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Metal-Free Oxidative Decarbonylative [3+2] Annulation of Terminal Alkynes with Tertiary Alkyl Aldehydes Toward Cyclopentenes Hua-Xu Zou, Yang Li, Xu-Heng Yang, Jiannan Xiang, and Jin-Heng Li J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01130 • Publication Date (Web): 05 Jun 2018 Downloaded from http://pubs.acs.org on June 6, 2018

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The Journal of Organic Chemistry

Metal-Free Oxidative Decarbonylative [3+2] Annulation of Terminal Alkynes with Tertiary Alkyl Aldehydes Toward Cyclopentenes Hua-Xu Zou,†,‡ Yang Li,*†,‡ Xu-Heng Yang,†,‡ Jiannan Xiang† and Jin-Heng Li*,†,‡,§ State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha

†

410082, China Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle,

‡

Nanchang Hangkong University, Nanchang 330063, China State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China

§

[email protected] and [email protected] RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to) H

R4

R4

R1

R1

R1 R3

o

R2

R3

TBHP, PhCl, 100 C OHC

R2

R3 OHC

metal-free oxidative [3+2] annulation

R2

R1

TBHP, PhCl, 100 oC

R2

R3

28 examples, up to 81% yield

Abstract A new metal-free oxidative decarbonylative [3+2] annulation of terminal alkynes with tertiary alkyl aldehydes is presented, which features broad substrate scope and excellent selectivity. The selectivity of this reaction toward cyclopentenes and indenes relies on the nature of the aldehyde

ACS Paragon Plus Environment

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substrates: while treatment of tertiary γ,δ-unsaturated aldehydesd with common terminal alkynes assemble cyclopentenes, 2-methyl-2-arylpropanals succed to access indenes.

Introduction Five-membered carbocycles, including cyclopentenes and indenes, are important structural motifs which widely existed in natural products and pharmaceuticals (Figure 1).1,2 In particular, cyclopentenes and their polycycles, such as carbovir,2a 4-ACPCA,2b gukulenin A/B,2c taiwaniaquinol D,2f and ()-japonicols C,2g exhibit significant biological activities, as well as are versatile intermediates for the synthesis of natural products, bioactive compounds, functional materials and significant chiral ligands.1 Accordingly, construction of such cyclopentene backbones continues to be a major focus of chemical synthesis, and conventional synthetic methodologies are concentrated on reactions that involve intra- or intermolecular annulation processes.1,3,4 Despite impressive advances in the field, efficient intermolecular approaches to selectively access cyclopentene structures, especially structures that own an all-carbon quaternary center, is challenging3 and examples of radical-mediated annulation for such purposes are quite rare.4 Recently, remarkable progress in the oxidative radical catalysis that has been developed for the intramolecular annulation of unsaturated molecules (e.g. alkynes and alkenes) initiated by the alkyl carbon-centered radical systems;5 however, there has been no corresponding

Figure 1. Important molecules containing five-membered carbocycle moieties


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The Journal of Organic Chemistry NH2

N

OH

OH

O

N HO

O

OH

O

NH

N

COOH 4-ACPCA

NH2

Carbovir

H

H

iPr

R

iPr

Ph O OH AcO Gukulenin A (R = CHO) Gukulenin B (R = CH2OH) OH CHO iPr

HO2C HO

HO

H

H

N OH

O

N

O (±) - Japonicols C

(A chemokine receptor modulator)

(Aldosterone synthase inhibitors)

MeO OH Taiwaniaquinol D

success with intermolecular annulation reactions, wherein the intramolecular version is usually preferential. We envisioned that the alkyl carbon-centered radical systems having a radicalaccepted functional group could be used to competitively trap the radical intermediate from their initial reaction with unsaturated molecules and consequently the intramolecular process might be suppressed. Very recently, Tang group4g and our group4h independently developed new strategies, including the classical Cu-catalyzed halogen atom transfer strategy and the Ag-catalyzed oxidative decarboxylation strategy, for the synthesis of cyclopentenes via metal-catalyzed [3+2] annulations of terminal alkynes with unsaturated α‑halogenocarbonyls or tertiary unsaturated acids (eq 1; Scheme 1a). In 2016, we developed a new metal-free radical-mediated oxidative decarbonylative hydroalkylation of terminal and internal alkynes with alkyl aldehydes, including benzyl, secondary and tertiary alkyl aldehydes using di-tert-butyl peroxide (DTBP) oxidant, which enables the simultaneous formation of a C-C bond and a C-H bond through a sequence of decarbonylation, radical addition and protonation (eq 2; Scheme 1b). Subsequently, we have reported a manganese-


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catalyzed intermolecular oxidative acylative annulation of alkynes with -vinyl aldehydes for the divergent synthesis of bridged tricarbocycles, bridged bicyclic and tricyclic carbocycles. This reaction is applicabe to secondary γ,δ-vinyl aldehydes, thus three chemical bonds, including two CC bonds and one C-H bond, are formed via aldehyde C(sp2)-H oxidative functionalization, [4+2] annulation and protonation cascades (eq 3; Scheme 1b). However, Using and a tertiary γ,δ-vinyl aldehyde the reaction proceeded via a decarbonylative [3+2] annulation process. On the basis, aldehydes can undergo decabonylation and acylation selevtively, which rely on the electronic and steric hindrance nature of steraldehyes as well as the oxidative reaction conditions. As a continuous interst in the oxidative tansformations of aldehydes with unsaturated hydrocarbons, we here report a new metal-free oxidative decarbonylative [3+2] annulation of terminal alkynes with tertiary alkyl aldehydes for the synthesis of diverse polysubstituted cyclopentenes. This reaction allows the formation of two C-C bonds through a sequence of decarbonylation6,7, annulation and protonation, and represents the first example of intermolecular [3+2] annulation of terminal alkynes using an oxidative radical-mediated decarbonylation strategy. Furthermore, this reaction could be extended to access indenes involving aryl C(sp2)-H functionalization by designing the substrates (eq 4; Scheme 1c).

Scheme 1. Radical-mediated [3+2] annulation and transformation of aldehydes.


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The Journal of Organic Chemistry a) Previous work: Metal-catalyzed annulation i) Classical halogen atom transfer ii) Oxidative decarboxylation H 2 3 R2 R3 X R R 1 R R1 CO2H n X R1 n CuSO4, bpy, AgNO3, K2S2O8 1 3 3 K2CO3, MeCN, 80 oC H2O/MeCN, 40 oC R2 R R2 R = alkyl n = 1, 2 = ester, ketone R 2, R 3 X = Cl, Br, I R2, R3 b) Our previous work: Oxidative radical transformations of aldehydes R2 DTBP R2 + OHC R3 R1 o MeCN, 110 C, 12 h = 1o (only benzyl), 2o o alkyl R3 R1 R3 ,3 H H (10 mol %) 1 R MnSO4 R1 TBHP (3 equiv) H + R1 R2 + ' PhCF3, Ar, 100 oC, 12 h R2 R O R = aryl, alkyl, TMS, CO O R1 tertiary aldehyde 2Me, CON(Me)Ph secondary = H, Ph, CO 2 (only two examples) R 2Me, CONMe2 aldehydes c) This work: Metal-free oxidative decebonylative annulation R4 R4 R1 Metal-Free + R1 R3 TBHP, PhCl, 100 oC, Ar, 12 h 1 3 2 OHC R R2 R 2 3

(1)

(2)

(3)

(4)

Results and discussion We initiated our investigations of the [3+2] annulation by combining phenylacetylene (1a) with 2,2-dimethylpent-4-enal (2a) in the presence of oxidants (Table 1). After evaluating various reaction parameters, alkyne 1a reacted with 2,2-dimethylpent-4-enal (2a), and 3 equiv of TBHP (tert-butyl hydroperoxide; 5 M in decane) in PhCl at 100 oC for 12 h was preferred and gave the desired cyclopentene 3aa in 74% yield (entry 1). However, the reaction could not occur in the absence of TBHP (entry 2). Other alternative oxidants, such as aqueous TBHP, DTBP (Di-tert-butyl peroxide), TBPB (tert-Butyl peroxybenzoate), CHP (Cumene hydroperoxide) and K2S2O8, displayed reactivity (entries 3-7), but they were inferior to TBHP (5 M in decane). We found that a lower amount of TBHP (2 equiv) had a negative effect (entry 8), and a higher amount of TBHP (4 equiv)


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delivered identical results to those of 3 equiv TBHP (entry 9). A screen of the solvent effect revealed that the use of CH2ClCH2Cl resulted in no formation of 3aa (entry 10), and two other solvents, including MeCN and DMF, exhibited less efficient than PhCl (entries 11 and 12). Among the reaction temperature effect examined, the reaction at 100 oC was turned out to be taken precedence over either 110 oC or 90 oC (entry 1 versus entries 13 and 14). It is noteworthy that the reaction is applicable to 1 mmol scale of alkyne 2a, accessing 3aa in good yield (entry 15).

Table 1. Screening of the reaction conditionsa Ph

TBHP (3 equiv)

+

Ph

o

PhCl, 100 C, Ar, 12 h 1a

OHC 2a

3aa

Entry

variation from the standard conditions

Yield [%]b

1 2 3 4 5

none without TBHP TBHP (70% in H2O) DTBP instead of TBHP TBPB instead of TBHP

74 0 26 48 36

51 6 CHP instead of TBHP 14 7 K2S2O8 instead of TBHP 52 8 TBHP (2 equiv) 9 TBHP (4 equiv) 72 10 CH2ClCH2Cl instead of PhCl trace 11 MeCN instead of PhCl 62 12 DMF instead of PhCl 49 o 13 110 C 73 o 14 90 C 58 15b none 70 a Reaction conditions: 1a (0.2 mmol), 2a (2 equiv), TBHP (5 M in decane; 3 equiv), PhCl (2 mL), argon, 100 oC and 12 h. b 1a (1 mmol), PhCl (5 mL) and 36 h.


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Having established the optimal reaction conditions, we turned our attention to exploit the scope of this [3+2] annulation with regard to alkynes 1 and aldehydes 2 (Table 2, Scheme 2 and Scheme 3). In the presence of 2,2-dimethylpent-4-enal (2a), a wide range of electron-rich and electrondeficient terminal alkynes 1b-p were found to be compatible with the optimal conditions (3ba-pa; Table 2). For aryl alkynes 1b-h, various substituents, including Me, MeO, Br and Cl, on the aryl moiety were well tolerated (3ba-ha). It was noted that the substitution electronic nature had a fundamental influence on the reactivity, but the substitution position showed slight effect. While aryl alkyne 1b having an electron-donating p-Me group delivered 3ba in 81% yield, aryl alkyne 1d with a weak electron-withdrawing position were converted into 3ea-ga, respectively, in 66% yield. It was noted that 1-ethynylnaphthalene 1i was transformed into 7,7a,8,9-tetrahydrocyclopenta[a]phenalene (3ia), a cyclopentene-fused polycycle, via oxidative decarbonylation, annulation, protonation and C-H functionalization cascades. Heteroaryl alkynes 1j-k were both viable for giving 3ja-ka in good yields. Two functionalized alkynes, including vinyl alkyne 1l and 1,3-diyne 1m, were viable to furnish functionalized cyclopentenes 3la and 3ma, which made this [3+2] annulation more attractive. Unfortunately, aliphatic alkyne 1n had no reactivity (3na). For electron-deficient alkynes, namely 1-phenylprop-2-yn-1-one 1o, benzyl propiolate 1s and Nmethyl-N-phenylpropiolamide 1p, were suitable substrates (3oa-pa). Notably, propiolamide 1p gave 3pa in moderate yield along with an inherent C-H functionalization product 4pa. It was noted that internal alkyne 1q was not a suitable substrate (3qa). The feasibility of the [3+2] annulation with other alkyl aldehydes 2b-g was next investigated (3ab-ad, 3je, and 3af-ag). Using tertiary alkyl aldehydes, such as 2,2-diethylpent-4-enal (2b), 2ethyl-2-methylpent-4-enal (2c), 2,2-diethylhex-4-enal 2d and 2-methyl-2-phenylpent-4-enal 2e,


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react with alkynes 1a or 1j efficiently, affording the corresponding products 3ab-3ad and 3je in moderate yields. However, secondary alkyl aldehyde 1f was inert and could be recovered (3af). Furthermore, attempt to build six-membered ring from 2,2-dimethylhex-5-enal (2g) was failed (3ag).

Table 2. Variations of the terminal alkynes (1) and -vinyl alkyl aldehydes (2)a

R4

R4

H TBHP

+

R1 1

R3 OHC

Ph

o

PhCl, 100 C, Ar, 12 h

R2 2


3 R2 R 3

8

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The Journal of Organic Chemistry Br

MeO

H

Cl H

H

3ba, 81%

3ca, 68% H

H

3da, 60% MeO

H

3ea, 72% H

Cl Cl

MeO

3ga, 78% S

3fa, 70% H

3ha, 66% H

3ia, 46% Ph

H

H

N

3ja, 72% H

3ka, 65% O

H

O

Ph

3na, trace

+

N O 4pa, 21%

3pa, 47%

H

H

H

N Ph

3oa, 46%

H

Ph

Ph

3ma, 41%

3la, 57%

H

Ph

Ph

Ph 3qa, trace

3ab, 58%

3ac, 65% (d.r. = 1:1)

H

H Ph

N

3ad, 51% H Ph

Ph

3je, 37% (d.r. = 1:1)

3af, trace

3ag, trace

Reaction conditions: 1 (0.2 mmol), 2 (2 equiv), TBHP (5 M in decane; 3 equiv), PhCl (2 mL), argon, 100 oC and 12 h. a

Importantly, this reaction was applicable to 2-methyl-2-phenylpropanal (2h). In the presence of TBHP, 2-methyl-2-phenylpropanal (2h) could smoothly undergo the [3+2] annulation through C-H functionalization to assemble indenes 3jh and 3ph. However, secondary 2-phenylpropanal 2i failed to execute the reaction under the optimal conditions (3ji).


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Scheme 2. The decarbonylation annulation with 2-phenylpropanals (2) R4 +

R1 1

TBHP H

R3

OHC

Ph

o

PhCl, 100 C, Ar, 12 h

R2

3 R2 R 3

2 O Ph

N

3jh, 52%

N

3ph, 51% (d.r. = 2:1)

N

3ji, trace

As shown in Scheme 3, treatment of alkyne 1a with pivalaldehyde 2j and TBHP afforded the hydroalkylation product 5aj in 70% yield (eq 5).6j For 2-phenylacetaldehyde 2k, a primary aldehyde, decarbonylative hydroalkylation of 4-ethynyltoluene (1b) also occurred, offering the alkene 5bk in 40% yield (eq 6). However, the reaction of alkyne 1a with aldehyde 2a was inhibited when a stoichiometric amount of radical inhibitors, including TEMPO, hydroquinone and 2,6-di-

tert-butyl-4-methylphenol (BHT), was added (eq 7). These results suggest that this [3+2] annulation reaction involves a free-radical process. To further understand the mechanism, the deuterium labeling experiments were performed (eqs 8 and 9). In the presence of D2O, a number of deuterium atoms were incorporated into the resulting product 3aa (eq 8). However, no deuterium-labelled product was observed when using CD3CN as the medium (eq 9).

Scheme 3. Other aldehydes and control experiments


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+

Ph 1a

Ph

PhCl, 100 C, Ar, 12 h

OHC 2a

(5) Ph 5aj, 70% H

TBHP (3 equiv) + OHC CH Ph o 2 PhCl, 100 C, Ar, 12 h 2k

Ph

TBHP (3 equiv) o PhCl, 100 C, Ar, 12 h

Ph (7) 3aa, trace

Additive = TEMPO, hydroquinone, 2,6-di-tert-butyl-4-methylphenol (BHT) H(D) 0.36 D Ph Ph D2O (0.1 mL) + TBHP (3 equiv) o OHC PhCl, 100 C, Ar, 12 h 1a 2a 3aa, 71% H(D) Ph

TBHP (3 equiv)

+ 1a

Ph

(8)

only H (9)

o

OHC 2a

(6)

5bk, 40% Additive (2 equiv)

+

H

o

2j

1b

1a

TBHP (3 equiv)

OHC

CD3CN, 100 C, Ar, 12 h 3aa, 62%

The mechanism for this [3+2] annulation reaction was proposed (Scheme 4).4-6 In the presence of peroxide, aldehyde 2a is easily transformed into the carbonyl radical A under heating conditions,5,6 which sequentially undergoes decarbonylation to afford the alkyl radical intermediate B. Intermolecular addition of the intermediate B across the C≡C bond of the alkyne 1a selectively generates the vinyl radical intermediate C, followed by rapidly annulation with the C=C bond in the aldehyde 2a gives the new alkyl radical intermediate D. Finally, protonation of the intermediate D assembles the desired product 3aa.


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Scheme 4. Possible Mechanism.

t-BuOOH H

+

t-BuO t-BuO +

OH

OH

O

O CO

t-BuOH + H2O

2a

Ph H2O, t-BuOH, t-BuOOH or/and 2a

Ph

B

A

Ph

1a

Ph

2t-BuOO and/or A 3aa

D

C

Conclusions In summary, we have developed a novel oxidative decarbonylative [3+2] annulation of terminal alkynes with tertiary alkyl aldehyde for the synthesis of polysubstituted cyclopentenes and indenes. This reaction enables the formation of two new C-C bonds using a metal-free oxidative decarbonylation strategy, and represents a new oxidative radical-mediated intermolecular [3+2] annulation of alkynes with alkyl radicals that are formed from decarbonylation of tertiary alkyl aldehydes having an aldehyde group connected to the tertiary sp3-hybridized carbon atom. Importantly, selectivity toward cyclopentenes and indenes is controllable and relies on the nature of substrates, which makes this type of transformation useful in synthetic and medicinal chemistry.

Experimental Section General Considerations: The 1H and 13C NMR spectra were recorded in CDCl3 solvent on a NMR spectrometer using TMS as


12

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internal standard. HRMS was measured on an electrospray ionization (ESI) apparatus using time-offlight (TOF) mass spectrometry. Melting points are uncorrected.

Typical Experimental Procedure for the Synthesis of Tertiary Alkyl Aldehydes (2):8 To a solution of aldehyde (10 mmol) in CH2Cl2 (50 mL) was added in one portion KOtBu (13 mmol), followed immediately by allylbromide (20 mmol). The resulting mixture was stirred for 2h at room temperature, and then water (20 mL) was added. The organic layer was further washed with water (3×10 mL), dried over MgSO4, filtered, and concentrated in vacuum. The resulting residue was purified by flash column chromatography using petroleum ether/Et2O (9:1) eluent to give the title compound 2. Typical Experimental Procedure for Decarbonylative Annulation of Terminal Alkynes with Tertiary Alkyl Aldehydes Toward Cyclopentenes: To a Schlenk tube were added alkyne 1 (0.2 mmol), aldehyde 2 (2 equiv), TBHP (5 M in decane; 3 equiv), and PhCl (2 mL). Then the tube was charged with argon, and was stirred at 100 oC (oil bath temperature) under argon atmosphere for the indicated time until complete consumption of starting material as monitored by TLC and/or GC-MS analysis. After the reaction was finished, the reaction mixture was cooled to room temperature, diluted in diethyl ether, and washed with brine. The aqueous phase was re-extracted with EtOAc (3×10 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuum. The resulting residue was purified by silica gel flash column chromatography (hexane/ethyl acetate = 50:1) to afford the desired product 3.

(3,3,5-Trimethylcyclopent-1-en-1-yl)benzene (3aa): 27.5 mg, 74%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.37 (d, J = 7.6 Hz, 2H), 7.30 (t, J = 7.2 Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H), 5.79 (s, 1H), 3.31 (dd, J = 13.2, 6.8 Hz, 1H), 2.12 (dd, J = 11.2, 10.0 Hz, 1H), 1.47 (dd, J = 12.8, 4.8 Hz, 1H), 1.18 (s, 3H), 1.12 (d, J = 6.8 Hz, 3H), 1.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.8, 137.4, 136.9, 128.4 (2C), 126.8, 126.5 (2C), 48.2, 44.3, 39.4, 30.3, 29.4, 21.4; LRMS (EI, 70 eV) m/z (%): 186 (M+, 19), ACS Paragon Plus Environment

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171 (100), 91 (17); HRMS m/z (ESI) calcd for C14H19 ([M+H]+) 187.1481, found 187.1488. 1-Methyl-4-(3,3,5-trimethylcyclopent-1-en-1-yl)benzene (3ba): 32.4 mg, 81%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.27 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 7.2 Hz, 2H), 5.74 (s, 1H), 3.29 (dd, J = 12.8, 6.4 Hz, 1H), 2.33 (s, 3H), 2.14-2.08 (m, 1H), 1.47 (dd, J = 12.4, 4.0 Hz, 1H), 1.17 (s, 3H), 1.12 (d, J = 7.2 Hz, 3H), 1.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 144.6, 136.5, 136.5, 134.0, 129.1 (2C), 126.4 (2C), 48.2, 44.2, 39.4, 30.4, 29.5, 21.4, 21.3; LRMS (EI, 70 eV) m/z (%): 200 (M+, 21), 185 (100), 143 (19); HRMS m/z (ESI) calcd for C15H21 ([M+H]+) 201.1638, found 201.1642. 5-(4-Methoxyphenyl)-1,2-diphenylpentane-1,5-dione (3ca): 29.4 mg, 68%; Colorless oil; 1H NMR (500 MHz, CDCl3) δ: 7.30 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 5.68 (s, 1H), 3.80 (s, 3H), 3.26 (d, J = 5.6 Hz, 1H), 2.10 (dd, J = 12.4, 8.8 Hz, 1H), 1.47 (dd, J = 12.8, 4.4 Hz, 1H), 1.17 (s, 3H), 1.11 (d, J = 6.7 Hz, 3H), 1.09 (s, 3H);

13C

NMR (125 MHz, CDCl3) δ: 158.5, 144.1, 135.4, 129.4, 127.5

(2C), 113.7 (2C), 55.3, 48.1, 44.1, 39.4, 30.3, 29.5, 21.4; LRMS (EI, 70 eV) m/z (%): 216 (M+, 18), 201 (100), 172 (10); HRMS m/z (ESI) calcd for C15H21O ([M+H]+) 217.1587, found 217.1592. 1-Bromo-4-(3,3,5-trimethylcyclopent-1-en-1-yl)benzene (3da): 31.7 mg, 60%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.42 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 5.79 (s, 1H), 3.26 (dd, J = 12.4, 6.0 Hz, 1H), 2.15-2.09 (m, 1H), 1.47 (dd, J = 12.8, 4.8 Hz, 1H), 1.18 (s, 3H), 1.09 (d, J = 2.4 Hz, 6H); 13C

NMR (100 MHz, CDCl3) δ: 143.8, 138.2, 135.8, 131.4 (2C), 128.1 (2C), 120.5, 48.1, 44.4, 39.3,

30.2, 29.3, 21.2; LRMS (EI, 70 eV) m/z (%): 266 (M++2, 16), 264 (M+, 16), 251 (82), 170 (100); HRMS m/z (ESI) calcd for C14H18Br ([M+H]+) 265.0586, found 265.0588. 1-Chloro-4-(3,3,5-trimethylcyclopent-1-en-1-yl)benzene (3ea): 31.7 mg, 72%; d Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.27 (d, J = 5.6 Hz, 4H), 5.77 (s, 1H), 3.26 (dd, J = 12.8, 6.4 Hz, 1H), 2.14-2.09 (m, 1H), 1.47 (dd, J = 12.8, 3.2 Hz, 1H), 1.17 (s, 3H), 1.09 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 143.8, 138.0, 135.3, 132.4, 128.5 (2C), 127.8 (2C), 48.2, 44.4, 39.4, 30.2, 29.4, 21.2; LRMS (EI, 70 eV)


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m/z (%): 222 (M++2, 17), 220 (M+, 52), 176 (21), 105 (100); HRMS m/z (ESI) calcd for C14H18Cl ([M+H]+) 221.1092, found 221.1095. 1-Chloro-3-(3,3,5-trimethylcyclopent-1-en-1-yl)benzene (3fa): 30.8 mg, 70%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.34 (s, 1H), 7.23 (d, J = 4.4 Hz, 1H), 7.18 (dd, J = 6.0, 3.2 Hz, 1H), 5.81 (s, 1H), 3.31-3.22 (m, 1H), 2.12 (dd, J = 12.8, 8.4 Hz, 1H), 1.47 (dd, J = 12.8, 5.2 Hz, 1H), 1.18 (s, 3H), 1.10 (d, J = 7.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 143.6, 138.7, 134.1, 129.4, 126.6, 126.5, 124.5, 48.0, 44.2, 39.3, 30.0, 29.2, 21.1; LRMS (EI, 70 eV) m/z (%): 222 (M++2, 7), 220 (M+, 23), 205 (100); HRMS m/z (ESI) calcd for C14H18Cl ([M+H]+) 221.1092, found 221.1095. 1-Chloro-2-(3,3,5-trimethylcyclopent-1-en-1-yl)benzene (3ga): 34.3 mg, 78%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 7.2 Hz, 1H), 7.18-7.13 (m, 3H), 5.60 (s, 1H), 3.48-3.40 (m, 1H), 2.08 (dd, J = 12.4, 8.0 Hz, 1H), 1.39 (dd, J = 12.4, 7.6 Hz, 1H), 1.19 (s, 3H), 1.11 (s, 3H), 0.92 (d, J = 6.8 Hz, 3H)); 13C NMR (100 MHz, CDCl3) δ: 144.0, 141.1, 137.1, 132.5, 130.7, 129.6, 127.8, 126.2, 48.6, 44.3, 41.0, 29.7, 28.1, 20.0; LRMS (EI, 70 eV) m/z (%): 222 (M++2, 7), 220 (M+, 21), 205 (100); HRMS m/z (ESI) calcd for C14H18Cl ([M+H]+) 221.1092, found 221.1095. 2,4-Dimethoxy-1-(3,3,5-trimethylcyclopent-1-en-1-yl)benzene (3ha): 32.5 mg, 66%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.13 (d, J = 8.8 Hz, 1H), 6.44 (d, J = 6.8 Hz, 2H), 5.72 (s, 1H), 3.80 (s, 6H), 3.43 -3.34 (m, 1H), 2.03 (dd, J = 12.4, 8.0 Hz, 1H), 1.36 (dd, J = 12.4, 6.8 Hz, 1H), 1.17 (s, 3H), 1.08 (s, 3H), 0.97 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.6, 158.2, 142.7, 138.4, 130.1, 119.4, 104.0, 98.8, 55.3, 48.2, 43.9, 40.5, 30.1, 28.9, 20.8; LRMS (EI, 70 eV) m/z (%): 246 (M+, 24), 231 (100), 93 (11); HRMS m/z (ESI) calcd for C16H23O2 ([M+H]+) 247.1693, found 247.1699. 9,9-Dimethyl-7,7a,8,9-tetrahydrocyclopenta[a]phenalene (3ia): 21.5 mg, 46%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.73-7.65 (m, 3H), 7.43 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.23 (s, 1H), 6.10 (s, 1H), 3.34 (dd, J = 14.8, 5.6 Hz, 1H), 3.28-3.22 (m, 1H), 2.81 (t, J = 13.6 Hz, 1H), 2.22 (dd,


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J = 12.4, 7.2 Hz, 1H), 1.57-1.52 (m, 2H), 1.26 (s, 3H), 1.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 139.4, 135.9, 133.7, 133.3, 130.6, 129.2, 127.3, 126.0, 125.6, 125.5, 124.3, 120.9, 47.5, 44.9, 41.8, 39.1, 29.9, 28.0; LRMS (EI, 70 eV) m/z (%): 234 (M+, 28), 219 (100), 101 (10); HRMS m/z (ESI) calcd for C18H19 ([M+H]+) 235.1481, found 235.1484. 3-(3,3,5-Trimethylcyclopent-1-en-1-yl)pyridine (3ja): 26.9 mg, 72%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 8.63 (s, 1H), 8.44 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.27-7.21 (m, 1H), 5.87 (s, 1H), 3.31 (dd, J = 13.6, 6.8 Hz, 1H), 2.14 (dd, J = 12.8, 8.4 Hz, 1H), 1.51-1.48 (m, 1H), 1.19 (s, 3H), 1.11 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 147.7, 147.6, 141.6, 139.1, 133.4, 132.3, 123.1,47.9, 44.3, 39.1, 29.9, 29.0, 20.8; LRMS (EI, 70 eV) m/z (%):187 (M+, 18), 172 (100), 144 (11); HRMS m/z (ESI) calcd for C13H18N ([M+H]+) 188.1434, found 188.1439. 3-(3,3,5-trimethylcyclopent-1-en-1-yl)thiophene (3ka): 25.0 mg, 65%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.24 (t, J = 4.0 Hz, 1H), 7.18 (d, J = 4.8 Hz, 1H), 7.09 (s, 1H), 5.73 (s, 1H), 3.21-3.13 (m, 1H), 2.09 (dd, J = 12.8, 8.8 Hz, 1H), 1.47 (dd, J = 12.8, 4.4 Hz, 1H), 1.20 (d, J = 7.2 Hz, 3H), 1.18 (s, 3H), 1.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 139.8, 138.2, 136.3, 126.5, 125.1, 119.8, 48.0, 44.1, 40.2, 30.2, 29.6, 21.7; LRMS (EI, 70 eV) m/z (%):192 (M+, 26), 177 (100), 143 (36); HRMS m/z (ESI) calcd for C12H17S ([M+H]+) 193.1045, found 193.1047. 1-(3,3,5-Trimethylcyclopent-1-en-1-yl)cyclohex-1-ene (3la): 21.7 mg, 57%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 5.71 (s, 1H), 5.36 (s, 1H), 3.01-2.96 (m, 1H), 2.27-2.21 (m, 1H), 2.14-2.06 (m， 3H), 1.98 (dd, J = 12.8, 9.2 Hz, 1H), 1.70 -1.64 (m, 2H), 1.62-1.55 (m, 2H), 1.40 (dd, J = 12.8, 2.8 Hz, 1H), 1.14 (d, J = 7.2 Hz, 3H), 1.12 (s, 3H), 1.04 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 146.2, 133.9, 132.5, 124.5, 47.7, 43.9, 38.7, 30.4, 30.3, 26.5, 25.7, 22.9, 22.5, 22.4; LRMS (EI, 70 eV) m/z (%): 190 (M+, 30), 175 (100), 133 (20); HRMS m/z (ESI) calcd for C14H23 ([M+H]+) 191.1794, found 191.1798. ((3,3,5-Trimethylcyclopent-1-en-1-yl)ethynyl)benzene (3ma): 17.2 mg, 41%; Yellow oil; 1H NMR


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(400 MHz, CDCl3) δ: 7.45 -7.43 (m, 2H), 7.30 (d, J = 5.6 Hz, 3H), 5.92 (s, 1H), 2.04-1.98 (m, 1H), 2.01 (dd, J = 12.4, 4.0 Hz, 1H), 1.35-1.30 (dd, J = 12.8, 7.6 Hz, 1H), 1.21 (d, J = 6.8 Hz, 3H), 1.14 (s, 3H), 1.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 147.4, 131.5 (2C), 128.2 (2C), 127.9, 127.3, 123.6, 91.2, 86.1, 47.9, 44.9, 42.1, 29.5, 27.8, 20.2; LRMS (EI, 70 eV) m/z (%): 210 (M+, 45), 195 (100), 151 (13); HRMS m/z (ESI) calcd for C16H19 ([M+H]+) 211.1481, found 211.1487. Phenyl(3,3,5-trimethylcyclopent-1-en-1-yl)methanone (3oa): 19.7 mg, 46%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.76 (d, J = 7.2 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 6.17 (s, 1H), 3.38-3.30 (m, 1H), 2.10 (dd, J = 12.8, 8.0 Hz, 1H), 1.44 (dd, J = 12.8, 7.2 Hz, 1H), 1.25 (s, 3H), 1.20 (d, J = 6.8 Hz, 3H), 1.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 195.0, 154.8, 145.2, 139.1, 132.0, 129.0 (2C), 128.2 (2C), 47.4, 45.4, 39.2, 29.2, 27.6, 20.1; LRMS (EI, 70 eV) m/z (%): 214 (M+, 26), 105 (100), 77 (42) ; HRMS m/z (ESI) calcd for C15H19O ([M+H]+) 215.1430, found 215.1427. N,3,3,5-tetramethyl-N-phenylcyclopent-1-ene-1-carboxamide (3pa): 22.8 mg, 47%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.33 (t, J = 7.6 Hz, 2H), 7.27 (s, 1H), 7.15 (d, J = 7.6 Hz, 2H), 5.43 (s, 1H), 3.35 (s, 3H), 2.56-2.51 (m, 1H), 1.74 (dd, J = 12.4, 7.6 Hz, 1H), 1.12 (dd, J = 12.0, 8.0 Hz, 1H), 1.04 (d, J = 6.8 Hz, 3H), 0.90 (s, 3H), 0.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 168.8, 145.9, 144.4, 141.0, 129.0 (2C), 127.1 (2C), 126.9, 47.6, 44.5, 39.9, 37.4, 28.7, 26.7, 19.7; LRMS (EI, 70 eV) m/z (%): 243 (M+, 19), 137 (100), 77 (13); HRMS m/z (ESI) calcd for C16H22NO ([M+H]+) 244.1696, found 244.1701. 2,2,5-Trimethyl-2,5,10,10a-tetrahydrobenzo[b]cyclopenta[e]azepin-4(1H)-one (4pa): 10.1 mg, 21%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.27-7.24 (m, 1H), 7.11 (t, J = 4.2 Hz, 3H), 5.65 (d, J = 1.6 Hz, 1H), 3.71 (dd, J = 15.2, 7.2 Hz, 1H), 3.37 (s, 3H), 3.21 (dd, J = 13.6, 6.4 Hz, 1H), 2.39 (d, J = 13.6 Hz, 1H), 1.79 (dd, J = 12.0, 7.2 Hz, 1H), 1.36 (t, J = 13.2 Hz, 1H), 1.03 (s, 3H), 0.81 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 169.2, 143.7, 142.7, 138.8, 133.4, 130.7, 127.3, 125.3, 122.4, 49.9, 44.6, 44.1,


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35.3, 34.3, 28.8, 26.0; LRMS (EI, 70 eV) m/z (%): 241 (M+, 100), 199 (23), 132 (12); HRMS m/z (ESI) calcd for C16H20NO ([M+H]+) 242.1539, found 242.1542. (3,3-Diethyl-5-methylcyclopent-1-en-1-yl)benzene (3ab): 24.8 mg, 58%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.36 (d, J = 8.0 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H), 5.73 (s, 1H), 3.31-3.22 (m, 1H), 2.08 (dd, J = 13.2, 8.8 Hz, 1H), 1.51-1.37 (m, 5H), 1.09 (d, J = 6.8 Hz, 3H), 0.88 (t, J = 7.6 Hz, 3H), 0.82 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 146.1, 137.0, 134.6, 128.2 (2C), 126.6, 126.4 (2C), 51.6, 42.7, 39.2, 32.3, 31.8, 21.2, 9.3, 9.0; LRMS (EI, 70 eV) m/z (%): 214 (M+, 4), 185 (100), 143 (14); HRMS m/z (ESI) calcd for C16H23 ([M+H]+) 215.1794, found 215.1799. (3-Ethyl-3,5-dimethylcyclopent-1-en-1-yl)benzene (3ac): 26.0 mg, 65%; d.r. = 1:1; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.37 (t, J = 7.2 Hz, 2.1H), 7.30 (t, J = 7.6 Hz, 2.1H), 7.20 (t, J = 7.2 Hz, 1.0H), 5.77 (s, 1H), 3.35-3.24 (m, 1.0H), 2.19 (dd, J = 12.8, 8.8 Hz, 0.5H), 2.01 (dd, J = 12.8, 8.4 Hz, 0.5H), 1.54-1.33 (m, 3.5H), 1.13 (d, J = 6.0 Hz, 2.1H), 1.10 (d, J = 7.2 Hz, 2.1H), 1.05 (s, 1.5H), 0.91 (t, J = 7.6 Hz, 1.6H), 0.85 (t, J = 7.6 Hz, 1.6H); 13C NMR (100 MHz, CDCl3) δ: 145.4, 145.2, 137.0, 136.8, 136.3, 135.7, 128.2 (3C), 126.6, 126.4 (2C), 47.9, 47.8, 45.5, 39.4, 38.7, 34.9, 34.8, 27.8, 26.3, 21.5, 20.9, 9.6, 9.4; LRMS (EI, 70 eV) m/z (%): 200 (M+, 6), 171 (100), 143 (22); HRMS m/z (ESI) calcd for C15H21 ([M+H]+) 201.1638, found 201.1642. (3,3,5-Triethylcyclopent-1-en-1-yl)benzene (3ad): 23.3 mg, 51%; Colorless oil; 1H NMR (400 MHz, CDCl3) δ: 7.35-7.30 (m, 4H), 7.20 (t, J = 6.8 Hz, 1H), 5.71 (s, 1H), 3.11 (d, J = 8.0 Hz, 1H), 1.98 (dd, J = 13.2, 8.8 Hz, 1H), 1.74-1.72 (m, 1H), 1.52-1.35 (m, 5H), 1.19-1.09 (m, 1H), 0.90-0.80 (m, 9H); 13C NMR (100 MHz, CDCl3) δ: 145.3, 137.4, 135.2, 128.1 (2C), 126.6, 126.4 (2C), 51.5, 46.4, 39.4, 32.3, 31.9, 27.5, 11.8, 9.3, 9.0; LRMS (EI, 70 eV) m/z (%): 228 (M+, 4), 199 (100), 143 (14); HRMS m/z (ESI) calcd for C17H25 ([M+H]+) 229.1951, found 229.1954. 3-(3,5-Dimethyl-3-phenylcyclopent-1-en-1-yl)pyridine (3je): 18.4 mg, 37%; d.r. = 1:1; Yellow oil; 1H


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NMR (400 MHz, CDCl3) δ: 8.70 (s, 1.0H), 8.49 (d, J = 4.0 Hz, 1.0H), 7.71 (d, J = 7.6 Hz, 1.0H), 7.39 (d, J = 8.0 Hz, 1.0H), 7.37-7.26 (m, 4.2H), 7.23-7.16 (m, 1.0H), 6.20 (s, 0.5H), 6.17 (s, 0.5H), 3.44-3.33 (m, 1.0H), 2.61 (dd, J = 13.2, 8.8 Hz, 0.5H), 2.49 (dd, J = 12.8, 8.0 Hz, 0.5H), 1.94 (dd, J = 12.8, 6.0 Hz, 0.5H), 1.85 (dd, J = 13.2, 5.2 Hz, 0.5H), 1.60 (s, 1.5H), 1.49 (s, 1.5H), 1.18 (d, J = 6.8 Hz, 1.5H), 1.05 (d, J = 6.8 Hz, 1.5H); 13C NMR (100 MHz, CDCl3) δ: 150.3, 149.8, 148.1, 148.0, 147.9, 146.5, 143.6, 136.8, 136.6, 133.7, 128.3, 128.3, 125.9, 125.8, 125.7, 123.2, 51.8, 51.5, 49.8, 49.8, 39.4, 39.0, 29.8, 28.5, 20.8, 19.9; LRMS (EI, 70 eV) m/z (%): 249 (M+, 16), 211 (M+, 27), 173 (100); HRMS m/z (ESI) calcd for C18H20N ([M+H]+) 250.1590, found 250.1597. 3-(1,1-Dimethyl-1H-inden-3-yl)pyridine (3jh): 23.0 mg, 52%; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 8.85 (s, 1H), 8.60 (d, J = 4.4 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.45-7.37 (m, 3H), 7.30-7.28 (m, 2H), 6.49 (s, 1H), 1.41 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 13C NMR (101 MHz, CDCl3) δ 154.2, 148.8, 148.7, 145.4, 141.0, 137.7, 134.8, 131.6, 126.5, 125.8, 123.4, 121.7, 120.2, 48.8, 24.6.; LRMS (EI, 70 eV) m/z (%): 221 (M+, 13), 177 (15), 143 (100); HRMS m/z (ESI) calcd for C16H16N ([M+H]+) 222.1277, found 222.1281. N,1,1-trimethyl-N-phenyl-1H-indene-3-carboxamide (3ph): 28.3 mg, 51%; d.r. = 2:1; Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.42 (t, J = 7.6 Hz, 3.0H), 7.32-7.17 (m, 4.5H), 7.09 (t, J = 7.6 Hz, 0.3H), 7.00 (t, J = 7.6 Hz, 0.7H), 6.75-6.69 (m, 1.0H), 6.58 (t, J = 7.6 Hz, 0.3H), 6.21 (d, J = 7.6 Hz, 0.3H), 3.23 (s, 1.0H), 3.13 (s, 2.0H), 1.79 (s, 4.0H), 1.65 (s, 2.1H); 13C NMR (100 MHz, CDCl3) δ: 13C NMR (101 MHz, CDCl3) δ 164.9, 164.8, 150.9, 150.8, 149.9, 149.8, 147.7, 142.5, 128.8, 128.7, 128.7, 128.0, 127.4, 127.1, 126.3, 126.0 (2C), 125.9, 125.8, 123.8, 121.6, 120.5, 119.8, 118.7, 107.7, 107.6, 41.3, 41.2, 30.5, 29.2, 26.1, 25.8.; LRMS (EI, 70 eV) m/z (%): 277 (M+, 27), 219 (100), 175 (18); HRMS m/z (ESI) calcd for C19H20NO ([M+H]+) 278.1539, found 278.1543. (3,3-Dimethylbut-1-en-1-yl)benzene (5aj): 22.4 mg, 70%; d.r. = 1.25:1; Colorless liquid; 1H NMR (400 MHz, CDCl3) δ: 7.37-7.35 (m, 1.0H), 7.31-7.23 (m, 2.1H), 7.22-7.17 (m, 2.1H), 6.41 (d, J = 12.8 ACS Paragon Plus Environment

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Hz, 0.5H), 6.29 (s, 0.5H), 6.27 (s, 0.4H), 5.60 (d, J = 12.4 Hz, 0.5H), 1.12 (s, 4.2H), 0.98 (s, 5H); 13C NMR (100 MHz, CDCl3) δ: 142.6, 141.8, 139.4, 138.0, 128.9, 128.5, 127.5, 127.1, 126.7, 126.1, 126.0, 124.5 (2C), 34.2, 33.3, 31.2, 29.6; LRMS (EI, 70 eV) m/z (%): 160 (M+, 30), 145 (100), 117 (31); HRMS m/z (ESI) calcd for C12H17 ([M+H]+) 161.1325, found 161.1331. 1-Methyl-4-(3-phenylprop-1-en-1-yl)benzene (5bk): 16.6 mg, 40%; d.r. = 2:1; Colorless liquid; 1H NMR (400 MHz, CDCl3) δ: 7.32-7.09 (m, 9.7H), 6.56 (d, J = 11.2 Hz, 0.6H), 6.43 (d, J = 16.0 Hz, 0.3H), 6.34-6.28 (m, 0.3H), 5.85-5.78 (m, 0.6H), 3.69 (d, J = 7.6 Hz, 1.3H), 3.54 (d, J = 6.4 Hz, 0.6H), 2.35 (s, 2.0H), 2.32 (s, 0.9H); 13C NMR (100 MHz, CDCl3) δ: 141.8, 140.9, 136.5, 134.4, 130.9, 130.0, 129.8, 129.2, 128.9, 128.6, 128.6, 128.5, 128.4 (2C), 128.3, 128.2, 126.1, 126.0, 125.9, 39.3, 37.9, 34.7, 21.2; LRMS (EI, 70 eV) m/z (%): 208 (M+, 91), 193 (92), 178 (38), 115 (100); HRMS m/z (ESI) calcd for C16H17 ([M+H]+) 209.1325, found 209.1332.

Supporting Information Available: Copies of 1H and 13C spectra. This material is available free of charge via the Internet at http://pubs.acs.org.

Acknowledgments. We thank the Natural Science Foundation of China (Nos. 21472039 and 21625203) and the Jiangxi Province Science and Technology Project (Nos. 20165BCB18007 and 20171ACB20015) for financial support.

References and notes (1) For selected reviews on the synthesis of cyclopentene derivatives, see: (a) Hudlicky, T.; Price, J. D. Anionic Approaches to the Construction of Cyclopentanoids. Chem. Rev. 1989, 89, 14671486. (b) Berecibar, A.; Grandjean, C.; Siriwardena, A. Synthesis and Biological Activity of


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Natural Aminocyclopentitol Glycosidase Inhibitors: Mannostatins, Trehazolin, Allosamidins, and Their Analogues. Chem. Rev. 1999, 99, 779-844. (c) Das, S.; Chandrasekhar, S.; Yadav, J. S.; Grée, R. Recent Developments in the Synthesis of Prostaglandins and Analogues. Chem.

Rev. 2007, 107, 3286-3337. (d) Wu, H.; Zhang, H.; Zhao, G. An Enantioselective Total Synthesis of Pinnaic Acid. Tetrahedron 2007, 63, 6454-6461. (e) Heasley, B. Stereocontrolled Preparation of Fully Substituted Cyclopentanes: Relevance to Total Synthesis. Eur. J. Org.

Chem. 2009, 1477-1489. (f) Zeng, X.-P.; Cao, Z.-Y.; Wang, Y.-H.; Zhou, F.; Zhou, J. Catalytic Enantioselective Desymmetrization Reactions to All-Carbon Quaternary Stereocenters. Chem.

Rev. 2016, 116, 7330-7396. For a recent review on the synthesis of indenes, see: (g) Gabriele, B.; Mancuso, R.; Veltri, L. Recent Advances in the Synthesis of Indanes and Indenes. Chem.

Eur. J. 2016, 22, 5056-5094. (2) Carbovir: (a) Vince, R.; Hua, M.; Brownel, J.; Dalugue, S.; Lee, F.; Shannon, W. M.; Lavelle, G. C.; Qualls, J.; Weislow, O. S.; Kiser, R.; Canonico, P. G.; Schultz, R. H.; Narayanan, V. L.; Mayo, J. G.; Shoemaker, R. H.; Boyd, M. R. Potent and Selective Activity of A New Carbocyclic Nucleoside Analog (Carbovir: NSC 614846) Against Human Immunodeficiency Virus In Vitro. Biochem. Biophys. Res. Commun. 1988, 156, 1046-1053. 4-ACPCA: (b) Kumar, R. J.; Chebib, M.; Hibbs, D. E.; Kim, H.-L.; Johnston, G. A. R.; Salam, N. K.; Hanrahan, J. R. Novel γ-Aminobutyric Acid ρ1 Receptor Antagonists; Synthesis, Pharmacological Activity and

Structure-Activity Relationships. J. Med. Chem. 2008, 51, 3825-3840, and references cited

therein. Gukulenin: (c) Park, S. Y.; Choi, H.; Hwang, H.; Kang, H.; Rho, J.-R. Gukulenins A and B, Cytotoxic Tetraterpenoids from the Marine Sponge Phorbas gukulensis. J. Nat. Prod. 2010, 73, 734-737. A chemokine receptor modulator: (d) Robert, M. W.; Rhona, J. C.


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