 250.

N-(2,4,4-Trimethylpentan-2-yl)phenanthridin-6-amine(9b): Light yellow oil; IR (KBr): n= 3743, 2952, 2360, 1522,1425, 1383, 1223, 757, 720 cm�1; 1H NMR (400 MHz,CDCl3): d= 8.56 (d, J= 8.0 Hz, 1 H), 8.40 (d, J=8.0 Hz, 1 H),7.92 (d, J=8.0 Hz, 1 H), 7.82 (d, J=8.0 Hz, 1 H), 7.73 (t, J=8.0 Hz, 1 H), 7.67–7.59 (m, 2 H), 7.40 (t, J= 7.4 Hz, 1 H), 5.36(br. s, 1 H), 2.27 (s, 2 H), 1.84 (s, 6 H), 1.16 (s, 9 H); 13C NMR(100 MHz, CDCl3): d= 152.0, 144.8, 133.8, 129.5, 128.5,127.3, 126.7, 122.8, 122.0, 121.7, 121.6, 120.1, 119.7, 55.8,51.6, 31.8, 31.7, 29.8; ESI-HR-MS: m/z= 307.2157, calcd. forC21H26N2 (M+H)+: 307.2169.

N-Cyclohexylphenanthridin-6-amine (9c): Light yellowsolid; mp 83–85 8C; IR (KBr): n= 3743, 2927, 2851, 2360,1582, 1523, 1427, 758, 722 cm�1; 1H NMR (400 MHz,CDCl3): d= 8.50 (d, J= 8.0 Hz, 1 H), 8.33 (d, J=8.0 Hz, 1 H),7.84–7.81 (m, 2 H), 7.12 (t, J= 7.6 Hz, 1 H), 7.59–7.54 (m,

2 H), 7.33 (t, J=7.6 Hz, 1 H), 5.26(br. s, 1 H), 4.77–4.39 (m,1 H), 2.73–2.36 (m, 2 H), 1.84–1.70 (m, 3 H), 1.61–1.50 (m,2 H), 1.36–1.27 (m, 3 H); 13C NMR (100 MHz, CDCl3): d=152.2, 145.0, 133.9, 129.8, 128.7, 126.9, 126.7, 122.7, 122.1,121.7, 120.4, 119.2, 49.2, 33.3, 25.9, 25.0; ESI-HR-MS: m/z=277.1615, calcd. for C19H20N2 (M+ H)+: 277.1699.

N-(2,6-Dimethylphenyl)phenanthridin-6-amine (9d): Lightyellow solid; mp 201–203 8C; IR (KBr): n= 3743, 3425, 2922,2360, 1509, 761, 723 cm�1; 1H NMR (400 MHz, DMSO-d6):d= 8.87 (br. s, 1 H), 8.71–8.68 (m, 2 H), 8.47 (d, J= 8.0 Hz,1 H), 7.88 (t, J= 7.4 Hz, 1 H), 7.76 (t, J=7.4 Hz, 1 H), 7.46–7.36 ACHTUNGTRENNUNG(m, 2 H), 7.30–7.16 ACHTUNGTRENNUNG(m, 4 H), 2.20 (s, 6 H); 13C NMR(100 MHz, DMSO-d6): d=152.2, 144.6, 137.6, 136.1, 133.5,130.6, 128.6, 127.7, 127.4, 126.4, 125.9, 123.9, 122.7, 122.3,122.2, 120.3, 118.8, 18.4; ESI-HR-MS: m/z =299.1529, calcd.for C21H18N2 (M+ H)+: 299.1543.

N-(tert-Butyl)dibenzo ACHTUNGTRENNUNG[b,f]ACHTUNGTRENNUNG[1,4]oxazepin-11-amine (10a):Light yellow solid; mp 105–107 8C; IR (KBr): n=3743, 3431,2963, 2360, 1616, 1513, 1478, 1216, 756 cm�1; 1H NMR(400 MHz, CDCl3): d=7.42–7.37 (m, 2 H), 7.24–7.05 (m,5 H), 6.94–6.90 (m, 1 H), 4.57 (br. s, 1 H), 1.59 (s, 9 H);13C NMR (100 MHz, CDCl3): d=161.0, 155.1, 151.8, 141.6,132.3, 127.2, 127.0, 126.9, 125.4, 125.0, 123.0, 120.8, 120.2,52.2, 29.0; ESI-HR-MS: m/z =267.1497, calcd. forC17H18N2O (M+ H)+: 267.1492.

N-(2,4,4-Trimethylpentan-2-yl)dibenzo ACHTUNGTRENNUNG[b,f] ACHTUNGTRENNUNG[1,4]oxazepin-11-amine (10b): Yellow solid; mp 44–46 8C; IR (KBr): n=3855, 3743, 2953, 2361, 1620, 1514, 1384, 1224, 759, 680,516 cm�1; 1H NMR (400 MHz, CDCl3): d=7.40–7.34 (m,2 H), 7.20–7.03 (m, 5 H), 6.92–6.88 (m, 1 H), 4.54 (br. s, 1 H),2.07 (s, 2 H), 1.60 (s, 6 H), 1.08 (s, 9 H); 13C NMR (100 MHz,CDCl3): d=161.1, 154.9, 151.8, 141.7, 132.2, 127.2, 127.0,126.9, 125.4, 125.1, 122.8, 121.0, 120.2, 56.2, 50.6, 31.8, 31.6,29.7; ESI-HR-MS: m/z =323.2104, calcd. for C21H26N2O(M+ H)+: 323.2118.

N-Cyclohexyldibenzo ACHTUNGTRENNUNG[b,f]ACHTUNGTRENNUNG[1,4]oxazepin-11-amine (10c):Light yellow solid; mp 149–151 8C; IR (KBr): n=3450, 2361,1646, 1513, 1110, 618 cm�1; 1H NMR (400 MHz, CDCl3): d=7.43–7.37 (m, 2 H), 7.21–7.13 (m, 3 H), 7.10–7.02 (m, 2 H),6.93–6.89 (m, 1 H), 4.63 (br. s, 1 H), 4.20–4.00 (m, 1 H), 2.20–2.16 (m, 2 H), 1.78–1.73 (m, 2 H), 1.68–1.63 (m, 1 H), 1.51–1.41 (m, 2 H), 1.31–1.20 (m, 3 H); 13C NMR (100 MHz,CDCl3): d=161.0, 155.7, 151.9, 141.5, 132.5, 127.0, 126.9,126.5, 125.5, 125.1, 123.2, 120.9, 120.3, 49.4, 33.0, 25.9, 24.9;ESI-HR-MS: m/z =293.1638, calcd. for C19H20N2O (M+H)+: 293.1648.

Acknowledgements

We thank the National Natural Science Foundation of China(20932002), National Basic Research Program of China (973Program) (No. 2011CB808600), Guangdong Natural ScienceFoundation (No. 10351064101000000) and the FundamentalResearch Funds for the Central Universities (2010ZP0003)for financial support.




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[16] In ref.[9d] , alkylamines failed to give the corresponding(imino)isoindolin-1-ones.

[17] CCDC 862364 contains the supplementary crystallo-graphic data for this paper (compound 4e). These datacan be obtained free of charge from The CambridgeCrystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

[18] For selected examples of syntheses of phenanthridinesand dibenzooxazepines, see: a) D. Tsvelikhovsky, S. L.Buchwald, J. Am. Chem. Soc. 2011, 133, 14228; b) Y.Liu, R. Song, C. Wu, L. Gong, M. Hu, Z. Wang, Y. Xie,J. Li, Adv. Synth. Catal. 2012, 354, 347; c) J. Albert, L.




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[19] S. H Cho, J. Yoon, S. Chang, J. Am. Chem. Soc. 2011,133, 5996 and references cited therein.




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