Lewis Acids Catalyzed Annulations of Ynamides with Acyl Chlorides

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Lewis Acids Catalyzed Annulations of Ynamides with Acyl Chlorides for Constructing 4-Amino-2-Naphthol Derivatives and 3-Aminocyclobutenones Cheng Peng, Jingyi Zhang, Jian Xue, Siqi Li, Xiao-Na Wang, and Junbiao Chang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01255 • Publication Date (Web): 06 Jul 2018 Downloaded from http://pubs.acs.org on July 6, 2018

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The Journal of Organic Chemistry

Lewis Acids Catalyzed Annulations of Ynamides with Acyl Chlorides for Constructing 4-Amino-2-Naphthol Derivatives and 3Aminocyclobutenones Cheng Peng, Jingyi Zhang, Jian Xue, Siqi Li, Xiao-Na Wang,* and Junbiao Chang* Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, and College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P. R. China Supporting Information Placeholder

ABSTRACT: Two complimentary synthetic manifestations leading to R2 R1 O highly-substituted 1-naphthol and 2-naphthol derivatives via Lewis R2 R2 1 EWG O acids catalyzed annulations of ynamides with acyl chlorides are R Cl Ar Ar N R3 [Pd] ZnI 2 described here. A one-pot synthesis of 4-amino-2-naphthol derivatives O R2 = H R 2 = H, aryl, R3 R4 is accomplished via ZnI2-catalyzed tandem Friedel−Crafts reaction alkyl N R4 O R4 N 3 EWG R EWG sequence. While in the presence of Pd(0) catalyst, a [2 + 2] up to 95% yield up to 86% yield cycloaddition reaction of ynamides with mono-substituted ketenes that 27 examples 21 examples were generated from the dehydrohalogenation of suitable acyl chlorides leads to efficient formation of 3-aminocyclobutenones, which were subsequently modified to generate 3-amino-1-naphthols in excellent yields.

INTRODUCTION 2-Naphthol and its derivatives are key structural components in numerous natural products and pharmacologically active molecules, and have been widely used as building blocks in the field of chemistry as well as in the area of medicinal sciences.1−3 As important naphthol derivatives, 4-amino-2naphthol and its derivatives show various biological activities. For instance (Figure 1), A has high ability to scavenge oxygen-derived free radicals, and can be used as antioxidant and anticancer agent allowing for its observed inhibition effect on human cancer cell A-549 and human liver cancer cell Bel7402,3a B can be used as an inhibitor of catechol O-Me transferase (COMT) in the potential treatment of diseases such as Parkinson's disease.3b Other noteworthy examples include C, a covalent inhibitor of both Y181C and K103N/Y181C HIV-1 reverse transcriptase (RT),3c and KEAP-1 modulator D for the treatment of diabetes, obesity, dyslipidemia and related disorders.3d As such, exploring new methods for the synthesis of 4-amino-2-naphthols with certain substitution patterns is of significant importance. Although several approaches have been established for the construction of 4-substituted 2-naphthols,4 most of them suffer from lengthy procedures, low yields and narrow substrate scopes. Recently, Oh discovered an optimized protocol for the synthesis of 4-substituted 2-naphthols via the regioselective formation of β-chlorovinyl ketone intermediates.5 Later, the similar β-chlorovinylogous amide intermediates were observed by us during acylium ion-induced annulation of ynamides.6 Motivated by the significant limitations in the preparation of 4-substituted 2-naphthols, we began to

investigate the potential use of β-chlorovinylogous amides as synthetic precursors to 4-amino-2-naphthol derivatives. To the best of our knowledge, the synthesis of 4-amino-2-naphthols derivatives from ynamides has never been realized. Furthermore, if successful, this strategy would allow for a concomitant construction of two C−C bonds over the known method6 of C−C and C−O bonds formations between ynamides and chlorides. OH

O OH

N Me Me

NH O

Me

N

OH NO 2

Me

antioxidant and anticancer agent (A)

COMT inhibitor (B) O

Me NC

O

O

OH

O N N O

O NH

Me O

covalent HIV-1 RT inhibitor (C)

HN

O S O

Me

Me

Me

Me

Me

KEAP-1 modulator (D)

Figure 1. Selected biologically active 4-amino-2-naphthol and its derivatives.

Cyclobutenones are a unique class of compounds, and sever as valuable synthetic intermediates that participate in a variety of novel and useful synthetic transformations, due to their high reactivity driven by strain release.7 The most direct and

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convenient approach employed to access cyclobutenones is the [2 + 2] cycloaddition of alkynes with ketenes.8 As we known, unactivated alkynes only combine with highly electrophilic ketenes such as dichloroketene,9 and activated alkynes such as silyoxy-, or alkoxy-substituted acetylenes have been successfully employed in the cycloaddition with ketenes.10 Although a few examples of [2 + 2] cycloaddition of aminosubstituted alkynes such as ynamines with ketenes have also been reported, these reactions are complicated by the formation of allenyl amides.11 Later, Danheiser and coworkers used ynamides12 instead of ynamines to suppress the allene byproducts, and firstly realized the [2 + 2] cycloaddition of N-methoxycarbonyl-substituted ynamide with dimethylketene (generated in siu via the dehydrohalogenation of isobutyl chloride),13 However, the Danheiser’s protocol is limited to the reaction of isobutyl chloride and gives very low yields over the formation of 3-aminocyclobutenones from other acyl chlorides.14 Recently, the triethylamine-promoted [2 + 2] cycloadditions of ketenes with N-alkynylated sulfoximines and 1-alkynyltriazenes were realized by Bolm and Severin respectively,15 and further exploring the [2 + 2] cycloaddition of ketenes with ynamides is necessary. Scheme 1. Lewis Acids Catalyzed Annulations of Acyl Chlorides with Ynamides This work: EWG

R2 R1

O + Cl

N

R2

R3

R1

OH

ZnI2

R2 = H, aryl, 4 alkyl R

R4

Cl

R4

N 3 EWG R β -chlorovinylogous amides

[Pd]

R2

R1

O

EWG

N

R3

R2 = H R1

EWG

N

R3 [2 + 2]

EWG Ar N R3

•

O

R4

O

R4

∆

EWG N 3 R

R1

R

4

OH

Herein, we reported a one-pot synthesis of 4-amino-2naphthol derivatives, which was accomplished by an intermolecular Friedel−Crafts acylation of ynamides followed by an intramolecular Friedel−Crafts alkylation of βchlorovinylogous amide intermediates under ZnI2 catalyst. While in the presence of Pd(0) catalyst, a [2 + 2] cycloaddition reaction of ynamides with mono-substituted ketenes, that were generated from the dehydrohalogenation of suitable acyl chlorides, leads to efficient formation of 3-aminocyclobutenones. Moreover, when we heated up the aminocyclobutenones, the ensuing pericyclic ring-opening/ringclosure products gave very different aminonaphthols in terms of regiochemistry from the ZnI2-catalyzed process (Scheme 1).

RESULTS AND DISCUSSION We initiated our investigation by the reaction of phenylacetyl chloride 1a with ynamide 2a (Table 1). After screening of the catalysts such as SnCl4, ZnI2, ZnBr2, ZnCl2, Zn(OTf)2, and AlCl3, we isolated 4-amino-2-naphthol derivative 4a in 51% yield with the hydrohalogenation adduct of ynamide as byproduct under the catalyst ZnI2 (entries 1− −7). Further investigation showed that there appears to be noticeable stoichiometry and temperature effects: when the proportion of phenylacetyl chloride 1a was reduced from 3.0

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equiv to 2.2 equiv (entry 8), or the reaction temperature was increased from 0 oC to 80 oC, the yield was improved significantly; further stoichiometry decrease or temperature increase led to poor results (entries 9 and 13). It is noted that the reaction at 0 oC resulted in the preferential formation of a 1.7:1 mixture of (Z)- and (E)-β-chlorovinylogous amide 3a (entry 10), the emergence of 4-amino-2-naphthol derivative 4a as an exclusive product was evident upon increasing the reaction temperature to 40 oC. Table 1. Condition Optimization Friedel− −Crafts Reaction Ts O Cl

N

Bn

Me 1a

the

Tandem O

O ZnI 2

+

of

Ts 3a

2a

O Me

Cl +

Me

CH 2Cl 2 temp

N

Bn

Bn

Ts

N

Bn 4a

entrya

acid [equiv]

n[equiv of 1a]

temp [oC]

yield 3a [%]b

yield 4a [%]b

1

SnCl4 [1.0]

3.0

40

0

40

2

ZnI2 [1.0]

3.0

40

0

48

3

ZnBr2 [1.0]

3.0

40

0

24

4

ZnCl2 [1.0]

3.0

40

0

30

5

Zn(OTf)2 [1.0]

3.0

40

0

0[c]

6

AlCl3 [1.0]

3.0

40

0

trace

7

ZnI2 [0.5]

3.0

40

0

51

8

ZnI2 [0.2]

2.2

40

0

67

9

ZnI2 [0.5]

1.0

40

0

41 10

75

10

ZnI2 [0.5]

2.2

0

54 (1.7:1)d

11

ZnI2 [0.5]

2.2

60

0

12

ZnI2 [0.5]

2.2

80

0

80

13e

ZnI2 [0.5]

2.2

100

0

65

a Unless otherwise noted, reactions were carried out using 1a, 2a (0.20 mmol) with ZnI2 in CH2Cl2 (2.0 mL) under N2. bIsolated yields. c93% yield of hydrohalogenation product was obtained. dThe ratio of (Z) and (E)-β -chlorovinylogous amide 3a. eDCE was used as solvent.

With the optimized reaction conditions, we next turned our attention to assessing the scope of this reaction (Scheme 2). It was found that ynamides bearing electron-withdrawing, and electron-donating sulfonyl systems, were compatible with the reaction conditions giving high yields of the desired 4-amino2-naphthol derivatives (4a− −d). Other N-alkyl and alkenylsubstituted ynamides or alkyl and aryl-terminated ynamides also afforded the annulation products (4e− −k) with good to high yields even for the bulkier phenyl and p-tolyl-substituted ynamides. And even more surprisingly, the high-reactive NMs-substituted ynamide underwent highly effective annulation to give 4-amino-2-naphthol derivative 4l in a high yield. Subsequently, we turned our attention to assessing the scope of the acyl chlorides in this annulation. Pleasingly, various substituted phenylacetyl chlorides reacted smoothly with ynamides 2 and produced the desired products (4m−q) in good yields. It is worth mentioning that the disubstituted acetyl chlorides such as 2,2-diphenylacetyl chloride and 2phenylbutanoyl chloride could also generate the corresponding products (4r−u) in high yields.


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Scheme 2. Synthesis of 4-Amino-2-Naphthol Derivatives EWG

R2 1

R

O

R3

N

1

O

Ph

O Me EWG

R EWG

N

Bn

Ts

4a: EWG = Ts, 80% 4b: EWG = Cs, 78% 4c: EWG = Ns, 71% 4d: EWG = Mbs, 72%

N

Me

Ph O

20 10c

4

——

K3PO4 [3.0]

28

5

K3PO4 [3.0]

65

6

Pd(dppf)Cl2•CH2Cl2 Pd(dppf)Cl2•CH2Cl2

K3PO4 [5.0]

71

7

Pd(PPh3)4

K3PO4 [5.0]

35

8

PdCl2

K3PO4 [5.0]

36

9

Pd(OAc)2

K3PO4 [5.0]

39

Me

Me N Ts Bu

EWG

Me

4m: 67%

R4 N

4

4r: EWG = Ts, R = Me, 73% 4s: EWG = Ms, R 4 = n-hex, 79%

Cl

Bn

Et O R4 EWG

N

10

Pd2(dba)3

K3PO4 [5.0]

37

11

Pd(dppe)Cl2

K3PO4 [5.0]

41

12

Pd(PPh3)2Cl2

K3PO4 [5.0]

80

13

Pd(PPh3)2Cl2

K2CO3 [5.0]

57

14

Pd(PPh3)2Cl2

Na2CO3 [5.0]

54

15

Pd(PPh3)2Cl2

Cs2CO3 [5.0]

trace

16

Pd(PPh3)2Cl2

NEt3 [5.0]

trace

17

Pd(PPh3)2Cl2

pyridine [5.0]

12

18d

Pd(PPh3)2Cl2

K3PO4 [5.0]

87

Et

Ph

Bn

O

4p: EWG = Ts, R 4 = Me, 61% 4q: EWG = Ms, R4 = n-hex, 56%

O R4 N

16

——

O Me

Ph

—— NEt3 [3.0]

O

EWG

yield [%]b

——

Cl

4n: EWG = Ts, R4 = Me, 65% 4o: EWG = Ms, R4 = n-hex, 68%

base [equiv]

Pd(dppf)Cl2•CH2Cl2

O

Me

catalyst

2

O R Me N EWG Bn

entrya

O

Me

4O

5a

3

4l: 85%

X-ray of 4a

Me

O

4h: R4 = n-Pr, 86% 4i: R4 = n-hex, 86% 4j: R4 = Ph, 65% 4k: R4 = Tol, 63%

Ph

Bn

Ts N Bn

Pd(PPh3)4

O n-hex Ms

Ph

Ph

base, CH2Cl2, 60 oC Me 2a

1a

Me

O

+

catalyst (20 mol%)

1

N

Ts

, 71%

Bn

Bn

R3

4g: R3 =

N

Cl

R4

4e: R3 = Me, 70% 4f: R3 = Bu, 82%

Ts O

Ph

O

Ph

O Me N

Ar

4O

R3 4

2 O

R O

CH2Cl2, 80 oC R4

Table 2. Condition Optimization of the [2 + 2] Cycloaddition Reaction.

2

ZnI2 (0.5 equiv)

+

Cl

N

R

R1

2

Ph O

Bn R4

4t: EWG = Ts, = Me, 72% 4u: EWG = Ms, R4 = n-hex, 86%

During the observation of the Pd-catalyzed tandem FriedelCrafts reaction of phenylacetyl chloride 1a with ynamide 2a, we were especially excited by the discovery that 3aminocyclobutenone 5a was formed as a byproduct. As shown in Table 2, Under the catalyst palladium complexes, 3aminocyclobutenone 5a was isolated in about 20% yield, and no β-chlorovinylogous amide 3a or 4-amino-2-naphthol derivative 4a was obtained (entries 1 and 2). Using triethylamine (the reported approach13−15 to the synthesis of cyclobutenones from ynamides and their analogues) resulted in a low yield, and only 10% yield of 3-aminocyclobutenone 5a was obtained with 85% of 2a recovered (entry 3). Inorganic bases such as K3PO4, etc. were attempted but the effect of improving the yield is insignificant producing lots of hydrohalogenation product of ynamide (entry 4). Then several palladium complexes with base were investigated (entries 5−12), though single palladium complexes could also afford the desired product 5a (entries 1 and 2), the yield could be further improved by adding K3PO4 as an additional base (entries 5, 6 vs. 2, entry 7 vs. entry 1). Finally, Pd(PPh3)2Cl2 was found to promote the annulation most efficiently, delivering 3-aminocyclobutenone 5a in 80% yield (entry 12). Meanwhile, the base was varied (entries 13−17), it was immediately clear that the strength of the base played a significant role in the reaction, with K3PO4 giving the highest yield of 5a. Further investigation showed that the yield increased to 87% when 4 Å MS was added (entry 18).

a Unless otherwise noted, reactions were performed in a vial with 1a (0.40 mmol), 2a (0.20 mmol), catalyst (0.04 mmol) and base in CH2Cl2 (2.0 mL) under N2. bIsolated yields. c85% of 2a was recovered. d4 Å MS (30 mg) was added.

Holding suitable conditions in hand, the generality of this annulation reaction has been studied (Scheme 3). Ynamides with electron-withdrawing and electron-donating sulfonyl systems were initially surveyed, the reaction proceeded smoothly delivering the desired 3-aminocyclo-butenones (5a− −c) in high yields, and a good yield was obtained for the formation of 5d, most likely due to the high reactivity of NMbs-substituted ynamide 2d, that led to more byproduct of hydrohalogenation reaction. And we also found that ynamide 2d resulted in a lower yield at 60 oC compared with 80 oC, this loss of yield is probably due to the higher temperature improving the reactivity of annulation reaction, thereby significantly suppressing the hydrohalogenation reaction to the byproduct. A similar phenomenon also occurred for the formation of 5l. Next, other N-aryl-, alkenyl-, and alkylsubstituted ynamides or alkyl- and aryl-terminated ynamides were perfectly tolerated under these reaction conditions, leading to the desired annulation products (5e− −m) with good to excellent yields. And we were also pleased to find that this annulation was amenable to the synthesis of 3aminocyclobutenone 5n using the thienyl-terminated ynamide 2n, albeit in a high yield. The high-reactive N-Ms-substituted ynamide 2o generated the corresponding 3-aminocyclobutenone 5o in a moderate yield. Subsequently, various substituted phenylacetyl chlorides were tested and reacted smoothly with ynamides 2 leading to the desired 3-



aminocyclobutenones (5p− −z) in good to high yields. Moreover, the use of phenylpropanoyl chloride 1' also afforded the annulation product 5'. Scheme 3. Synthesis of 3-Aminocyclobutenonesa EWG O

Ar

N

R3

Pd(PPh3)2Cl 2 (0.2 equiv) K3PO4 (5.0 equiv)

+ R 2

1

EWG N R3

Ar

N O

4

OH N

5 Cs N Bn

Ph

OMe NO2

Ns N Bn

Ph

OMe

OMe

TMEM16A CaCC inhibitor (E)

O

Me 5a: 87% Mbs N Bn

Ph

Ts N Ph

Ph

Ts N Me

Ts N Bn

Ph

O Me 5c: 83%

Ts N

Ph

O

Ts N Bn

Ph

Ts N Bu

Ph

O Me 5f: 75%

O Me 5e: 74%

O Me 5d: 73% b (63%)a Ph

O Me 5b: 87%

X-ray of 5a

Me 5g: 71%

Scheme 4. Synthesis of Aminonaphthols R2

R1

Me 5h: 63%

O

Mbs N Bn

Ph

O

PMP

O

Ts N Bn

Ph

Ph

5l: 78%b

n-Pr 5i: 78%

O

(67%)a

O

R

Tol

PMP

Me

O

5p: 78%

Ts N Bn

O

PMP

O

Ph

5q: 79%

Mbs N Bn

O Me

Ts N Me Cl O

Me

5x: 60%

Me

5v: 71%

Me

Ts N Bn Me

O Me 5y: 70%

3

R

R2

R2 OH

OH

Me N Ts Bn 6r: R 2 = Ph, 82% 6t: R2 = Et, 83%

n-hex N Ms Bn 6s: R 2 = Ph, 81% 6u: R 2 = Et, 83%

EWG N R1

1,4-dioxane, 110 oC

EWG N 1 R

R

R2 O Me 5s: 60%

R2

O Ts N

Cl R

1

Me O

Me

5w: 67%

Bn

Ts N Bn Me 5': 33%

a

Unless otherwise specified, reactions were carried out using 1 (0.40 mmol), 2 (0.20 mmol), Pd(PPh3)2Cl2 (0.04 mmol), K3PO4 ( 1.0 mmol) and 4 Å MS (30 mg) in CH2Cl2 (2.0 mL) under N2. bReactions were run at 80 o C without 4 Å MS.

Next, we turned our attention to the transformations of 4amino-2-naphthol derivatives 4 and 3-aminocyclobutenones 5, which are viable substrates for the synthesis of naphthols. Just the same as 2- naphthols, 1-naphthol derivatives are also privileged scaffolds in various natural products as well as in the area of pharmaceutically active compounds,16 For examples (Figure 2), 3-amino-1-naphthol derivatives E and F can be used as a selective inhibitor of the TMEM16A calciumactivated chloride channel (CaCC) and an anti-inflammatory agent respectively.16d,e 4-Amino-2-naphthol derivatives 4 were converted into the corresponding 4-amino-2-naphthols 6 in high yields,17 and 3-aminocyclobutenones 5 were

OH 7

5

Ts N Bu

O O n-hex 5z: 62%

N 6

R

Me Ts N Bn

R4 EWG

6a: 89%

Cl O

Me

5u: 89%

MeOH, 90

oC

R 4

Bn

Ts N Bn

Tol

Cl

Cl

O Me 5t: 55%b

Cl Ts N Bn

Ts N

Ts N Bn

N

OH

NaOH (10.0 equiv)

3

5o: 55%

5r: 79%

Cl

n-hex

Ar

4O

Me Ts

R2

R1

OH

Ms N Bn

Ph

5n: 91%

N

Ph 5k: 92%

S

O

5m: 95%

Ts N Bn

O

n-hex 5j: 90% Ts Ph N Bn

R2 O

EWG O

anti-inflammatory agent (F)

Figure 2. Selected biologically active 3-amino-1-naphthol derivatives.

Ts N Bn

Ph

N

OMe

H N

R4

O

Ts N Bn

Ph

subsequently modified using benzannulation strategy comprising a 4π-electrocyclic ring opening followed by 6πelectrocyclic ring closure and tautomerization domino process to generate 3-amino-1-naphthols 7 in almost quantitative yields (Scheme 4).18

4 Å MS, CH 2Cl2, 60 oC

Cl

Page 4 of 10

OH 7a: R 1 = Bn, >95% 7f: R1 = , 93%

Ts N

Me Bn

Me OH 7u: >95%

Ts N

Bn

Me Me OH 7y: >95%

CONCLUSIONS In conclusion, we discovered a ZnI2-catalyzed tandem Friedel−Crafts reaction of ynamides that readily allows the synthesis of 4-amino-2-naphthol derivatives through the regioselective formation of β-chlorovinylogous amide intermediates, and also developed a Pd(0)-catalyzed [2 + 2] cycloaddition reaction of ynamides leading highly efficient formation of 3-aminocyclobutenones. These two reactions provide general and straightforward ways to construct 2naphthol derivatives and cyclobutenones in good to excellent yields, and tolerate wide ranges of functional groups. More importantly, thermal rearrangements of the 3aminocyclobutenones give very different aminonaphthols in terms of regiochemistry from the ZnI2-catalyzed process, they are complementary. Further studies on the construction of other heterocyclic and carbocyclic systems via the reactions of ynamides are ongoing and will be reported in due course.

EXPERIMENTAL SECTION


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All reaction were performed in oven-dried glassware under a nitrogen atmosphere. Solvents were distilled prior to use. Chromatographic separations were performed using 200~300 mesh silica gel. 1H NMR and 13 C NMR spectra were obtained on a 400 NMR spectrometer using CDCl3 as solvent with TMS or residual solvent as standard unless otherwise noted. Infrared spectra were obtained on a FT/IR spectrophotometer and relative intensities are expressed qualitatively as s (strong), m (medium), and w (weak). TLC analysis was performed using 254 nm polyesterbacked plates and visualized using UV and KMnO4 stain. High-resolution mass spectra (HRMS) were performed on a MicrOTOF-Q II mass spectrometer. General Procedure for the Condition Optimization of Tandem Friedel-Crafts Reaction. To an oven-dried sealed tube were added ynamide 2a (59.9 mg, 0.20 mmol), CH2Cl2 (2.0 mL, ynamide concn = 0.10 M) and the specified Lewis acid, then phenylacetyl chloride 1a was added at 0 °C. The reaction vessel was capped and stirred at the specified temperature. After the reaction was judged to be complete by TLC, the reaction mixture was cooled to rt, filtered through a pad of silica gel, concentrated in vacuo, and purified by flash silica gel column chromatography [gradient eluent: 13:1~6:1 petroleum ether/EtOAc] to afford product 4a or products 3a and 4a. Entry 13: β-chlorovinylogous amide 3a (48.9 mg, 54%), 3a-Z: 23.5 mg; Rf = 0.49 [4:1 petroleum ether/EtOAc], colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.51 (s, 3H), 2.47 (s, 3H), 3.77 (d, 2H, J = 14.5 Hz), 3.96 (d, 1H, J = 13.3 Hz), 4.85 (d, 1H, J = 13.3 Hz), 7.06-7.08 (m, 2H), 7.22-7.24 (m, 1H), 7.26-7.28 (m, 2H), 7.34-7.37 (m, 7H), 7.79 (d, 2H, J = 8.3 Hz); 13C NMR (100 MHz, CDCl3) δ 18.2, 21.9, 48.8, 51.8, 123.7, 127.4, 128.5, 128.7, 128.79, 128.81, 129.8, 129.9, 130.0, 132.8, 134.1, 135.3, 144.2, 144.8, 202.1; IR (neat) (cm-1) 1702w, 1354m, 1275s, 1261s, 1164s; HRMS (ESI): m/z calcd for C25H24ClNO3SNa [M+Na]+: 476.1058; found 476.1060. 3a-Z and 3a-E: (Z/E = 1/2.5) 25.3 mg; Rf = 0.49 [4:1 petroleum ether/EtOAc], colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.51 (s, 3.0H), 1.90 (s, 7.5H), 2.47 (s, 3.0H), 2.48 (s, 7.5H), 3.47 (d, 2.5H, J = 16.3 Hz), 3.77 (d, 2.0H, J = 4.9 Hz), 3.60 (d, 2.5H, J = 16.3 Hz), 3.97 (d, 1.0H, J = 13.3 Hz), 4.22 (d, 2.5H, J = 13.3 Hz), 4.83-4.89 (m, 3.5H), 6.91-6.94 (m, 5.0H), 7.06-7.09 (m, 2.0H), 7.18-7.25 (m, 8.5H), 7.26-7.28 (m, 2.0H), 7.32-7.41 (m, 24.5H), 7.78-7.82 (m, 7.0H); 13C NMR (100 MHz, CDCl3) (3a-Z): δ 18.2, 21.9, 48.8, 51.8, 123.7, 127.4, 128.5, 128.7, 128.79, 128.81, 129.8, 129.9, 130.0, 132.8, 134.1, 135.3, 144.2, 144.8, 202.1; (3a-E): δ 18.9, 21.9, 47.8, 52.8, 126.8, 128.4, 128.8, 128.9, 129.0, 129.96, 129.98, 130.5, 131.9, 133.5, 134.2, 134.6, 142.0, 145.1, 199.1, IR (neat) (cm-1) 1702w, 1354m, 1275s, 1261s, 1164s; HRMS (ESI): m/z calcd for C25H24ClNO3SNa [M+Na]+: 476.1058; found 476.1060. General Procedure for the Synthesis of 4-Amino-2-Naphthol Derivatives. To an oven-dried sealed tube were added ynamide 2a (59.9 mg, 0.20 mmol), CH2Cl2 (2.0 mL, ynamide concn = 0.10 M) and ZnI2 (31.9 mg, 0.1mmol), then phenylacetyl chloride 1a (58.3 µL, 0.44 mmol) was added at 0 °C. The reaction vessel was capped and stirred at 80 oC. After the reaction was judged to be complete by TLC, the reaction mixture was cooled to rt, filtered through a pad of silica gel, concentrated in vacuo, and purified by flash silica gel column chromatography [gradient eluent: 13:1~6:1 petroleum ether/EtOAc] to afford 4-amino-2-naphthol derivative 4a (85.2 mg, 0.16 mmol) in 80% yield. 4a: (85.2 mg, 80%); Rf = 0.40 [4:1 petroleum ether/EtOAc]; white solid; mp = 48− −49 oC; 1H NMR (400 MHz, CDCl3) δ 1.57 (s, 3H), 2.40 (s, 3H), 3.83 (s, 2H), 4.54 (d, 1H, J = 14.0 Hz), 4.95 (d, 1H, J = 14.0 Hz), 6.976.99 (m, 2H), 7.09-7.23 (m, 7H), 7.28-7.35 (m, 6H), 7.48 (s, 1H), 7.637.69 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 13.2, 21.7, 41.5, 55.4, 120.4, 124.1, 125.9, 126.0, 127.5, 127.7, 128.0, 128.1, 128.3, 128.8, 129.5, 129.8, 130.09, 130.11, 132.6, 133.4, 133.9, 134.3, 135.3, 138.1, 143.6, 147.8, 169.6; IR (neat) (cm-1) 1756s, 1496s, 1343s, 1230s, 1157s, 1115s; HRMS (ESI): m/z calcd for C33H29NO4SNa [M+Na]+: 558.1710; found 558.1717. 4b: (86.6 mg, 78%); Rf = 0.20 [6:1 petroleum ether/EtOAc]; white solid; mp = 157− −158 oC; 1H NMR (400 MHz, CDCl3) δ 1.54 (s, 3H), 3.85 (s, 2H), 4.57(d, 1H, J = 13.9 Hz), 4.96 (d, 1H, J = 13.9 Hz), 7.01 (d, 2H, J = 6.8 Hz), 7.11-7.22 (m, 5H), 7.30-7.41 (m, 8H), 7.50 (s, 1H), 7.65-7.67 (m, 2H), 7.70 (d, 1H, J = 8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 13.3, 41.5, 55.8, 120.7, 123.8, 126.1, 126.2, 127.6, 128.2, 128.3, 128.5, 128.9, 129.2, 129.45, 129.47, 129.9, 130.2, 132.7, 133.3, 133.8, 134.0, 135.1, 139.3, 139.5, 147.8, 169.6; IR (neat) (cm-1) 1766m, 1349s, 1236m, 1160s, 1113s, 1093s; HRMS (ESI): m/z calcd for C32H26ClNO4SNa [M+Na]+: 578.1163; found 578.1157. 4c: (80.4 mg, 71%); Rf = 0.10 [6:1 petroleum ether/EtOAc]; white solid; mp = 175− −176 oC; 1H NMR (400 MHz, CDCl3) δ 1.52 (s, 3H), 3.86 (s, 2H), 4.62 (d, 1H, J = 13.9 Hz), 5.01 (d, 1H, J = 13.9 Hz), 7.03-7.12 (m,

4H), 7.14-7.18 (m, 2H), 7.22-7.25 (m, 1H), 7.31-7.37 (m, 6H), 7.54 (s, 1H), 7.73 (d, 1H, J = 8.2 Hz), 7.86-7.88 (m, 2H), 8.24-8.26 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 13.4, 41.5, 56.2, 121.1, 123.3, 124.4, 126.31, 126.33, 127.7, 128.4, 128.58, 128.60, 128.9, 129.0, 129.5, 129.6, 130.2, 132.8, 133.27, 133.31, 134.0, 134.7, 146.6, 147.8, 150.1, 169.7; IR (neat) (cm-1) 2921m, 1755m, 1533s, 1351s, 1313m, 1233s; HRMS (ESI): m/z calcd for C32H26N2O6S Na [M+Na]+: 589.1404; found 589.1398. 4d: (79.4 mg, 72%); Rf = 0.19 [4:1 petroleum ether/EtOAc]; white solid; mp = 156− −157 oC; 1H NMR (400 MHz, CDCl3) δ 1.58 (s, 3H), 3.850 (s, 2H), 3.855 (s, 3H), 4.56 (d, 1H, J = 14.0 Hz), 4.95 (d, 1H, J = 14.0 Hz), 6.91 (d, 2H, J = 8.9 Hz), 6.98-7.01 (m, 2H), 7.10-7.22 (m, 5H), 7.27-7.36 (m, 6H), 7.50 (s, 1H), 7.67-7.71 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 13.3, 41.5, 55.4, 55.8, 114.3, 120.4, 124.1, 125.97, 126.05, 127.6, 128.07, 128.12, 128.4, 128.9, 129.5, 129.9, 130.1, 130.2, 132.7, 132.8, 133.4, 133.9, 134.4, 135.5, 147.8, 163.1, 169.7; IR (neat) (cm-1) 1756m, 1595m, 1496s, 1341s, 1275s, 1261s, 1231m; HRMS (ESI): m/z calcd for C33H29NO5SNa [M+Na]+: 574.1659; found 574.1651. 4e: (63.3 mg, 70%); Rf = 0.11 [6:1 petroleum ether/EtOAc]; white solid; mp = 111− −112 oC; 1H NMR (400 MHz, CDCl3) δ 2.01 (s, 3H), 2.44 (s, 3H), 3.26 (s, 3H), 3.92 (s, 2H), 7.26-7.34 (m, 4H), 7.36-7.43 (m, 6H), 7.53 (s, 1H), 7.66 (d, 2H, J = 8.3 Hz), 7.72-7.75 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 13.1, 21.7, 38.0, 41.7, 120.3, 123.8, 126.3, 126.5, 127.66, 127.71, 128.1, 128.9, 129.6, 129.8, 130.5, 132.0, 132.7, 133.4, 137.1, 137.5, 143.6, 147.9, 169.9; IR (neat) (cm-1) 1760s, 1339s, 1219s, 1174m, 1153m, 1128s, 1094s; HRMS (ESI): m/z calcd for C27H25NO4S Na [M+Na]+: 482.1397; found 482.1391. 4f: (81.8 mg, 82%); Rf = 0.19 [6:1 petroleum ether/EtOAc]; white solid; mp = 132− −133 oC; 1H NMR (400 MHz, CDCl3) δ 0.80 (t, 3H, J = 7.3 Hz), 1.14-1.21 (m, 2H), 1.45-1.60 (m, 2H), 2.01 (s, 3H), 2.42 (s, 3H), 3.49-3.67 (m, 2H), 3.92 (s, 2H), 7.19-7.24 (m, 3H), 7.30-7.44 (m, 7H), 7.53 (s, 1H), 7.60-7.62 (m, 2H), 7.72 (d, 1H, J = 8.1 Hz); 13C NMR (100 MHz, CDCl3) δ 13.79, 13.81, 20.2, 21.7, 31.5, 41.7, 52.2, 120.3, 124.4, 126.1 (2C), 127.7, 127.8, 128.0, 128.9, 129.6, 129.7, 130.8, 132.7, 132.8, 133.4, 135.5, 137.8, 143.5, 147.9, 169.8, one carbon missing due to overlap; IR (neat) (cm-1) 1751s, 1598w, 1495m, 1456m, 1348s, 1229s, 1155s; HRMS (ESI): m/z calcd for C30H31NO4SNa [M+Na]+: 524.1866; found 524.1850. 4g: (68.9 mg, 71%); Rf = 0.16 [6:1 petroleum ether/EtOAc]; white solid; mp = 110− −111 oC; 1H NMR (400 MHz, CDCl3) δ 2.00 (s, 3H), 2.43 (s, 3H), 3.91 (s, 2H), 4.10-4.16 (m, 1H), 4.28-4.34 (m, 1H), 4.89-4.96 (m, 2H), 5.82-5.92 (m, 1H), 7.20-7.25 (m, 3H), 7.30-7.43 (m, 7H), 7.53 (s, 1H), 7.63 (d, 2H, J = 8.3 Hz), 7.71-7.73 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9, 21.7, 41.7, 54.8, 119.7, 120.4, 124.3, 126.1, 126.2, 127.6, 127.8, 128.0, 128.9, 129.6, 129.8, 130.8, 132.6, 132.8, 133.0, 133.4, 135.1, 137.8, 143.7, 147.8, 169.8; IR (neat) (cm-1) 1756s, 1343s, 1231m, 1162s, 1114s, 1088s; HRMS (ESI): m/z calcd for C29H27NO4SNa [M+Na]+: 508.1533; found 508.1554. 4h: (96.8 mg, 86%); Rf = 0.17 [6:1 petroleum ether/EtOAc]; white solid; mp = 134− −135 oC; 1H NMR (400 MHz, CDCl3) δ 0.57 (t, 3H, J = 7.2 Hz), 1.23-1.35 (m, 2H), 1.99 (td, 1H, J = 12.9 Hz, 4.5 Hz), 2.12 (td, 1H, J = 12.8 Hz, 4.5 Hz), 2.44 (S, 3H), 3.85 (s, 2H), 4.58 (d, 1H, J = 14.1 Hz), 4.92 (d, 1H, J = 14.1 Hz), 6.97-6.99 (m, 2H), 7.06-7.20 (m, 5H), 7.24 (s, 2H), 7.29-7.37 (m, 6H), 7.52 (s, 1H), 7.66-7.70 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 15.0, 21.7, 22.4, 30.6, 41.8, 55.7, 121.2, 124.5, 125.91, 125.95, 127.6, 128.02, 128.04, 128.1, 128.4, 128.9, 129.5, 129.8, 130.09, 130.11, 132.7, 133.3, 133.9, 135.4, 137.8, 138.0, 143.7, 147.8, 169.7; IR (neat) (cm-1) 1756s, 1496s, 1455s, 1342s, 1233m, 1218s, 1157s; HRMS (ESI): m/z calcd for C35H33NO4SNa [M+Na]+: 586.2023; found 586.2025. 4i: (103.7 mg, 86%); Rf = 0.24[6:1 petroleum ether/EtOAc]; white solid; mp = 117− −118 oC; 1H NMR (400 MHz, CDCl3) δ 0.69-0.76 (m, 1H), 0.861.07 (m, 7H), 1.19-1.32 (m, 3H), 2.02 (td, 1H, J = 12.9, 4.5 Hz), 2.14 (td, 1H, J = 13.0, 4.6 Hz),2.43 (s, 3H), 3.85 (s, 2H), 4.60 (d, 1H, J = 14.2 Hz), 4.90 (d, 1H, J = 14.1 Hz), 7.00-7.02 (m, 2H), 7.08-7.13 (m, 3H), 7.157.23 (m, 4H), 7.29-7.37 (m, 6H), 7.51 (s, 1H), 7.65-7.69 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 14.4, 21.7, 22.9, 28.6, 29.2, 30.3, 31.7, 41.8, 55.8, 121.3, 124.5, 125.90, 125.94, 127.6, 128.00, 128.02, 128.1, 128.4, 128.9, 129.5, 129.8, 130.1, 130.2, 132.7, 133.3, 133.9, 135.5, 137.9, 138.0, 143.7, 147.8, 169.7; IR (neat) (cm-1) 1756s, 1343s, 1276s, 1261s, 1229m, 1158s, 1117s; HRMS (ESI): m/z calcd for C38H39NO4SNa [M+Na]+: 628.2492; found 628.2481. 4j: (77.7 mg, 65%); Rf = 0.13 [6:1 petroleum ether/EtOAc]; white solid; mp = 56− −57 oC; 1H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), 3.31 (d, 1H, J = 15.7 Hz), 3.37 (d, 1H, J = 15.7 Hz), 4.45 (d, 1H, J = 14.1 Hz), 4.65 (d, 1H, J = 14.2 Hz), 6.04 (d, 1H, J = 7.7 Hz), 6.51 (d, 2H, J = 6.7 Hz), 6.936.95 (m, 2H), 7.02 (t, 3H, J = 7.6 Hz), 7.12-7.18 (m, 3H), 7.22-7.25 (m, 4H), 7.26-7.42 (m, 5H), 7.45-7.49 (m, 1H), 7.59 (s, 1H), 7.81 (d, 1H, J =



8.2 Hz), 7.92 (d, 1H, J = 8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 21.7, 40.8, 55.2, 121.4, 125.6, 126.7, 126.8, 127.2, 127.4, 127.6, 127.8, 128.20, 128.22, 128.3, 128.6, 128.7, 129.4, 129.5, 130.3, 130.8, 131.3, 133.1, 133.8, 134.3, 134.7, 137.4, 137.9, 143.7, 147.0, 170.0; IR (neat) (cm-1) 1756s, 1495m, 1329s, 1321s, 1231s, 1213s, 1158s; HRMS (ESI): m/z calcd for C38H31NO4SNa [M+Na]+: 620.1866; found 620.1857. 4k: (77.1 mg, 63%); Rf = 0.13 [6:1 petroleum ether/EtOAc]; white solid; mp = 47− −48 oC; 1H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 2.44 (s, 3H), 3.36 (d, 1H, J = 15.5 Hz), 3.41 (d, 1H, J = 15.5 Hz), 4.42 (d, 1H, J = 14.1 Hz), 4.68 (d, 1H, J = 14.2 Hz), 6.02 (dd, 1H, J = 7.8, 1.9 Hz), 6.55 (d, 2H, J = 7.8 Hz), 6.82 (d, 1H, J = 7.8 Hz), 6.93-6.96 (m, 2H), 6.99-7.05 (m, 3H), 7.11-7.16 (m, 3H), 7.22-7.25 (m, 4H), 7.25-7.27 (m , 2H), 7.30-7.35 (m, 1H), 7.43-7.47 (m, 1H), 7.58 (s, 1H), 7.79 (d, 1H, J = 7.9 Hz), 7.85 (d, 1H, J = 8.6 Hz); 13C NMR (100 MHz, CDCl3) δ 21.6, 21.8, 40.9, 55.3, 121.3, 125.6, 126.5, 126.7, 127.1, 128.09, 128.14, 128.3, 128.50, 128.54, 128.6, 129.36, 129.44, 130.3, 131.0, 131.1, 131.2, 133.1, 133.7, 134.7, 134.9, 137.1, 137.6, 137.8, 143.5, 147.2, 170.1; IR (neat) (cm-1) 1758m, 1496m, 1334s, 1215s, 1113s , 1089s; HRMS (ESI): m/z calcd for C39H33NO4SNa [M+Na]+: 634.2023; found 634.2016. 4l: (90.0 mg, 85%); Rf = 0.11 [6:1 petroleum ether/EtOAc]; yellow solid; mp = 112− −113oC; 1H NMR (400 MHz, CDCl3) δ 0.88 (t, 3H, J = 7.3 Hz), 1.02-1.12 (m, 4H), 1.22-1.37 (m, 4H), 2.19-2.26 (m, 1H), 2.322.39 (m, 1H), 3.01 (s, 3H), 3.88 (s, 2H), 4.68 (d, 1H, J = 14.2 Hz), 4.89 (d, 1H, J = 14.2 Hz), 7.10-7.13 (m, 2H), 7.19-7.25 (m, 3H), 7.31-7.40 (m, 5H), 7.42-7.45 (m, 2H), 7.56 (s, 1H), 7.74-7.77 (m , 1H), 7.83-7.85 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.3, 22.8, 28.8, 29.5, 30.4, 31.8, 41.78, 41.83, 56.4, 121.3, 123.9, 126.3, 126.9, 127.6, 128.4, 128.5, 128.7, 128.9, 129.4, 130.3, 130.4, 132.8, 133.2, 134.9, 135.4, 137.2, 147.8, 169.8; IR (neat) (cm-1) 1744s, 1497w, 1329s, 1238s, 1228s, 1146s, 1125s; HRMS (ESI): m/z calcd for C32H35NO4SNa [M+Na]+: 552.2179; found 552.2178. 4m: (74.7 mg, 67%); Rf = 0.27 [6:1 petroleum ether/EtOAc]; white solid; mp = 50− −51 oC; 1H NMR (400 MHz, CDCl3) δ 0.81 (t, 3H, J = 7.2 Hz), 1.19 (s, 3H), 1.25-1.34 (m, 4H), 2.32 (s, 3H), 2.33 (s, 3H), 2.43 (s, 3H), 2.59 (s, 3H), 2.94 (s, 3H), 3.48-3.55 (m, 1H), 3.85 (s, 2H), 3.94-4.01 (m, 1H), 7.02-7.04 (m, 1H), 7.10 (d, 2H, J = 8.2 Hz), 7.19 (d, 1H, J = 7.3 Hz), 7.23-7.25 (m, 3H), 7.51 (d, 2H, J = 8.2 Hz), 7.68 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 12.8, 13.9, 19.4, 20.3, 20.7, 21.1, 21.7, 24.8, 29.3, 39.3, 50.7, 118.0, 127.2, 127.9, 128.6, 129.9, 130.5, 131.26, 131.29, 131.9, 132.0, 132.4, 132.6, 133.3, 133.67, 133.75 (2C), 135.9, 137.0, 143.4, 146.8, 169.8, one carbon missing due to overlap ; IR (neat) (cm-1) 1754m, 1343s, 1276s, 1261s, 1162s, 1126s, 1105s; HRMS (ESI): m/z calcd for C34H39NO4SNa [M+Na]+: 580.2492; found 580.2495. 4n: (73.5 mg, 65%); Rf = 0.20 [6:1 petroleum ether/EtOAc]; white solid; mp = 47− −48 oC; 1H NMR (400 MHz, CDCl3) δ 1.06 (s, 3H), 2.30 (s, 6H), 2.42 (s, 3H), 2.58 (s, 3H), 2.65 (s, 3H), 3.81 (s, 2H), 4.83 (d, 1H, J = 14.2 Hz), 4.90 (d, 1H, J = 14.1 Hz), 7.00-7.03 (m, 1H), 7.06-7.19 (m, 9H), 7.23 (s, 2H), 7.61 (d, 2H, J = 8.3 Hz), 7.68 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 19.3, 20.4, 21.1, 21.7, 24.4, 39.2, 57.5, 118.3, 127.1, 128.1, 128.3, 128.4, 128.5, 129.8, 130.5, 130.8, 131.2, 131.4, 131.9, 132.3, 132.4, 132.51, 132.52, 133.6, 133.8, 134.7, 135.0, 135.8, 138.1, 143.5, 147.1, 169.8; IR (neat) (cm-1) 1754m, 1341s, 1231m, 1210m, 1156s, 1127m, 1091s; HRMS (ESI): m/z calcd for C37H37NO4SNa [M+Na]+: 614.2336; found 614.2326. 4o: (79.6 mg, 68%); Rf = 0.20 [6:1 petroleum ether/EtOAc]; white solid; mp = 59− −60 oC; 1H NMR (400 MHz, CDCl3) δ 0.86 (t, 3H, J = 7.3 Hz), 1.04-1.11 (m, 2H), 1.19-1.34 (m, 6H), 1.87-1.94 (m, 1H), 2.09-2.16 (m, 1H), 2.34 (s, 3H), 2.37 (s, 3H), 2.60 (s, 3H), 2.84 (s, 3H), 3.07 (s, 3H), 3.88 (s, 2H), 4.40 (d, 1H, J = 14.6 Hz), 5.01 (d, 1H, J = 14.5 Hz), 6.966.98 (m, 2H), 7.03-7.05 (m, 1H), 7.12 (d, 2H, J = 7.9 Hz), 7.17-7.24 (m, 5H), 7.75 (t, 1H, J = 17.5 Hz); 13C NMR (100 MHz, CDCl3) δ 14.3, 19.5, 20.4, 21.1, 22.9, 25.0, 29.4, 29.9, 30.1, 31.9, 39.6, 41.6, 57.7, 119.2, 127.2, 128.5, 128.7, 130.4, 130.7, 131.2, 131.3, 131.5 (2C), 131.6, 131.7, 133.1, 133.8, 133.9, 134.7, 135.3, 135.9, 137.3, 147.1, 170.0, one carbon missing due to overlap; IR (neat) (cm-1) 1753w, 1332m, 1276s, 1261s, 1143s, 1110s; HRMS (ESI): m/z calcd for C36H43NO4SNa [M+Na]+: 608.2805; found 608.2810. 4p: (73.6 mg, 61%); Rf = 0.14 [6:1 petroleum ether/EtOAc]; white solid; mp = 49− −50 oC; 1H NMR (400 MHz, CDCl3) δ 1.65 (s, 3H), 2.46 (s, 3H), 3.82 (s, 2H), 4.47 (d, 1H, J = 13.9 Hz), 5.02 (d, 1H, J = 13.9 Hz), 6.84 (s, 1H), 7.01 (d, 2H, J = 6.6 Hz), 7.13-7.24 (m, 4H), 7.27-7.35 (m, 6H), 7.46 (s, 1H), 7.63 (t, 3H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3) δ 13.5, 21.8, 40.8, 55.6, 120.3, 123.1, 127.0, 127.6, 128.3, 128.5, 129.1, 129.6, 130.0, 130.2, 130.6, 130.8, 130.9, 131.7, 132.4, 133.67, 133.69, 135.2, 135.8, 138.0, 144.2, 148.0, 169.1; IR (neat) (cm-1) 1753m, 1493m, 1340m,

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1218w, 1160m, 1122s; HRMS (ESI): m/z calcd for C33H27Cl2NO4SNa [M+Na]+: 626.0930; found 626.0925. 4q: (66.9 mg, 56%); Rf = 0.17 [6:1 petroleum ether/EtOAc]; white solid; mp = 48− −49 oC; 1H NMR (400 MHz, CDCl3) δ 0.89 (t, 3H, J = 7.3 Hz), 1.02-1.16 (m, 4H), 1.23-1.37 (m, 4H), 2.22-2.29 (m, 1H), 2.34-2.42 (m, 1H), 3.04 (s, 3H), 3.86 (s, 2H), 4.74 (d, 1H, J = 14.2 Hz), 4.78 (d, 1H, J = 14.2 Hz), 7.10-7.13 (m, 2H), 7.21-7.24 (m, 2H), 7.27-7.38 (m, 6H), 7.53 (s, 1H), 7.68 (d, 1H, J = 8.7 Hz), 7.73 (d, 1H, J = 1.9 Hz); 13C NMR (100 MHz, CDCl3) δ 14.3, 22.9, 28.5, 29.5, 30.5, 31.8, 41.1, 41.9, 56.5, 121.2, 123.2, 127.3, 128.7, 128.8, 129.2, 129.8, 130.2, 130.8, 130.9, 131.47, 131.55, 138.2, 133.8, 134.4, 135.1, 138.3, 147.9, 169.3; IR (neat) (cm-1) 1754m, 1493s, 1333s, 1217s, 1148s, 1120s; HRMS (ESI): m/z calcd for C32H33Cl2NO4SNa [M+Na]+: 620.1400; found 620.1401. 4r: (100.2 mg, 73%); Rf = 0.21 [6:1 petroleum ether/EtOAc]; white solid; mp = 56− −57 oC; 1H NMR (400 MHz, DMSO) δ 1.48 (s, 3H), 2.45 (s, 3H), 4.71 (d, 1H, J = 14.2 Hz), 4.91 (d, 1H, J = 14.2 Hz), 5.09 (s, 1H), 6.96-7.01 (m, 6H), 7.10-7.14 (m, 2H), 7.17-7.27 (m, 10H), 7.33 (d, 2H, J = 3.3 Hz), 7.40-7.48 (m, 6H), 7.70-7.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 13.6, 21.7, 56.6, 124.1, 125.88, 125.9, 126.7, 127.2, 127.5, 127.8, 127.9, 128.1, 128.3, 128.4, 128.5, 128.7, 128.8, 128.9, 129.8, 130.3, 130.5, 132.6, 132.8, 133.7, 135.2, 138.0, 143.6, 145.2, 170.4, six carbons missing due to overlap; IR (neat) (cm-1) 1756w, 1348m, 1157s, 1109s, 1089s, 1047m; HRMS (ESI): m/z calcd for C45H37NO4SNa [M+Na]+: 710.2336; found 710.2321. 4s: (108.1 mg, 79%); Rf = 0.14 [6:1 petroleum ether/EtOAc]; white solid; mp = 47− −48 oC; 1H NMR (400 MHz, DMSO) δ 0.81-0.93 (m, 6H), 0.95-1.01 (m, 2H), 1.13-1.23 (m, 3H), 1.99-2.07 (m, 1H), 2.19-2.27 (m, 1H), 3.28 (s, 3H), 4.68 (d, 1H, J = 14.3 Hz), 4.94 (d, 1H, J = 14.3 Hz), 5.00 (s, 1H), 6.95 (s, 2H), 7.07 (d, 4H, J = 6.6 Hz), 7.16-7.31 (m, 11H), 7.36-7.54 (m, 6H), 8.01 (d, 1H, J = 8.6 Hz); 13C NMR (100 MHz, CDCl3) δ 14.3, 22.8, 31.8, 36.2, 42.1, 43.0, 49.0, 56.3, 56.5, 123.9, 126.2, 127.1, 127.3, 127.8, 128.0, 128.41, 128.44, 128.6, 128.7, 128.9, 129.0, 130.4, 130.5, 130.8, 131.0, 132.9, 133.5, 134.2, 135.1, 135.3, 136.5, 136.9, 137.6, 138.2, 145.20, 170.8; IR (neat) (cm-1) 1756w, 1455w, 1377w, 1334m, 1147s, 1109s; HRMS (ESI): m/z calcd for C44H43NO4SNa [M+Na]+:704.2805; found 704.2807. 4t: (84.7 mg, 72%); Rf = 0.31 [6:1 petroleum ether/EtOAc]; white solid; mp = 63− −64 oC; 1H NMR (400 MHz, DMSO) δ 0.86-0.90 (m, 6H), 1.37 (s, 3H), 1.78-1.88 (m, 1H), 2.09-2.16 (m, 1H), 2.36 (d, 3H, J = 2.9 Hz), 2.552.60 (m, 2H), 3.84 (td, 1H, J = 7.6, 2.4 Hz), 4.57 (dd, 1H, J = 14.2, 9.1 Hz), 4.76 (dd, 1H, J = 14.2, 11.6 Hz), 6.83-6.85 (m, 2H), 6.99-7.13 (m, 4H), 7.23-7.37 (m, 9H), 7.58 (d, 2H, J = 8.5 Hz), 7.87 (d, 1H, J = 8.1 Hz); 13 C NMR (100 MHz, CDCl3) δ 12.42, 12.44, 21.73, 21.76, 26.1, 53.5, 55.5, 124.2, 125.5, 125.7, 127.7, 127.8, 127.9, 128.0, 128.3, 128.36, 128.40, 128.81, 128.85, 129.78, 129.83, 130.2, 131.5, 132.2, 132.3, 138.4, 143.5, 145.6, 172.1, two carbons missing due to overlap; IR (neat) (cm-1) 1750m, 1455w, 1350m, 1158s, 1125s, 1091s; HRMS (ESI): m/z calcd for C37H37NO4SNa [M+Na]+: 614.2336; found 614.2330. 4u: (101.8 mg, 86%); Rf = 0.23 [6:1 petroleum ether/EtOAc]; white solid; mp = 47－48 oC; 1H NMR (400 MHz, DMSO) δ 0.84-0.90 (m, 5H), 0.96-1.14 (m, 10H), 1.18-1.28 (m, 4H), 1.89-1.97 (m, 1H), 2.16-2.25 (m, 2H), 2.65-2.70 (m, 1H), 3.23 (d, 3H, J = 1.7 Hz), 3.90 (td, 1H, J = 7.6, 5.5 Hz), 4.64 (dd, 1H, J = 14.3, 11.7 Hz), 4.87 (dd, 1H, 14.3, 2.0 Hz), 7.01-7.05 (m, 2H), 7.13-7.22 (m, 3H), 7.32-7.37 (m, 1H), 7.39-7.52 (m, 6H), 7, 93-7.96 (m, 1H), 8.01 (td, 1H, J = 8.3, 1.4 Hz); 13C NMR (100 MHz, CDCl3) δ 12.5, 14.3, 22.9, 41.9, 42.9, 53.1, 53.73, 53.75, 56.4, 124.67, 124.74, 126.1, 126.6, 127.80, 127.83, 128.2, 128.3, 128.4, 128.66, 128.7, 128.8, 128.94, 128.97, 130.4, 131.7, 145.6, six carbons missing due to overlap; IR (neat) (cm-1) 1756w, 1334m, 1147s, 1109s, 1032w; HRMS (ESI): m/z calcd for C36H43NO4SNa [M+Na]+: 608.2805; found 608.2791. General Procedure for the Synthesis of 3-Aminocyclobuteneones. To an oven-dried seal tube were added ynamide 2a (59.9 mg, 0.20 mmol), Pd(PPh3)2Cl2 (28.1 mg, 0.04 mmol), K3PO4 (212.3 mg, 1.0 mmol), 4ÅMS (30 mg), CH2Cl2 (2.0 mL, ynamide concn = 0.10 M) and phenylacetyl chloride 1a (54.0 µL, 0.40 mmol). When the reaction was judged to be complete by TLC after stirred at 60 oC for 10.0 h, the reaction mixture was cooled to rt, filtered through a pad of silica gel, and then washed with 1.0 M Na2CO3 aqueous solution twice, dried over anhydrous Na2SO4, filtrated, concentrated in vacuo, and purified by flash silica gel column chromatography [gradient eluent: 8:1~4:1 petroleum ether/EtOAc] to afford 5a (72.5 mg, 0.17 mmol) in 87% yield. 5a: (72.5 mg, 87%); Rf = 0.24 [4:1 petroleum ether/EtOAc]; white solid; mp = 156− −157 oC; 1H NMR (400 MHz, CDCl3) δ 1.73 (s, 3H), 2.39 (s, 3H), 4.61 (d, 1H, J = 16.8 Hz), 4.71 (s, 1H), 5.06 (d, 1H, J = 16.8 Hz), 7.01-7.03 (m, 2H), 7.14-7.16 (m, 4H), 7.22-7.34 (m, 8H); 13C NMR (100


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MHz, CDCl3) δ 8.6, 21.7, 52.8, 67.4, 126.4, 126.9, 127.6, 127.8, 128.0, 128.1, 128.9, 129.0, 130.0, 135.2, 135.8, 136.0, 145.2, 160.1, 187.2; IR (neat) (cm-1) 1749s, 1604s, 1595s, 1575s, 1386s, 1297m, 1171s; HRMS (ESI): m/z calcd for C25H23NO3SNa [M+Na]+: 440.1291; found 440.1268. 5b: (76.3 mg, 87%); Rf = 0.30 [4:1 petroleum ether/EtOAc]; white solid; mp = 155− −156 oC; 1H NMR (400 MHz, CDCl3) δ 1.72 (d, 3H, J = 2.2 Hz), 4.89 (q, 1H, J = 2.0 Hz), 4.93 (d, 1H, J = 16.8 Hz), 5.14 (d, 1H, J = 16.8 Hz), 7.09-7.10 (m, 2H), 7.15-7.17 (m, 2H), 7.23-7.34 (m, 8H), 7.99 (d, 2H, J = 8.8 Hz); 13C NMR (100 MHz, CDCl3) δ 8.5, 53.2, 67.6, 124.2, 126.5 (2C), 128.1, 128.4, 128.6, 128.8, 129.1, 129.3, 135.0, 135.6, 143.7, 150.3, 159.7, 186.9, one carbon missing due to overlap; IR (neat) (cm-1) 1765s, 1621s, 1535s, 1385m, 1359s, 1352s, 1328s, 1165s; HRMS (ESI): m/z calcd for C24H20NO3SClNa [M+Na]+: 460.0745; found 460.0743. 5c: (74.6 mg, 83%); Rf = 0.19 [4:1 petroleum ether/EtOAc]; white solid; mp = 165− −166 oC; 1H NMR (400 MHz, CDCl3) δ 1.72 (d, 3H, J = 2.2 Hz), 4.89 (q, 1H, J = 2.1 Hz), 4.93 (d, 1H, J = 16.8 Hz), 5.14 (d, 1H, J = 16.8 Hz), 7.08-7.11 (m, 2H), 7.14-7.17 (m, 2H), 7.23-7.26 (m, 1H), 7.27-7.35 (m, 7H), 7.97-8.00 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 8.5, 53.2, 67.6, 124.2, 126.5 (2C), 128.1, 128.4, 128.6, 128.8, 129.1, 129.3, 135.0, 135.6, 143.7, 150.3, 159.7, 186.7, one carbon missing due to overlap; IR (neat) (cm-1) 2920m, 2851w, 1765s, 1621s, 1535s, 1358s, 1328w, 1165s; HRMS (ESI): m/z calcd for C24H20N2O5SNa [M+Na]+ 471.0985; found 471.0968. 5d: (63.3 mg, 73%); Rf = 0.14 [4:1 petroleum ether/EtOAc]; white solid; mp = 152− −153 oC; 1H NMR (400 MHz, CDCl3) δ 1.73 (d, 3H, J = 2.2 Hz), 3.83 (s, 3H), 4.63 (d, 1H, J = 16.9 Hz), 4.72 (q, 1H, J = 2.2 Hz), 5.05 (d, 1H, J = 16.9 Hz), 6.78 (d, 2H, J = 9.0 Hz), 7.04-7.06 (m, 2H), 7.13-7.15 (m, 2H), 7.24-7.33 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 8.6, 52.8, 55.9, 67.4, 114.5, 126.4, 126.6, 127.8, 128.0, 128.1, 128.9, 129.0, 129.5, 129.9, 135.9, 136.0, 160.2, 163.9, 187.2; IR (neat) (cm-1) 1749s, 1591s, 1494s, 1385s, 1261s, 1161s, 1134s; HRMS (ESI): m/z calcd for C25H23NO4SNa [M+Na]+: 456.1240; found 456.1243. 5e: (59.7 mg, 74%); Rf = 0.25 [4:1 petroleum ether/EtOAc]; white solid; mp = 132− −133 oC; 1H NMR (400 MHz, CDCl3) δ 0.95 (d, 3H, J = 2.2 Hz), 2.32 (s, 3H), 5.06 (q, 1H, J = 2.2 Hz), 6.65 (d, 2H, J = 8.4 Hz), 6.91 (d, 2H, J = 8.2 Hz), 7.14-7.16 (m, 2H), 7.26-7.28 (m, 2H), 7.33-7.35 (m, 3H), 7.38-7.46 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 6.7, 21.7, 67.4, 126.2, 127.8, 128.28, 128.30, 128.9, 129.4, 129.6, 130.2, 130.6, 133.8, 136.70, 136.74, 145.0, 161.0, 187.7; IR (neat) (cm-1) 1748s, 1594s, 1488m, 1384s, 1372s, 1347s, 1330s, 1171s; HRMS (ESI): m/z calcd for C24H21NO3SNa [M+Na]+: 426.1134; found 426.1136. 5f: (55.1 mg, 75%); Rf = 0.23 [4:1 petroleum ether/EtOAc]; white solid; mp = 79− −80 oC; 1H NMR (400 MHz, CDCl3) δ 1.86 (d, 3H, J = 2.2 Hz), 2.39 (s, 3H), 4.14 (ddt, 1H, J = 17.4, 5.5, 1.6 Hz), 4.40-4.46 (m, 1H), 4.85 (q, 1H, J = 2.2 Hz), 5.14-5.23 (m, 2H), 5.70-5.79 (m, 1H), 7.08-7.11 (m, 2H), 7.14 (d, 2H, J = 8.1 Hz), 7.22-7.25 (m, 3H), 7.26-7.28 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 8.6, 21.7, 51.4, 67.3, 118.3, 125.8, 127.7, 127.85, 127.91, 128.9, 130.0, 132.6, 135.2, 136.0, 145.2, 160.1, 187.3; IR (neat) (cm-1) 1742s, 1607s, 1594s, 1382s, 1354s, 1325s, 1162s, 1132s; HRMS (ESI): m/z calcd for C21H21NO3SNa [M+Na]+: 390.1134; found 390.1140. 5g: (54.5 mg, 71%); Rf = 0.27 [4:1 petroleum ether/EtOAc]; white solid; mp = 126− −127 oC; 1H NMR (400 MHz, CDCl3) δ 0.90 (t, 3H, J = 7.3 Hz), 1.26-1.31 (m, 2H), 1.44-1.52 (m, 1H), 1.69-1.77 (m, 1H), 1.86 (s, 3H), 2.39 (s, 3H), 3.47-3.54 (m, 1H), 3.65-3.72 (m, 1H), 4.86 (s, 1H), 7.08-7.10 (m, 2H), 7.15 (d, 2H, J = 8.1 Hz), 7.22-7.26 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 8.5, 13.8, 19.7, 21.7, 32.2, 49.7, 67.4, 125.3, 127.5, 127.80, 127.82, 128.8, 130.0, 135.3, 136.0, 145.0, 160.2, 187.4; IR (neat) (cm-1) 2920m, 2849w, 1746s, 1645m, 1589s, 1389s, 1366s, 1339s; HRMS (ESI): m/z calcd for C22H25NO3SNa [M+Na]+: 406.1447; found 406.1448. 5h: (43.0 mg, 63%); Rf = 0.14 [4:1 petroleum ether/EtOAc]; white solid; mp = 124− −125 oC; 1H NMR (400 MHz, CDCl3) δ 1.90 (d, 3H, J = 2.2 Hz), 2.40 (s, 3H), 3.31 (s, 3H), 4.85 (q, 1H, J = 2.2 Hz), 7.16 (d, 2H, J = 8.2 Hz), 7.15-7.17 (m, 2H), 7.21-7.23 (m, 2H), 7.25-7.27 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 8.6, 21.7, 36.5, 67.3, 125.3, 127.6, 127.8 (2C), 128.9, 130.0, 134.2, 136.0, 145.2, 160.8, 187.2, one carbon missing due to the overlap; IR (neat) (cm-1) 2922w, 1752s, 1593s, 1451m, 1369s, 1313s, 1166s; HRMS (ESI): m/z calcd for C19H19NO3SNa [M+Na]+: 364.0978; found 364.0972. 5i: (69.2 mg, 78%); Rf = 0.34 [4:1 petroleum ether/EtOAc]; white solid; mp = 131− −132 oC; 1H NMR (400 MHz, CDCl3) δ 0.79 (t, 3H, J = 7.3 Hz), 1.31-1.47 (m, 2H), 2.06-2.12 (m, 2H), 2.37 (s, 3H), 4.66 (d, 1H, J = 16.9 Hz), 4.78 (s, 1H), 5.03 (d, 1H, J = 16.8 Hz), 7.06-7.15 (m, 6H), 7.22-7.25 (m, 3H), 7.27-7.34 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 14.1, 21.7, 21.8, 26.1, 52.6, 67.4, 126.3, 127.6, 127.9, 128.0, 128.1, 128.8, 129.0, 129.9, 132.1, 135.1, 135.7, 136.0, 145.1, 159.3, 187.4; IR (neat) (cm-1)

1751s, 1595s, 1495w, 1378m, 1355s, 1164s; HRMS (ESI): m/z calcd for C27H27NO3SNa [M+Na]+: 468.1604; found 468.1604. 5j: (87.8 mg, 90%); Rf = 0.41 [4:1 petroleum ether/EtOAc]; white solid; mp = 112− −113 oC; 1H NMR (400 MHz, CDCl3) δ 0.85 (t, 3H, J = 7.1 Hz), 1.14-1.38 (m, 8H), 2.07-2.12 (m, 2H), 2.36 (s, 3H), 4.65 (d, 1H, J = 16.9 Hz), 4.78 (s, 1H), 5.04 (d, 1H, J = 16.9 Hz), 7.06-7.14 (m, 6H), 7.22-7.24 (m, 3H), 7.26-7.33 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 14.2, 21.7, 22.6, 24.2, 28.4, 29.3, 31.6, 52.6, 67.4, 126.3, 127.6, 127.8, 127.9, 128.0, 128.8, 128.9, 129.9, 132.3, 135.0, 135.6, 136.0, 145.1, 159.0, 187.4; IR (neat) (cm-1) 1752s, 1593s, 1381m, 1355s, 1344s, 1299w, 1162s; HRMS (ESI): m/z calcd for C30H33NO3SNa [M+Na]+: 510.2073; found 510.2092. 5k: (88.0 mg, 92%); Rf = 0.34 [4:1 petroleum ether/EtOAc]; white solid; mp = 123− −124 oC; 1H NMR (400 MHz, CDCl3) δ 2.39 (s, 3H), 4.65 (d, 1H, J = 15.9 Hz), 4.93 (d, 1H, J = 15.9 Hz), 5.17 (s, 1H), 6.46 (d, 2H, J = 7.6 Hz), 7.02-7.11 (m, 6H), 7.13-7.18 (m, 3H), 7.24-7.26 (m, 2H), 7.26-7.33 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 21.8, 51.8, 68.6, 127.6, 127.8, 128.0, 128.1, 128.3, 128.4, 128.6, 128.7 (2C), 128.9, 129.4, 130.1, 131.6, 134.2, 134.9, 135.3, 145.3, 159.0, 186.2, one carbon missing due to overlap; IR (neat) (cm-1) 1751s, 1617s, 1588s, 1378s, 1362s, 1340s, 1304m, 1170s; HRMS (ESI): m/z calcd for C30H25NO3SNa [M+Na]+: 502.1447; found 502.1445. 5l: (77.3 mg, 78%); Rf = 0.21 [4:1 petroleum ether/EtOAc]; white solid; mp = 52− −53 oC; 1H NMR (400 MHz, CDCl3) δ 3.84 (s, 3H), 4.68 (d, 1H, J = 15.9 Hz), 4.94 (d, 1H, J = 15.9 Hz), 5.18 (s, 1H), 6.46 (d, 2H, J = 7.4 Hz), 6.77 (d, 2H, J = 9.0 Hz), 7.03-7.19 (m, 7H), 7.24-7.25 (m, 2H), 7.287.31 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 51.8, 55.9, 68.6, 114.6, 127.6, 128.0, 128.1, 128.3, 128.4, 128.7 (2C), 128.8, 128.9, 129.2, 129.4, 130.2, 131.2, 134.3, 135.5, 159.1, 164.0, 186.2, one carbon missing due to the overlap; IR (neat) (cm-1) 1749m, 1592s, 1578s, 1496s, 1375s, 1341s, 1260s; HRMS (ESI): m/z calcd for C30H25NO4SNa [M+Na]+: 518.1397; found 518.1385. 5m: (93.8 mg, 95%); Rf = 0.27 [4:1 petroleum ether/EtOAc]; white solid; mp = 123− −124 oC; 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 2.38 (s, 3H), 4.63 (d, 1H, J = 15.7 Hz), 4.92 (d, 1H, J = 15.7 Hz), 5.15 (s, 1H), 6.51 (d, 2H, J = 7.3 Hz), 7.00-7.07 (m, 6H), 7.10-7.25 (m, 8H), 7.28-7.30 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 21.5, 21.7, 51.6, 68.6, 125.9, 127.7, 127.8, 127.9, 128.1, 128.3, 128.5, 128.6, 129.0, 129.2, 130.1, 131.9, 134.3, 135.0, 135.3, 138.7, 145.2, 158.6, 186.4; IR (neat) (cm-1) 1752s, 1591s, 1496m, 1375s, 1356s, 1295w, 1165s; HRMS (ESI): m/z calcd for C31H27NO3SNa [M+Na]+: 516.1604; found 516.1602. 5n: (88.4 mg, 91%); Rf = 0.19 [4:1 petroleum ether/EtOAc]; white solid; mp = 59− −60 oC; 1H NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 4.88 (d, 1H, J = 15.9 Hz), 5.02 (d, 1H, J = 15.9 Hz), 5.18 (s, 1H), 6.63 (d, 2H, J = 7.2 Hz), 6.92-6.93 (m, 1H), 6.99-7.01 (m, 1H), 7.06-7.13 (m, 6H), 7.17-7.26 (m, 4H), 7.28-7.34 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 21.8, 51.7, 68.8, 124.2, 127.2, 127.4, 127.6, 127.8, 128.07, 128.12, 128.5, 128.6, 128.7, 128.8, 129.2, 130.1, 134.4, 134.9, 135.2, 145.4, 158.8, 185.7; IR (neat) (cm-1) 1750w, 1600m, 1424m, 1366s, 1294m, 1165s, 1111m; HRMS (ESI): m/z calcd for C28H23NO3S2Na [M+Na]+: 508.1012; found 508.1002. 5o: (45.3 mg, 55%); Rf = 0.29 [4:1 petroleum ether/EtOAc]; white solid; mp = 117− −118 oC; 1H NMR (400 MHz, CDCl3) δ 0.87 (t, 3H, J = 6.9 Hz), 1.23-1.30 (m, 6H), 1.45-1.54 (m, 2H), 2.10-2.23 (m, 2H), 2.14 (s, 3H), 4.92 (s, 1H), 4.95 (d, 1H, J = 16.4 Hz), 5.03 (d, 1H, J = 16.5 Hz), 7.287.38 (m, 8H), 7.39-7.43 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 14.2, 22.7, 24.2, 28.6, 29.5, 31.6, 41.9, 52.8, 67.1, 127.0, 128.4, 128.5, 128.7, 129.1, 129.4, 130.2, 135.3, 135.7, 160.2, 187.0; IR (neat) (cm-1) 1746s, 1582s, 1434m, 1383s, 1357s, 1329s, 1159s, 1138m; HRMS (ESI): m/z calcd for C24H29NO3SNa [M+Na]+: 434.1760; found 434.1765. 5p: (69.5 mg, 78%); Rf = 0.15 [4:1 petroleum ether/EtOAc]; white solid; mp = 156− −157 oC; 1H NMR (400 MHz, CDCl3) δ 1.72 (d, 3H, J = 2.2 Hz), 2.40 (s, 3H), 3.79 (s, 3H), 4.60 (d, 1H, J = 16.8 Hz), 4.64 (q, 1H, J = 2.2 Hz), 5.05 (d, 1H, J = 16.8 Hz), 6.76 (d, 2H, J = 8.7 Hz), 6.92 (d, 2H, J = 8.6 Hz), 7.14-7.17 (m, 4H), 7.28-7.35 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 8.6, 21.7, 52.8, 55.4, 66.7, 114.3, 126.4, 126.7, 127.5, 127.7, 128.1, 128.9, 129.0, 130.0, 135.3, 136.1, 145.1, 159.5, 160.5, 187.8; IR (neat) (cm-1) 1757s, 1604s, 1514s, 1386s, 1355s, 1328s; HRMS (ESI): m/z calcd for C26H25NO4SNa [M+Na]+: 470.1397; found 470.1396. 5q: (80.5 mg, 79%); Rf = 0.19 [4:1 petroleum ether/EtOAc]; white solid; mp = 167− −168 oC; 1H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 3.83 (s, 3H), 4.62 (d, 1H, J = 15.8 Hz), 4.93 (d, 1H, J = 15.8 Hz), 5.12 (s, 1H), 6.48 (d, 2H, J = 7.2 Hz), 6.79-6.81 (m, 2H), 6.96-6.98 (m, 2H), 7.04-7.10 (m, 4H), 7.16-7.19 (m, 3H), 7.28-7.33 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 21.8, 51.8, 55.6, 68.1, 114.2, 127.4, 127.7, 127.8, 128.1, 128.3, 128.4, 128.7, 128.9, 129.4, 129.7, 130.1, 131.5, 134.3, 135.1, 145.3, 159.5,



159.6, 186.9; IR (neat) (cm-1) 1749s, 1615s, 1582s, 1377s, 1365s, 1349s, 1170s; HRMS (ESI): m/z calcd for C31H27NO4SNa [M+Na]+: 532.1553; found 532.1547. 5r: (82.3 mg, 79%); Rf = 0.20 [4:1 petroleum ether/EtOAc]; white solid; mp = 143− −144 oC; 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 3H), 2.41 (s, 3H), 3.81 (s, 3H), 4.61 (d, 1H, J = 15.7 Hz), 4.92 (d, 1H, J = 15.6 Hz), 5.10 (s, 1H), 6.53 (d, 2H, J = 7.1 Hz), 6.77 (d, 2H, J = 8.6 Hz), 6.93 (d, 2H, J = 8.6 Hz), 7.00 (d, 2H, J = 7.9 Hz), 7.05-7.25 (m, 7H), 7.34 (d, 2H, J = 8.1 Hz); 13C NMR (100 MHz, CDCl3) δ 21.6, 21.8, 51.7, 55.5, 68.1, 114.1, 126.0, 127.4, 127.8, 127.9, 128.1, 128.4, 129.0, 129.2, 129.7, 130.1, 131.9, 134.4, 135.2, 138.7, 145.2, 159.1, 159.5, 187.1; IR (neat) (cm-1) 1741s, 1626m, 1594s, 1510s, 1375s, 1363s, 1169s; HRMS (ESI): m/z calcd for C32H29NO4SNa [M+Na]+: 546.1710; found 546.1720. 5s: (54.1 mg, 60%); Rf = 0.26 [4:1 petroleum ether/EtOAc]; white solid; mp = 181− −183 oC; 1H NMR (400 MHz, CDCl3) δ 1.70 (d, 3H, J = 2.2 Hz), 2.42 (s, 3H), 4.69 (d, 1H, J = 16.8 Hz), 4.73 (q, 1H, J = 2.2 Hz), 5.08 (d, 1H, J = 16.8 Hz), 6.95 (d, 2H, J = 8.4 Hz), 7.15-7.26 (m, 6H), 7.30-7.34 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 8.6, 21.8, 52.9, 66.9, 126.4, 127.1, 127.5, 128.3, 129.0, 129.1 (2C), 130.1, 133.8, 134.5, 135.3, 135.9, 145.4, 160.0, 186.6, one carbon missing due to the overlap; IR (neat) (cm-1) 1762s, 1614s, 1492s, 1440m, 1384s, 1352s, 1162s, 1133s; HRMS (ESI): m/z calcd for C25H22NO3SClNa [M+Na]+: 474.0901; found 474.0903. 5t: (51.8 mg, 55%); Rf = 0.14 [4:1 petroleum ether/EtOAc]; white solid; mp = 157− −158 oC; 1H NMR (400 MHz, CDCl3) δ 1.69 (d, 3H, J = 2.2 Hz), 3.85 (s, 3H), 4.72 (d, 1H, J = 17.0 Hz), 4.75 (q, 1H, J = 2.2 Hz), 5.08 (d, 1H, J = 16.9 Hz), 6.79 (d, 2H, J = 8.9 Hz), 6.98 (d, 2H, J = 8.4 Hz), 7.147.15 (m, 2H), 7.21 (d, 2H, J = 8.4 Hz), 7.29-7.36 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 8.5, 52.8, 55.9, 66.8, 114.5, 126.3, 126.7, 128.2, 129.0, 129.1, 129.2, 129.5, 129.7, 133.7, 134.6, 135.9, 160.1, 164.0, 186.6; IR (neat) (cm-1) 1762s, 1614s, 1592m, 1492m, 1386m, 1352s, 1261s, 1156s; HRMS (ESI): m/z calcd for C25H22NO4SClNa [M+Na]+: 490.0850; found 490.0858. 5u: (80.0 mg, 89%); Rf = 0.31 [4:1 petroleum ether/EtOAc]; white solid; mp = 127− −128 oC; 1H NMR (400 MHz, CDCl3) δ 1.78 (d, 3H, J = 2.3 Hz), 2.42 (s, 3H), 4.57 (d, 1H, J = 16.6 Hz), 5.10 (d, 1H, J = 16.6 Hz), 5.30 (q, 1H, J = 2.3 Hz), 6.74 (d, 1H, J = 6.2 Hz), 6.98 (t, 1H, J = 7.4 Hz), 7.147.25 (m, 5H), 7.31-7.37 (m, 4H), 7.48 (d, 2H, J = 8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 8.9, 21.8, 53.4, 63.7, 126.8, 127.0, 127.5, 127.6, 128.1, 128.3, 128.9, 129.1, 130.1, 130.3, 133.4, 134.2, 135.5, 135.9, 145.3, 159.2, 185.7; IR (neat) (cm-1) 1760s, 1616s, 1600s, 1385s, 1354s, 1324s, 1163s, 1140s; HRMS (ESI): m/z calcd for C25H22NO3SClNa [M+Na]+: 474.0901; found 474.0904. 5v: (57.1 mg, 71%); Rf = 0.28 [4:1 petroleum ether/EtOAc]; white solid; mp = 84− −85 oC; 1H NMR (400 MHz, CDCl3) δ 1.87 (d, 3H, J = 2.2 Hz), 2.42 (s, 3H), 4.08 (ddt, 1H, J = 17.2, 6.0, 1.6 Hz), 4.45 (dtd, 1H, J = 6.4, 4.3, 1.9 Hz), 5.24 (t, 1H, J = 1.6 Hz), 5.27 (dt, 1H, J = 5.5, 1.7 Hz), 5.40 (q, 1H, J = 2.2 Hz), 5.75-5.85 (m, 1H), 6.86 (dd, 1H, J = 7.7, 1.7 Hz), 7.04 (td, 1H, J = 7.6, 1.3 Hz), 7.17 (td, 1H, J = 7.7, 1.7 Hz), 7.23 (d, 2H, J = 8.1 Hz), 7.37 (dd, 1H, J = 8.0, 1.3 Hz), 7.48 (d, 2H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3) δ 8.9, 21.8, 52.1, 63.5, 118.7, 127.0, 127.1, 127.60, 127.64, 128.9, 130.1, 130.3, 132.6, 133.6, 134.3, 135.5, 145.3, 159.1, 185.8; IR (neat) (cm-1) 1749s, 1583s, 1443s, 1383s, 1367s, 1350s, 1160s; HRMS (ESI): m/z calcd for C21H20NO3SClNa [M+Na]+: 424.0745; found 424.0744. 5w: (55.9 mg, 67%); Rf = 0.38 [4:1 petroleum ether/EtOAc]; white solid; mp = 88− −89 oC; 1H NMR (400 MHz, CDCl3) δ 0.92 (t, 3H, J = 7.3 Hz), 1.28-1.37 (m, 2H), 1.53-1.61 (m, 1H), 1.72-1.80 (m, 1H), 1.87 (d, 3H, J = 2.3 Hz), 2.43 (s, 3H), 3.39-3.47 (m, 1H), 3.68-3.76 (m, 1H), 5.40 (q, 1H, J = 2.3 Hz), 6.85 (dd, 1H, J = 7.7, 1.7 Hz), 7.04 (td, 1H, J = 7.6, 1.3 Hz), 7.17 (td, 1H, J = 7.7, 1.7 Hz), 7.24 (d, 2H, J = 8.1 Hz), 7.37 (dd, 1H, J = 8.0, 1.3 Hz), 7.47 (d, 2H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3) δ 8.8, 13.8, 19.8, 21.8, 32.7, 50.3, 63.5, 126.5, 127.0, 127.4, 127.6, 128.8, 130.1, 130.3, 133.6, 134.3, 135.6, 145.2, 159.4, 185.9; IR (neat) (cm-1) 1748s, 1594s, 1581s, 1391s, 1368s, 1339m, 1307s; HRMS (ESI): m/z calcd for C22H24NO3SClNa [M+Na]+: 440.1058; found 440.1060. 5x: (45.1 mg, 60%); Rf = 0.12 [4:1 petroleum ether/EtOAc]; white solid; mp = 98− −99 oC; 1H NMR (400 MHz, CDCl3) δ 1.90 (d, 3H, J = 2.3 Hz), 2.42 (s, 3H), 3.31 (s, 3H), 5.39 (q, 1H, J = 2.3 Hz), 6.91 (dd, 1H, J = 7.8, 1.7 Hz), 7.06 (td, 1H, J = 7.6, 1.3 Hz), 7.17 (td, 1H, J = 7.7, 1.7 Hz), 7.24 (d, 2H, J = 8.0 Hz), 7.36 (dd, 1H, J = 8.1, 1.3 Hz), 7.45 (d, 2H, J = 8.3 Hz); 13C NMR (100 MHz, CDCl3) δ 8.8, 21.8, 36.7, 63.7, 126.1, 127.1, 127.4, 127.6, 128.8, 130.17, 130.21, 133.6, 134.2, 134.4, 145.4, 159.8, 185.7; IR (neat) (cm-1) 1754s, 1598s, 1587s, 1369s, 1324m, 1304s, 1169s; HRMS (ESI): m/z calcd for C19H18NO3SClNa [M+Na]+: 398.0588; found 398.0592.

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5y: (62.4 mg, 70%); Rf = 0.30 [4:1 petroleum ether/EtOAc]; white solid; mp = 152− −153 oC; 1H NMR (400 MHz, CDCl3) δ 1.74 (d, 3H, J = 2.2 Hz), 2.04 (s, 3H), 2.30 (s, 3H), 2.38 (s, 3H), 4.69 (d, 1H, J = 16.9 Hz), 5.01 (q, 1H, J = 2.2 Hz), 5.12 (d, 1H, J = 16.9 Hz), 6.46 (s, 1H), 6.92 (d, 1H, J = 7.6 Hz), 7.06 (d, 1H, J = 7.7 Hz), 7.13-7.17 (m, 4H), 7.29-7.35 (m, 5H); 13 C NMR (100 MHz, CDCl3) δ 8.7, 19.3, 21.0, 21.7, 53.1, 63.4, 125.9, 126.0, 126.4, 127.6, 128.1, 128.2, 129.0, 129.9, 130.9, 133.95, 133.99, 135.3, 135.4, 136.2, 145.1, 159.7, 187.5; IR (neat) (cm-1) 1748s, 1603s, 1442m, 1372s, 1341s, 1268s, 1165s; HRMS (ESI): m/z calcd for C27H27NO3SNa [M+Na]+: 468.1604; found 468.1608. 5z: (63.9 mg, 62%); Rf = 0.44 [6:1 petroleum ether/EtOAc]; white solid; mp = 116− −117 oC; 1H NMR (400 MHz, CDCl3) δ 0.85 (t, 3H, J = 7.0 Hz), 1.15-1.36 (m, 8H), 2.06 (s, 3H), 2.09-2.13 (m, 2H), 2.35 (s, 3H), 2.37 (s, 3H), 4.76 (d, 1H, J = 17.0 Hz), 5.10 (s, 1H), 5.11 (d, 1H, J = 17.1 Hz), 6.52 (s, 1H), 6.92 (dd, 1H, J = 7.6, 1.8 Hz), 7.06-7.10 (m, 3H), 7.16-7.18 (m, 2H), 7.22-7.25 (m, 2H), 7.29-7.35 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 14.2, 19.4, 21.0, 21.7, 22.7, 24.3, 28.5, 29.4, 31.7, 52.9, 63.4, 126.2, 126.4, 127.6, 128.07, 128.09, 129.0, 129.8, 130.9, 131.2, 134.1, 134.2, 135.26, 135.29, 135.9, 145.0, 158.7, 187.8; IR (neat) (cm-1) 2927m, 1747s, 1593s, 1381m, 1357s, 1321m, 1163s; HRMS (ESI): m/z calcd for C32H37NO3SNa [M+Na]+: 538.2386; found 538.2384. 5': (28.4 mg, 33%); Rf = 0.29 [4:1 petroleum ether/EtOAc]; white solid; mp = 116− −117 oC; 1H NMR (400 MHz, CDCl3) δ 1.38 (d, 3H, J = 2.2 Hz), 2.45 (s, 3H), 3.12-3.23 (m, 2H), 3.97-4.00 (m, 1H), 4.49 (d, 1H, J = 16.8 Hz), 4.90 (d, 1H, J = 16.8 Hz), 6.95-6.96 (m, 2H), 7.20-7.26 (m, 8H), 7.32 (d, 2H, J = 8.2 Hz), 7.67 (d, 2H, J = 8.3 Hz); 13C NMR (100 MHz, CDCl3) δ 7.9, 21.8, 34.6, 52.6, 63.8, 125.0, 126.4, 126.5, 127.5, 127.9, 128.5, 129.0, 129.8, 130.4, 135.4, 135.8, 138.1, 145.4, 162.4, 190.7; IR (neat) (cm-1) 1748s, 1593s, 1386s, 1368s, 1322s, 1169s, 1146s; HRMS (ESI): m/z calcd for C26H25NO3SNa [M+Na]+: 454.1447; found 454.1439. General Procedure for the Synthesis of 4-Amino-2-Napthols. To a sealed tube were added 4-amino-2-napthol derivative 4a (92.0, 0.17 mmol), NaOH (68.8 mg, 1.72 mmol), and methanol (1.72 mL, concn = 0.10 M) under nitrogen atmosphere. The vial was evacuated under vacuum and flushed with nitrogen three times, then sealed under nitrogen and heated to 90 oC, When the reaction was judged to be complete by TLC after 0.5 hours, the reaction mixture was filtered through a pad of silica gel, concentrated in vacuo, and purified by flash silica gel column chromatography [gradient eluent: 8:1~4:1 petroleum ether/EtOAc] to afford 4-amino-2-napthol 6a (63.9 mg, 0.15 mmol) in 89% yield. 6a: (63.9 mg, 89%); Rf = 0.13 [4:1 petroleum ether/EtOAc]; white solid; mp = 177− −178 oC; 1H NMR (400 MHz, CDCl3) δ 1.77 (s, 3H), 2.46 (s, 3H), 4.51 (d, 1H, J = 14.0 Hz), 5.04 (d, 1H, J = 14.0 Hz), 5.53 (s, 1H), 6.95 (s, 1H), 6.97-7.02 (m, 3H), 7.09-7.18 (m, 4H), 7.25-7.29 (m, 3H), 7.48 (d, 1H, J = 8.1 Hz), 7.71-7.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 13.2, 21.8, 55.3, 110.5, 123.7, 123.9, 125.7, 126.8, 126.9, 127.9, 128.2, 128.3, 129.9, 130.2, 131.1, 133.6, 133.7, 135.4, 138.2, 143.7, 152.8; IR (neat) (cm-1) 3481br, 1626w,1349m, 1332m, 1088m; HRMS (ESI): m/z calcd for C25H23NO3SNa [M+Na]+: 440.1291; found 440.1292. 4-Amino-2-napthol 6r was prepared from 4-amino-2-napthol derivative 4r (39.4 mg, 0.06 mmol) and NaOH (22.9 mg, 0.57 mmol) following the general procedure. 6r: (26.6 mg, 82%); Rf = 0.14 [6:1 petroleum ether/EtOAc]; white solid; mp = 165− −166 oC; 1H NMR (400 MHz, CDCl3) δ 1.85 (s, 3H), 2.47 (s, 3H), 4.60 (d, 1H, J = 14.1 Hz), 5.05 (d, 1H, J = 14.1 Hz), 5.16 (s, 1H), 7.02 (t, 1H, J = 7.6 Hz), 7.12 (d, 2H, J = 6.9 Hz), 7.16-7.25 (m, 5H), 7.26-7.32 (m, 3H), 7.39-7.44 (m, 2H), 7.50-7.53 (m, 1H), 7.57-7.61 (m, 2H), 7.74 (d, 2H, J = 8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 13.7, 21.8, 55.5, 121.6, 123.5, 124.2, 125.1, 125.7, 126.9, 127.9, 128.2, 128.3, 128.9, 129.80, 129.84, 129.9, 130.3, 131.32, 131.33, 132.5, 134.2, 135.7, 138.4, 143.6, 149.4; IR (neat) (cm-1) 3516br, 1597w, 1386m, 1340, 1155s; HRMS (ESI): m/z calcd for C31H27NO3SNa [M+Na]+: 516.1604; found 516.1607. 4-Amino-2-napthol 6s was prepared from 4-amino-2-napthol derivative 4s (27.1 mg, 0.07 mmol) and NaOH (27.6 mg, 0.69 mmol) following the general procedure. 6s: (27.1 mg, 81%); Rf = 0.19 [6:1 petroleum ether/EtOAc]; white solid; mp = 174− −175 oC; 1H NMR (400 MHz, CDCl3) δ 0.87 (t, 3H, J = 6.8 Hz), 1.24-1.29 (m, 6H), 1.59-1.65 (m, 2H), 2.61-2.65 (m, 2H), 3.05 (s, 3H), 4.79 (d, 1H, J = 14.3 Hz), 5.00 (d, 1H, J = 14.3 Hz), 5.23 (s, 1H), 7.287.37 (m, 8H), 7.42-7.45 (m, 2H), 7.51-7.55 (m, 1H), 7.59-7.63 (m, 2H), 7.87 (d, 1H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3) δ 14.3, 22.8, 28.8, 29.1, 30.5, 31.7, 42.1, 56.7, 122.2, 124.0, 124.4, 125.4, 126.0, 127.3, 128.5, 128.7, 129.9, 130.0, 130.4, 131.3, 131.5, 134.0, 134.1, 134.7, 135.9, 149.7; IR (neat) (cm-1) 3531br, 1593w, 1333s, 1212m, 1145s, 1114s;


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HRMS (ESI): m/z calcd for C30H33NO3SNa [M+Na]+: 510.2073; found 510.2079. 4-Amino-2-napthol 6t was prepared from 4-amino-2-napthol derivative 4t (43.0 mg, 0.07 mmol) and NaOH (29.1 mg, 0.73 mmol) following the general procedure. 6t: (27.0 mg, 83%); Rf = 0.10 [6:1 petroleum ether/EtOAc]; white solid; mp = 168− −169 oC; 1H NMR (400 MHz, CDCl3) δ 1.27 (t, 3H, J = 7.6 Hz), 1.80 (s, 3H), 2.46 (s, 3H), 3.03 (q, 2H, J = 7.6 Hz), 4.45 (d, 1H, J = 14.0 Hz), 4.84 (s, 1H), 5.10 (d, 1H, J = 14.0 Hz), 6.98-7.05 (m, 3H), 7.11-7.24 (m, 4H), 7.26-7.28 (m, 2H), 7.34-7.38 (m, 1H), 7.67-7.69 (m, 2H), 7.91 (d, 1H, J = 8.5 Hz); 13C NMR (100 MHz, CDCl3) δ 13.5, 14.2, 18.9, 21.8, 55.5, 122.6, 123.3, 123.4, 124.5, 125.6, 127.0, 127.9, 128.1, 128.3, 129.8, 129.9, 130.3, 131.8, 132.1, 135.7, 138.4, 143.6, 149.4; IR (neat) (cm-1) 3493br, 1337w, 1276s, 1261s, 1154m, 1135m; HRMS (ESI): m/z calcd for C27H27NO3SNa [M+Na]+: 468.1604; found 468.1604. 4-Amino-2-napthol 6u was prepared from 4-amino-2-napthol derivative 4u (36.8 mg, 0.07 mmol) and NaOH (25.1 mg, 0.63 mmol) following the general procedure. 6u: (22.8 mg, 83%); Rf = 0.19 [6:1 petroleum ether/EtOAc]; white solid; mp = 166− −167 oC; 1H NMR (400 MHz, CDCl3) δ 0.88 (t, 3H, J = 7.0 Hz), 1.02-1.10 (m, 1H), 1.16-1.33 (m, 8H), 1.53-1.63 (m, 1H), 2.54-2.58 (m, 3H), 2.99 (q, 2H, J = 7.5 Hz), 3.02 (s, 3H), 4.70 (d, 1H, J = 14.2 Hz), 4.97 (d, 1H, J = 14.2 Hz), 5.10 (s, 1H), 7.19-7.24 (m, 3H), 7.24-7.28 (m, 2H), 7.33-7.37 (m, 1H), 7.43-7.47 (m, 1H), 7.83 (d, 1H, J = 7.9 Hz), 7.92 (d, 1H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3) δ 14.1, 14.3, 18.8, 22.8, 28.7, 28.8, 30.5, 31.7, 41.8, 56.5, 122.9, 123.6, 124.2, 124.4, 125.9, 127.5, 128.4, 128.6, 130.3, 132.2, 132.6, 133.7, 135.9, 149.8; IR (neat) (cm-1) 3498br, 2929w, 1324s, 1210m, 1192m, 1133s; HRMS (ESI): m/z calcd for C26H33NO3SNa [M+Na]+: 462.2073; found 462.2074. General Procedure for the Synthesis of 3-Amino-1-Napthols. To an oven-dried sealed tube were added 3-aminocyclobuteneone 5a (45.2 mg, 0.11 mmol), and 1, 4-dioxane (1.0 mL, concn = 0.10 M) under nitrogen atmosphere. The vial was evacuated under vacuum and flushed with nitrogen three times, then sealed under nitrogen and heated to 110 oC. When the reaction was judged to be complete by TLC after 2.0 hours, the mixture was purified using silica gel flash column chromatography [gradient eluent: 6:1~4:1 petroleum ether/EtOAc] to afford 3-amino-1napthol 7a (44.9 mg 0.11 mmol) in 99% yield. 7a: (44.9 mg, 99%); Rf = 0.19 [4:1 petroleum ether/EtOAc]; white solid; mp = 177− −178 oC; 1H NMR (400 MHz, CDCl3) δ 2.04 (s, 3H), 2.47 (s, 3H), 4.27 (d, 1H, J = 13.4 Hz), 5.11 (d, 1H, J = 13.4 Hz), 5.23 (s, 1H), 6.74 (s, 1H), 7.13-7.16 (m, 5H), 7.30 (d, 2H, J = 8.0 Hz), 7.35-7.50 (m, 3H), 7.62 (d, 2H, J = 8.3 Hz), 8.04 (d, 1H, J = 8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 11.5, 21.8, 56.9, 119.0, 119.9, 121.6, 124.0, 126.09, 126.13, 127.4, 128.1, 128.3, 128.4, 129.6, 129.7, 131.9, 135.4, 135.9, 137.4, 143.8, 149.9; IR (neat) (cm-1) 3501br, 1574w, 1496w, 1367m, 1340s, 1266s, 1154s, 1119s; HRMS (ESI): m/z calcd for C25H23NO3SNa [M+Na]+: 440.1291; found 440.1284. 3-Amino-1-napthol 7f was prepared from 3-aminocyclobuteneone 5f (24.6 mg, 0.07 mmol) following the general procedure. 7f: (26.5 mg, 93%); Rf = 0.19 [4:1 petroleum ether/EtOAc]; white solid; mp = 164－165 oC; 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 2.47 (s, 3H), 3.93 (dd, 1H, J = 14.0, 7.7 Hz), 4.42 (dd, 1H, J = 14.0, 5.9 Hz), 4.96 (d, 1H, J = 4.9 Hz), 4.99 (s, 1H), 5.39 (s, 1H), 5.71-5.82 (m, 1H), 6.69 (s, 1H), 7.29 (d, 2H, J = 8.0 Hz), 7.39-7.51 (m, 3H), 7.59 (d, 2H, J = 8.2 Hz), 8.11 (d, 1H, J = 8.3 Hz); 13C NMR (100 MHz, CDCl3) δ 11.8, 21.8, 55.5, 118.7, 119.7, 120.2, 121.5, 124.1, 126.18, 126.20, 127.5, 128.3, 129.6, 131.9, 132.4, 135.9, 137.3, 143.8, 150.1; IR (neat) (cm-1) 3453br, 1573w, 1334s, 1307m, 1287m, 1153s, 1123s; HRMS (ESI): m/z calcd for C21H21NO3SNa [M+Na]+: 390.1134; found 390.1133. 3-Amino-1-napthol 7u was prepared from 3-aminocyclobuteneone 5u (46.3 mg, 0.10 mmol) following the general procedure. 7u: (46.7 mg, 99%); Rf = 0.23 [4:1 petroleum ether/EtOAc]; white solid; mp = 174− −175 oC; 1H NMR (400 MHz, CDCl3) δ 2.07 (s, 3H), 2.48 (s, 3H), 4.19 (d, 1H, J = 13.2 Hz), 5.20 (d, 1H, J = 13.2 Hz), 5.27 (s, 1H), 7.07 (s, 1H), 7.14-7.18 (m, 5H), 7.29-7.35 (m, 3H), 7.44-7.46 (m, 1H), 7.63 (d, 2H, J = 7.9 Hz), 7.99 (d, 1H, J = 8.5 Hz); 13C NMR (100 MHz, CDCl3) δ 11.5, 21.8, 57.2, 116.3, 120.3, 121.0, 125.2, 125.9, 126.4, 128.1, 128.4, 128.5, 129.3, 129.8 (2C), 131.5, 135.2, 135.3, 138.8, 144.1, 150.2, one carbon missing due to overlap; IR (neat) (cm-1) 3514br, 1596s, 1502s, 1494s, 1455s, 1394s, 1341s, 1326s; HRMS (ESI): m/z calcd for C25H22NO3SClNa [M+Na]+: 474.0901; found 474.0897. 3-Amino-1-napthol 7y was prepared from 3-aminocyclobuteneone 5y (41.5 mg, 0.09 mmol) following the general procedure.

7y: (42.1 mg, 99%); Rf = 0.29 [4:1 petroleum ether/EtOAc]; white solid; mp = 56− −57 oC; 1H NMR (400 MHz, CDCl3) δ 2.02 (s, 3H), 2.16 (s, 3H), 2.45 (s, 3H), 2.75 (s, 3H), 3.68 (s, 1H), 4.28 (d, 1H, J = 13.3 Hz), 5.15 (d, 1H, J = 13.3 Hz), 5.32 (s, 1H), 6.70 (s, 1H), 6.97-7.03 (m, 2H), 7.13-7.17 (m, 4H), 7.28 (d, 2H, J = 7.9 Hz), 7.62 (d, 2H, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 11.3, 19.4, 21.7, 25.0, 57.2, 67.2, 116.6, 119.3, 123.6, 126.5, 128.0, 128.4, 128.6, 129.5, 129.7, 131.3, 132.8, 135.5, 135.9, 136.5, 143.7, 153.0; IR (neat) (cm-1) 3496br, 1579s, 1508s, 1456s, 1425s, 1340s, 1324s, 1156s; HRMS (ESI): m/z calcd for C27H27NO3SNa [M+Na]+: 468.1604; found 468.1597.

ASSOCIATED CONTENT Supporting Information The Supporting Information. This material is available free of charge on the ACS Publications website. Spectroscopic data for the new compounds (PDF) Crystallographic data for 4a and 5a (CIF)

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] (X.-N. W.) *E-mail: [email protected] (J. C.) Notes. The authors declare no competing financial interest.

ACKNOWLEDGMENT We thank the National Natural Science Foundation of China (No. 81330075), the China Postdoctoral Science Foundation (Nos. 2015M570631 and 2016T90672), and the Outstanding Young Talent Research Fund of Zhengzhou University (No. 1621331003) for financial support and Professor Richard P. Hsung of the University of Wisconsin–Madison for invaluable discussions.

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Lewis Acids Catalyzed Annulations of Ynamides with Acyl Chlorides

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