annulation of Î³-butyrolactone fused donor-acceptor cyclopropanes

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SnCl4-Promoted [3+2] annulation of #-butyrolactone fused donor-acceptor cyclopropanes with nitriles: Access to #-butyrolactone fused 1-pyrrolines V. John Tamilarasan, and Srinivasan Kannupal J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01155 • Publication Date (Web): 07 Jun 2019 Downloaded from http://pubs.acs.org on June 7, 2019

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The Journal of Organic Chemistry

SnCl4-Promoted [3+2] annulation of γ-butyrolactone fused donor-acceptor cyclopropanes with nitriles: Access to γ-butyrolactone fused 1-pyrrolines V. John Tamilarasan and Kannupal Srinivasan* School of Chemistry, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India [email protected]

H Ar

Ar2

1

EtO2C

O O

+

R

N

SnCl4 (1 equiv.) 1,2-DCE 40 C

Ar2 H Ar

O

O CO2Et

1

R N 15-75% 18 examples

Abstract: The [3+2] annulation of γ-butyrolactone fused donor-acceptor cyclopropanes with nitriles has been explored for the access of γ-butyrolactone fused 1-pyrrolines. The annulation was promoted by tin(IV) chloride and the products were obtained as single diastereomers in moderate to good yields. The products were synthetically important and a couple of them were subjected to tandem reductive ring opening/cyclization to give respective γ-butyrolactone fused γ-butyrolactams in good yields.

The [3+2] annulation reactions of donor-acceptor (D-A) cyclopropanes are versatile tools for the construction of five-membered cyclic compounds such as cyclopentanes,1 cyclopentenes,2 tetrahydrofurans,3 pyrrolidines,4 1-pyrrolines,5 pyrroles,6 isoxazolidines7 and pyrazolidines.8 The high reactivity of D-A cyclopropanes in the reactions is attributed to the presence of inherent

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strain in the cyclopropane ring plus the additional strain bestowed by the push-pull effect of the donor-acceptor substituents. The strain and hence the reactivity of such D-A cyclopropanes could be further enhanced or altered by the fusion of another ring to the D-A cyclopropanes.9 This fact coupled with our experience with aroyl group substituted D-A cyclopropanes10 motivated us to prepare γ-butyrolactone fused D-A cyclopropanes such as 1 for exploring their synthetic potential (Scheme 1). Recently, Yang and coworkers have reported [3+2] annulations of these cyclopropanes with isothiocyanates, carbodiimides and aldehydes/ketones to obtain γbutyrolactone fused dihydrothiophen-2-imines, pyrrolidin-2-imines and tetrahydrofurans, respectively (Scheme 1, eq 1).11,12 We have previously reported [3+2] annulation of aroyl group substituted D-A cyclopropanes with nitriles for the access of 1-pyrrolines (Scheme 1, eq 2).5b Herein we report an extension of the methodology to γ-butyrolactone fused D-A cyclopropanes for the highly diastereoselective synthesis of γ-butyrolactone fused 1-pyrrolines having four contiguous stereocenters (Scheme 1, eq 3).


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Ar2

H Ar1

O

EtO2C

+

R N C S or R N C N R R

O

1

or

Ar

Ar2

+

S

1,2-DCE

or

2

O

Ar

Ar1

N

R

O

SnCl4

Ar

1,2-DCE

2

O

Ar1

O

CO2Et CO2Et

1

O CO2Et

N R

N R

(1)

O CO2Et R R

(2)

R

N

O

H Ar

N R

H

CO2Et

Ar1

1

O

R

Ar2

O CO2Et or

H

FeCl3 or Sn(OTf)2

Our previous work: EtO2C

O

Ar2

Yang et al.:

This work: H Ar1

Ar2 O

EtO2C

O

+

R

N

SnCl4 1,2-DCE

Ar2

O

H Ar1

O CO2Et

N

(3)

R

1

Scheme 1. [3+2] annulations of γ-butyrolactone fused/aroyl substituted D-A cyclopropanes

The γ-butyrolactone fused D-A cyclopropanes 1 required for the present study were prepared as single diastereomers by a simple reduction of respective aroyl group substituted D-A cyclopropanes using NaBH4 and subsequent spontaneous lactonization (Table 1).13



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Table 1. Preparation of γ-butyrolactone fused D-A cyclopropanes EtO2C

CO2Et Ar2

Ar1 O

NaBH4 MeOH, 0 C 71-88 %

Ar2

H Ar1 EtO2C

O 1

O

Entry Ar1 Ar2 Yield of 1 (%)a,b 1 Ph Ph 79 (1a) 2 4-MeC6H4 Ph 88 (1b) 3 4-MeOC6H4 Ph 83 (1c) 4 4-ClC6H4 Ph 85 (1d) 5 4-O2NC6H4 Ph 76 (1e) 6 Ph 4-MeC6H4 87 (1f)c 7 Ph 4-MeOC6H4 81 (1g) 8 Ph 4-ClC6H4 84 (1h) 9 Ph 4-O2NC6H4 71 (1i) a b Isolated yield. all products are formed as single diastereomers. cthe structure was confirmed by X-ray analysis.14

We began our study by choosing γ-butyrolactone fused cyclopropane 1a (Ar1 = Ar2 = Ph) and benzonitrile (2a) as model substrates for optimizing the reaction conditions for the [3+2] annulation (See the supporting information for complete details). In our previous study (Scheme 1, eq 2),5b we had identified 1 equiv of SnCl4 in 1,2-dichloroethane at room temperature as optimal conditions for the [3+2] annulation of aroyl group substituted D-A cyclopropanes with nitriles. After screening various parameters in the present study, we found that the [3+2] annulation between 1a and 2a proceeds better with the same Lewis acid and solvent [SnCl4 (1 equiv) and 1,2-dichloroethane], but at a slightly elevated temperature (40 °C). Next, we investigated the scope of the transformation with respect to various γbutyrolactone fused D-A cyclopropanes 1 and nitriles 2 and the results are summarized in Table


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2. First, we reacted cyclopropane 1a with various aromatic and aliphatic nitriles (entries 1-8). The electronic nature and position of substituents on the aromatic nitriles influenced the yield of the product pyrrolines 3a-h significantly. The yields were higher for aromatic nitriles having electron donating substituents in the p-position as compared to those with halogen substituents in the position (the inductive effect of the halogens may be the culprit) (entries 2-5). In case of pnitrobenzonitrile, only a trace amount of 3f is formed due to strong electron withdrawing nature of the nitro group (entry 6). The placement of a halogen substituent in the o-position of aromatic nitrile is also found to decrease the yield considerably, probably owing to steric reasons (entry 7). The reaction also proceeded smoothly with an aliphatic nitrile and the corresponding product 3h was produced in 75% yield (entry 8). Next, we reacted cyclopropanes having different Ar1 rings with benzonitrile (2a) (entries 9-12). Again the yields were better for cyclopropanes having p-tolyl or p-anisyl as Ar1 as compared with a cyclopropane in which Ar1 was p-chlorophenyl (entries 9-11). The yield was poor for a cyclopropane in which Ar1 was p-nitrophenyl due to the reduced electrophilicity of the cyclopropane carbon to which this group is attached (entry 12).5b,15 We also examined the scope of the reaction for cyclopropanes having different Ar2 rings using benzonitrile (2a) (entries 13-16). The presence of electron donating (except methoxy group) and halogen substituents in the p-position of Ar2 does not affect the yield of the products (entries 13-15) while electron withdrawing nitro group in the position lowers the yield to some extent (entry 16). We also tested cyclopropanes having different Ar1 and Ar2 rings and different nitriles in the annuation and observed the formation of the respective products in moderate yields (entries 17-19). All the products are formed as single diastereomers, which are the only isolable products from the reaction mixtures. The stereochemistry assigned to the products was unequivocally supported by X-ray analysis of one of the products, 3m.16



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Table 2. Scope of [3+2] annulation of γ-butyrolactone fused D-A cyclopropanes with nitrilesa H Ar1

O

EtO2C 1

a

Ar2

+

R

N 2

O

SnCl4 (1 equiv.) 1,2-DCE 40 C

Ar2

O

H Ar

1

O CO2Et

N 3

R

Entry

Ar1

Ar2

R

Yield (%)a

1

Ph

Ph

Ph

3a, 73 (4 h)

2

Ph

Ph

4-MeC6H4

3b, 65 (4 h)

3

Ph

Ph

4-MeOC6H4

3c, 68 (4 h)

4

Ph

Ph

4-ClC6H4

3d, 55 (4 h)

5

Ph

Ph

4-BrC6H4

3e, 58 (4 h)

6

Ph

Ph

4-O2NC6H4

3f, trace (15 h)

7

Ph

Ph

2-ClC6H4

3g, 42 (6 h)

8

Ph

Ph

n-Bu

3h, 75 (5 h)b

9

4-MeC6H4

Ph

Ph

3i, 65 (4 h)

10

4-MeOC6H4

Ph

Ph

3j, 62 (4 h)

11

4-ClC6H4

Ph

Ph

3k, 52 (4 h)

12

4-O2NC6H4

Ph

Ph

3l, 15 (24 h)b

13

Ph

4-MeC6H4

Ph

3m, 71 (4 h)

14

Ph

4-MeOC6H4

Ph

3n, 57 (4 h)

15

Ph

4-ClC6H4

Ph

3o, 68 (4 h)

16

Ph

4-O2NC6H4

Ph

3p, 55 (6 h)

17

4-MeC6H4

Ph

4-MeC6H4

3q, 59 (4 h)

18

Ph

4-MeC6H4

4-ClC6H4

3r, 54 (5 h)

19

Ph

4-ClC6H4

4-MeC6H4

3s, 50 (5 h)

b

Isolated yield. conducted under nitrogen atmosphere.


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Based on the literature reports3c,11,12 and our previous work,5b we propose a plausible mechanism outlined in Scheme 2 for the formation of products 3 from D-A cyclopropanes 1 and nitriles 2. The Lewis acid (SnCl4) coordinates to the ester and lactone carbonyls of cyclopropane 1 and the coordination weakens the C1-C2 bond. The nucleophilic attack of nitrile 2 on C2 of cyclopropane 1 breaks the C1-C2 bond, which results in a dipolar intermediate. The substituents attached to C2 undergo a 120° rotation to bring the nitrilium carbon close to the carbanion of the intermediate. This facilitates the attack of the carbanion on the nitrilium carbon yielding the products 3 in a diatereoselective manner. EtO H Ar1 R

N 2

Ar2

O

Ar1

3 1

H

1

N 3

R

O

O R

Ar1

SnCl4

O

2

CO2Et

H

O Ar2

H 1

Ar

N

N

R

O

H

H Ar1

O

120 2

H CO2Et Ar2 O

H CO2Et Ar2

O

H CO2Et Ar2 O

N

O R

Scheme 2. Mechanism for the [3+2] annulation (the Lewis acid coordination is not shown in the intermediate structures for clarity) The product pyrrolines 3 could serve as potential synthetic precursors to other important compounds, and to prove this point, we subjected a couple of the products to reduction using sodium cyanoborohydride with a view to obtain the respective pyrrolidines.5b Surprisingly, upon reduction with excess sodium cyanoborohydride, they underwent reductive ring opening via



Page 8 of 24

pyrrolidine intermediates followed by cyclization to give γ-butyrolactone fused γ-butyrolactams 4 (Scheme 3). This intriguing observation clearly indicates the advantage of having γbutyrolactone ring fusion in the structure of the product pyrrolines 3. It may be noted that lactone fused γ-butyrolactam core is present in biologically important natural products such as neooxazolomycin and salinosporamide A.17

O

Ar H

CO2Et

Ph

NaCNBH3 (4 equiv)

Ar

MeOH/AcOH rt, 30 min

Ph

O Ph

N

O

O

H Ph

H

O

Ar Ph

N H 4 Ar = Ph; 4a; 62% Ar = 4-MeC6H4; 4b; 67%

H Ph

O CO2Et

N H

Ph

O

O Ph

H

3

Ar

O

H

CO2Et NH2

Scheme 3. Synthetic utility of products 3.

In conclusion, we have developed a convenient methodology for the access of γbutyrolactone fused 1-pyrrolines through SnCl4-promoted [3+2] annulation of γ-butyrolactone fused donor-acceptor cyclopropanes with nitriles. The methodology has a reasonably wide substrate scope and provides the products as single diastereomers in moderate to good yields. The products are found to be potential precursors for the synthesis of γ-butyrolactone fused γbutyrolactams.


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EXPERIMENTAL SECTION General remarks. Melting points were determined by the open capillary tube method and are uncorrected. The 1H and

13

C NMR spectra were recorded on a 400 MHz NMR spectrometer.

High resolution mass spectra (ESI) were recorded on a Q-TOF mass spectrometer. Low resolution mass spectra (ESI) were recorded on a LC−MS spectrometer. Elemental analyses were performed on a CHN analyzer. X-ray crystallographic data were collected on a CCD diffractometer using graphite-monochromated Mo-Kα radiation. Thin layer chromatography (TLC) was performed on pre-coated alumina sheets and detected under UV light. Silica gel (100200 mesh) was used for column chromatography. General procedure for the synthesis of γ-butyrolactone fused D-A cyclopropanes: To a solution of cyclopropane (5.0 mmol) in MeOH (10 mL) at 0 oC, NaBH4 (185 mg, 5.0 mmol) was added in one portion and the reaction mixture was stirred at 0 oC for 30-45 min. After completion of the reaction, the solvent was removed under reduced pressure. The reaction mixture was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine solution and dried over anhydrous Na2SO4. The removal of solvent under reduced pressure gave the crude product, which was purified by column chromatography using EtOAc/hexane (1:9) to afford γ-butyrolactone fused D-A cyclopropanes. Ethyl 2-oxo-4,6-diphenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1a):11 White solid. Yield: 1.273 g (79%). Mp: 104–108 oC. 1H NMR (400 MHz, CDCl3): δ 7.45–7.40 (m, 5H), 7.32–7.25 (m, 5H), 5.45 (s, 1H), 4.01–3.94 (m, 2H), 3.34 (d, J = 5.6 Hz, 1H), 3.06 (d, J = 5.2 Hz, 1H), 0.91 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 169.6, 163.3, 138.4, 131.8, 129.4,

129.2, 128.7, 128.5, 128.2, 126.0, 79.8, 61.8, 38.5, 37.6, 33.7, 13.7 ppm.



Page 10 of 24

Ethyl 2-oxo-4-phenyl-6-(p-tolyl)-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1b):11 White solid. Yield: 1.480 g (88%). Mp: 110–114 oC. 1H NMR (400 MHz, CDCl3): δ 7.44-7.40 (m, 5H), 7.16–7.10 (m, 4H), 5.44 (s, 1H), 4.02–3.96 (m, 2H), 3.31 (d, J = 5.6 Hz, 1H), 3.03 (d, J = 5.2 Hz, 1H), 2.32 (s, 3H), 0.95 (t, J = 7.0 Hz, 3H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ

169.8, 163.5, 138.4, 138.1, 129.4, 129.2, 128.6, 126.0, 79.8, 61.8, 38.5, 37.7, 33.8, 21.2, 13.8 ppm. Ethyl

6-(4-methoxyphenyl)-2-oxo-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate

(1c):11 White solid. Yield: 1.462 g (83%). Mp: 106–110 oC. 1H NMR (400 MHz, CDCl3): δ 7.44–7.40 (m, 5H), 7.19 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 5.43 (s, 1H), 4.03–3.97 (m, 2H), 3.79 (s, 3H), 3.39 (d, J = 5.2 Hz, 1H), 3.03 (d, J = 5.6 Hz, 1H), 0.97 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 169.7, 163.5, 159.5, 138.4, 130.0, 129.3, 129.2,

126.0, 123.6, 113.9, 79.7, 61.8, 55.3, 38.5, 37.6, 33.9, 13.9 ppm. Ethyl 6-(4-chlorophenyl)-2-oxo-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1d):11 White solid. Yield: 1.516 g (85%). Mp: 108–112 oC. 1H NMR (400 MHz, CDCl3): δ 7.45–7.38 (m, 5H), 7.29 (d, J = 8.4 Hz, 2H), 7.21–7.19 (m, 2H), 5.45 (s, 1H), 4.01 (q, J = 7.2 Hz, 2H), 3.29 (d, J = 5.6 Hz, 1H), 3.02 (d, J = 5.6 Hz, 1H), 0.97 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H} NMR

(100 MHz, CDCl3): δ 169.4, 163.3, 138.2, 134.3, 130.4, 130.11, 130.05, 129.5, 129.2, 128.8, 128.7, 126.0, 125.9, 79.7, 62.0, 38.4, 36.9, 33.9, 13.8 ppm. Ethyl

6-(4-nitrophenyl)-2-oxo-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate

(1e):11

White solid. Yield: 1.396 g (76%). Mp: 102-106 oC. 1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 8.4 Hz, 2H), 7.47–7.40 (m, 7H), 5.50 (s, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.37 (d, J = 5.6 Hz, 1H), 3.10 (d, J = 5.2 Hz, 1H), 1.02 (t, J = 7.2 Hz, 3H) ppm.

13


168.9, 163.1, 147.7, 139.3, 137.8, 129.71, 129.66, 129.3, 125.9, 123.6, 79.8, 62.4, 38.6, 36.3,


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34.4, 13.9 ppm. Ethyl 2-oxo-6-phenyl-4-(p-tolyl)-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1f):11 White solid. Yield: 1.463 g (87%). Mp: 86–90 oC. 1H NMR (400 MHz, CDCl3): δ 7.45–7.40 (m, 5H), 7.16–7.11 (m, 4H), 5.44 (s, 1H), 4.03–3.97 (m, 2H), 3.31 (d, J = 5.6 Hz, 1H), 3.04 (d, J = 5.6 Hz, 1H), 2.32 (s, 3H), 0.95 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 169.7, 163.4, 138.4, 129.3, 129.2, 128.7, 128.6, 126.0, 79.8, 61.8, 38.5, 37.7, 33.8, 21.1, 13.8 ppm. Ethyl 4-(4-anisyl)-2-oxo-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1g):11 White solid. Yield: 1.427 g (81 %). Mp: 78–82 oC. 1H NMR (400 MHz, CDCl3): δ 7.36–7.26 (m, 7H), 6.96 (d, J = 8.4 Hz, 2H), 5.40 (s, 1H), 4.03–3.95 (m, 2H), 3.84 (s, 3H), 3.32 (d, J = 5.2 Hz, 1H), 3.03 (d, J = 5.6 Hz, 1H), 0.91 (t, J = 7.2 Hz, 3H) ppm.

13


169.7, 163.5, 160.4, 131.9,130.4, 128.7, 128.5, 128.2, 127.7, 114.5, 79.9, 61.8,55.4, 38.8, 37.6, 33.5, 13.8 ppm. Ethyl 4-(4-chlorophenyl)-2-oxo-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1h): White solid. Yield: 1.499 g (84 %). Mp: 72–76 oC. 1H NMR (400 MHz, CDCl3): δ 7.42-7.40 (m, 2H), 7.36-7.34 (m, 2H), 7.32-7.30 (m, 3H), 7.26-7.24 (m, 2H), 5.43 (s, 1H), 4.00–3.92 (m, 2H), 3.29 (d, J = 5.6 Hz, 1H), 3.05 (d, J = 5.2 Hz, 1H), 0.89 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 169.5, 163.2, 136.9, 135.3, 131.6,129.4, 128.9, 128.7, 128.6, 128.5, 128.4, 127.4, 127.2, 79.0, 61.9, 38.4, 37.6, 33.6, 13.7 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H18ClO4 357.0888; Found 357.0895. Ethyl 4-(4-nitrophenyl)-2-oxo-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1i):11 White solid. Yield: 1.304 g (71 %). Mp: 106–110 oC. 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.34–7.32 (m, 3H), 7.28–7.26 (m, 2H), 5.57 (s, 1H), 4.00-3.95 (m, 2H), 3.31 (d, J = 5.2 Hz, 1H), 3.12 (d, J = 5.2 Hz, 1H), 0.91 (t, J = 7.0 Hz, 3H)



ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 169.0, 162.9, 148.5, 145.2, 131.3, 128.6, 128.5,

126.8, 124.5, 78.2, 62.1, 38.1, 37.6, 33.5, 13.7 ppm. General procedure for the synthesis of γ-butyrolactone fused 1-pyrrolines 3: To a solution of γ-butyrolactone fused cyclopropane 1(1.0 mmol), nitrile 2 (1.2 mmol) in dry 1,2dichloroethane (3 mL) was added SnCl4 (1.0 mmol, 0.261 g) and the reaction mixture was stirred at 40 oC on oil bath for 4-24 h. After completion of the reaction, the reaction mixture was quenched with water and extracted with dichloromethane. The organic layer was washed with brine (2 × 10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography using EtOAc/hexane (1:9) to afford γ-butyrolactone fused 1-pyrrolines 3. Ethyl 3-oxo-1,4,6-triphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-carboxylate (3a): White solid. Yield: 311 mg (73%). Mp: 138–142 oC. 1H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 7.2 Hz, 2H), 7.51–7.45 (m, 3H), 7.35–7.34 (m, 3H), 7.28–7.25 (m, 2H), 7.21 (d, J = 7.2 Hz, 1H), 7.18–7.14 (m, 2H), 6.62 (d, J = 7.6 Hz, 2H), 5.73 (d, J = 6.4 Hz, 1H), 4.86 (d, J = 6.8 Hz, 1H), 4.37–4.29 (m, 2H), 3.91 (t, J = 7.0 Hz, 1H), 1.27 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 169.0, 167.1, 165.4, 138.1, 137.4, 131.6, 131.3, 129.7, 128.9, 128.8, 128.49, 128.46, 128.1, 127.7, 126.3, 80.4, 75.4, 73.9, 63.1, 60.4, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H24NO4 426.1700; Found 426.1705. Ethyl

3-oxo-1,6-diphenyl-4-(p-tolyl)-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-

carboxylate (3b): White solid. Yield: 286 mg (65%). Mp: 140–144 oC. 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8 Hz, 2H), 7.35–7.33 (m, 3H), 7.28–7.23 (m, 4H), 7.20 (d, J = 6.8 Hz, 1H), 7.17–7.13 (m, 2H), 6.61 (d, J = 7.2 Hz, 2H), 5.71 (d, J = 6.8 Hz, 1H), 4.85 (d, J = 6.8 Hz, 1H), 4.38–4.26 (m, 2H), 3.89 (t, J = 6.8 Hz, 1H), 2.40 (s, 3H), 1.27 (t, J = 7.0 Hz, 3H) ppm. 13C{1H}


Page 12 of 24

Page 13 of 24 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


NMR (100 MHz, CDCl3): δ 169.1, 167.2, 165.3, 142.1, 138.2, 137.5, 129.7, 129.2, 128.8, 128.7, 128.6, 128.5, 128.0, 127.7, 126.3, 80.4, 75.3, 73.9, 63.0, 60.4, 21.6, 14.0 ppm; HRMS (ESITOF) m/z: [M+H]+ Calcd for C28H26NO4 440.1856; Found 440.1865. Ethyl 4-(4-methoxyphenyl)-3-oxo-1,6-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)carboxylate (3c): White solid. Yield: 310 mg (68%); Mp: 132–136 oC. 1H NMR (400 MHz, CDCl3): δ 8.27 (d, J = 8.8 Hz, 2H), 7.35–7.33 (m, 3H), 7.28–7.25 (m, 2H), 7.20 (d, J = 7.2 Hz, 1H), 7.17–7.14 (m, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 7.2 Hz, 2H), 5.69 (d, J = 6.8 Hz, 1H), 4.85 (d, J = 7.2 Hz, 1H), 4.38–4.26 (m, 2H), 3.91–3.86 (m, 4H), 1.28 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 169.3, 167.2, 164.6, 162.3, 138.2, 137.7, 131.5, 128.8, 128.7, 128.5, 128.0, 127.7, 126.3, 124.0, 113.8, 80.4, 75.2, 73.8, 63.0, 60.5, 55.5, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C28H26NO5 456.1805; Found 456.1807. Ethyl

4-(4-chlorophenyl)-3-oxo-1,6-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-

carboxylate (3d): White solid. Yield: 253 mg (55%). Mp: 138–142 oC. 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.8 Hz, 2H), 7.36-7.35 (m, 3H), 7.26–7.23 (m, 3H), 7.19–7.15 (m, 2H), 6.62 (d, J = 7.6 Hz, 2H), 5.79 (d, J = 6.8 Hz, 1H), 4.86 (d, J = 7.2 Hz, 1H), 4.37–4.29 (m, 2H), 3.92 (t, J = 7.0 Hz, 1H), 1.28 (t, J = 7.0 Hz, 3H) ppm.

13

C{1H} NMR

(100 MHz, CDCl3): δ 169.0, 166.9, 164.5, 137.9, 137.1, 131.7, 131.2, 130.2, 128.88, 128.82, 128.5, 128.2, 127.7, 126.5, 126.3, 80.6, 75.4, 73.9, 63.2, 60.2, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23ClNO4 460.1310; Found 460.1316. Ethyl

4-(4-bromophenyl)-3-oxo-1,6-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-

carboxylate (3e): White solid. Yield: 293 mg (58%). 110-118 oC. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.4 Hz, 2H), 7.44 (d, 8.4 Hz, 2H), 7.36–7.35(m, 3H), 7.26–7.21 (m, 3H), 7.18–7.15 (m, 2H), 6.62 (d, J = 7.2 Hz, 2H), 5.71 (d, J = 6.8 Hz, 1H), 4.86 (d, J = 7.2 Hz, 1H), 4.37–4.29



(m, 2H), 3.92 (t, J = 7.0 Hz, 1H), 1.28 (t, J = 7.2 Hz, 3H) ppm.

Page 14 of 24

13

C{1H} NMR (100 MHz,

CDCl3): δ 169.0, 166.9, 164.4, 137.94, 137.91, 137.2, 131.1, 129.8, 129.2, 128.89, 128.83, 128.7, 128.5, 128.2, 127.7, 126.3, 80.6, 75.4, 73.9, 63.2, 60.3, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23BrNO4 504.0805; Found 504.0816. Ethyl


carboxylate (3g): White solid. Yield: 193 mg (42%). Mp: 156-160 oC. 1H NMR (400 MHz, CDCl3): δ 7.66 (dd, J = 7.2, 1.6 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.43–7.35 (m, 5H), 7.31–7.30 (m, 2H), 7.24–7.21 (m, 1H), 7.17–7.13 (m, 2H), 6.56 (d, J = 7.6 Hz, 2H), 5.77 (d, J = 6.4 Hz, 1H), 5.06 (d, J = 8 Hz, 1H), 4.40-4.32 (m, 2H), 3.92 (t, J = 7.0 Hz, 1H), 1.35 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 168.1, 166.0, 165.5, 137.9, 136.8, 133.0, 131.9, 131.0, 130.3, 130.0, 128.9, 128.8, 128.5, 128.1, 127.7, 126.7, 126.5, 80.8, 76.5, 63.3, 59.5, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23ClNO4 460.1310; Found 460.1318. Ethyl

4-butyl-3-oxo-1,6-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-carboxylate

(3h): Pale yellow paste. Yield: 304 mg (75 %). 1H NMR (400 MHz, CDCl3): δ 7.31 (s, 3H), 7.21–7.12 (m, 5H), 6.58 (d, J = 7.6 Hz, 2H), 5.53–5.52 (m, 1H), 4.77 (d, J = 6.8 Hz, 1H), 4.33– 4.28 (m, 2H), 3.77 (t, J = 6.8 Hz, 1H), 2.75–2.71 (m, 2H), 1.87–1.80 (m, 2H), 1.52–1.42 (m, 2H), 1.32 (t, J = 7.2 Hz, 3H), 0.98 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 170.4, 169.1, 166.1, 138.4, 137.5, 128.8, 128.7, 128.5, 128.0, 127.5, 126.24, 126.20, 81.0, 76.1, 75.4, 63.0, 57.8, 30.3, 28.6, 22.6, 14.03, 13.99 ppm. MS (ESI) m/z: 406 [M+H]+. Anal Calcd for C25H27NO4: C 74.05, H 6.71, N 3.45; Found: C 74.29, H 6.84, N 3.39. Ethyl


carboxylate (3i): White solid. Yield: 286 mg (65%). Mp: 170-174 oC. 1H NMR (400 MHz,


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CDCl3): δ 8.29–8.27 (m, 2H), 7.52 (m, 3H), 7.25–7.15 (m, 7H), 6.67 (d, J = 7.2 Hz, 2H), 5.71 (d, J = 6.8 Hz, 1H), 4.87 (d, J = 6.8 Hz, 1H), 4.37–4.25 (m, 2H), 3.87 (t, J = 7.0 Hz, 1H), 2.39 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 169.1, 167.2, 165.2,

138.3, 137.8, 134.3, 131.5, 131.3, 129.7, 129.5, 128.7, 128.4, 127.6, 126.3, 80.4, 75.4, 73.8, 63.0, 60.4, 21.2, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H] + Calcd for C28H26NO4 440.1856; Found 440.1855. Ethyl 6-(4-methoxyphenyl)-3-oxo-1,4-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)carboxylate (3j): White solid. Yield: 282 mg (62%). Mp: 130–134 oC. 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 6.8 Hz, 2H), 7.50–7.44 (m, 3H), 7.25–7.16 (m, 5H), 6.88 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 6.8 Hz, 2H), 5.69 (d, J = 6.8 Hz, 1H), 4.88 (d, J = 6.8 Hz, 1H), 4.37–4.24 (m, 2H), 3.87 (t, J = 7.0 Hz, 1H), 3.83 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H} NMR (100

MHz, CDCl3): δ 169.1, 167.2, 165.1, 159.5, 138.3, 131.6, 131.3, 129.7, 129.5, 128.78, 128.73, 128.5, 128.4, 126.3, 114.2, 80.4, 75.1, 73.8, 63.0, 60.5, 55.5, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C28H26NO5 456.1805; Found 456.1809. Ethyl


carboxylate (3k): White solid. Yield: 239 mg (52%). Mp: 168–172 oC. 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 7.2 Hz, 2H), 7.54–7.46 (m, 3H), 7.33–7.31 (m, 2H), 7.25–7.20 (m, 5H), 6.70 (d. J = 7.2 Hz, 2H), 5.67 (d, J = 6.4 Hz, 1H), 4.78 (d, J = 7.2 Hz, 1H), 4.38–4.29 (m, 2H), 3.93 (t, J = 7.0 Hz, 1H), 1.28 (t, J = 7.0 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 168.7, 166.9, 165.7, 137.6, 135.9, 133.9, 131.8, 131.1, 129.7, 129.0, 128.9, 128.6, 128.5, 126.5, 80.4, 74.5, 73.9, 63.2, 60.2, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23ClNO4 460.1310; Found 460.1317.



Ethyl

Page 16 of 24

6-(4-nitrophenyl)-3-oxo-1,4-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-

carboxylate (3l): White solid. Yield: 71 mg (15%). Mp: 136–140 oC. 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 7.6 Hz, 2H), 7.53–7.45 (m, 3H), 7.36–7.35 (m, 3H), 7.28–7.25 (m, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.50 (d. J = 8.4 Hz, 2H), 5.71 (d, J = 6.4 Hz, 1H), 4.82 (d, J = 7.2 Hz, 1H), 4.37–4.28 (m, 2H), 3.86–3.82 (m, 1H), 1.27 (t, J = 7.0 Hz, 3H) ppm.

13

C{1H} NMR (100

MHz, CDCl3): δ 168.8, 166.9, 165.3, 137.3, 136.6, 134.7, 131.7, 131.2, 129.7, 128.9, 128.7, 128.6, 128.5, 128.2, 127.8, 127.7, 79.6, 75.1, 73.9, 63.2, 60.5, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H] + Calcd for C27H23N2O6 471.1551; Found 471.1549. Ethyl


carboxylate (3m): White solid. Yield: 312 mg (71%). Mp: 146–150 oC. 1H NMR (400 MHz, CDCl3): δ 8.30–8.28 (m, 2H), 7.51–7.43 (m, 3H), 7.34–7.33 (m, 3H), 7.27–7.25 (m, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.50 (d, J = 8.0 Hz, 2H), 5.71 (d, J = 6.8 Hz, 1H), 4.83 (d, J = 7.2 Hz, 1H), 4.38–4.26 (m, 2H), 3.89 (t, J = 6.8 Hz, 1H), 2.26 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 169.1,167.2, 165.4, 138.6, 137.4, 135.1, 131.3, 129.7, 129.2, 128.8, 128.5, 128.0, 127.7, 126.3, 80.5, 75.4, 74.0, 63.1, 60.4, 21.2, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C28H26NO4 440.1856; Found 440.1859. Ethyl 1-(4-methoxyphenyl)-3-oxo-4,6-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)carboxylate (3n): White paste. Yield: 260 mg (57%). 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 7.6 Hz, 2H), 7.51–7.45 (m, 3H), 7.24–7.17 (m, 5H), 6.89 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 7.6 Hz, 2H), 5.70 (d, J = 6.8 Hz, 1H), 4.88 (d, J = 6.8 Hz, 1H), 4.35–4.29 (m, 2H), 3.89–3.85 (m, 4H), 1.26 (t, J = 6.8 Hz, 3H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 169.0, 167.1, 165.4,

159.8, 137.4, 131.6, 131.3, 129.9, 129.7, 128.8, 128.5, 128.4, 128.0, 127.9, 127.7, 126.3, 113.8,


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80.5, 75.1, 74.1, 63.1, 60.4, 55.3, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C28H26NO5 456.1805; Found: 456.1807. Ethyl

1-(4-chlorophenyl)-3-oxo-6-phenyl-4-(p-tolyl)-6,6a-dihydro-1H-furo[3,4-c]pyrrole-

3a(3H)-carboxylate(3o): White solid. Yield: 313 mg (68%). Mp: 142–146 oC. 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 7.2 Hz, 2H), 7.54–7.46 (m, 3H), 7.37–7.36 (m, 3H), 7.28–7.27 (m, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 8.4 Hz, 2H), 5.71 (d, J = 6.4 Hz, 1H), 4.83 (d, J = 7.6 Hz, 1H), 4.41–4.28 (m, 2H), 3.83 (t, J = 7.0 Hz, 1H), 1.28 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H}

NMR (100 MHz, CDCl3): δ 168.8, 166.9, 165.3, 137.3, 136.6, 134.7, 132.2, 131.7, 131.2, 129.7, 129.2, 128.9, 128.7, 128.5, 128.2, 127.8, 127.7, 79.6, 75.1, 73.9, 63.2, 60.5, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23ClNO4 460.1310; Found 460.1313. Ethyl

1-(4-nitrophenyl)-3-oxo-4,6-diphenyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-

carboxylate (3p): White solid. Yield: 259 mg (55%). Mp: 132–136 oC. 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 7.6 Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H), 7.55 (m, 3H), 7.42–7.38 (m, 3H), 7.31–7.29 (m, 2H), 6.70 (d, J = 8.8 Hz, 2H), 5.73 (d, J = 6.4 Hz, 1H), 4.96 (d, J = 7.2 Hz, 1H), 4.41–4.28 (m, 2H), 3.82 (t, J = 7.0 Hz, 1H), 1.28 (t, J = 7.0 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 168.5, 166.6, 165.3, 148.0, 145.1, 137.2, 131.8, 131.0, 129.7, 129.2, 128.5, 127.7, 127.2, 123.7, 78.8, 75.0, 73.7, 63.4, 60.6, 14.0 ppm; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23N2O6 471.1551; Found 471.1551. Ethyl 3-oxo-1-phenyl-4,6-di-p-tolyl-6,6a-dihydro-1H-furo[3,4-c]pyrrole-3a(3H)-carboxylate (3q): White solid. Yield: 295 mg (65%). Mp: 134–138 oC. 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.0 Hz, 2H), 7.28–7.26 (m, 2H), 7.22–7.15 (m, 7H), 6.66 (d, J = 7.2 Hz, 2H), 5.69 (d, J = 6.8 Hz. 1H), 4.87 (d, J = 7.2 Hz, 1H), 4.37–4.25 (m, 2H), 3.85 (t, J = 6.8 Hz, 1H), 2.41 (s, 3H), 2.39 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 169.2, 167.3,



165.1, 142.0, 138.4, 137.8, 134.5, 129.6, 129.4, 129.2, 128.62, 128.59, 128.4, 127.6, 126.3, 80.3, 75.3, 73.7, 63.0, 60.5, 21.6, 21.2, 14.0 ppm; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C29H28NO4 454.2013; Found 454.2013. Ethyl


3a(3H)-carboxylate (3r): White solid. Yield: 256 mg (54%). Mp: 138–142 oC. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.35 (t, J = 3.2 Hz, 3H), 7.25 (s, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 8.0 Hz, 2H), 5.70 (d, J = 6.8 Hz. 1H), 4.83 (d, J = 6.8 Hz, 1H), 4.38–4.29 (m, 2H), 3.90 (t, J = 7.0 Hz, 1H), 2.28 (s, 3H), 1.29 (t, J = 7.0 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 169.0, 167.0, 164.4, 138.7, 137.9, 137.2, 135.0, 131.1, 129.8, 129.5, 129.2, 128.9, 128.7, 128.1, 127.7, 127.5, 126.3, 80.6, 75.4, 74.1, 63.2, 60.2, 21.2, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C28H25ClNO4 474.1467; Found 474.1472. Ethyl


3a(3H)-carboxylate (3s): White solid. Yield: 237 mg (50%). 136–140 oC. 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.4 Hz, 2H), 7.36–7.34 (m, 3H), 7.27 (d, J = 7.6 Hz, 4H), 7.12 (d, J = 8.4 Hz, 2H), 6.50 (d, J = 8.4 Hz, 2H), 5.69 (d, J = 6.4 Hz. 1H), 4.82 (d, J = 7.2 Hz, 1H), 4.39–4.26 (m, 2H), 3.81 (t, J = 7.0 Hz, 1H), 2.41 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 168.9, 167.0, 165.2, 142.2, 137.5, 136.6, 134.6, 129.6, 129.2, 128.9, 128.7, 128.5, 128.2, 127.8, 127.7, 79.6, 75.0, 73.8, 63.1, 60.6, 21.6, 14.0 ppm. HRMS (ESI-TOF) m/z: [M+H] + Calcd for C28H25ClNO4 474.1467; Found: 474.1470. General procedure for the synthesis of γ-butyrolactone fused γ-butyrolactam 4: To a solution of γ-butyrolactone fused 1-pyrroline 3 (0.3 mmol) in MeOH/AcOH (3:1, 4 mL) was added NaCNBH3 (1.2 mmol, 75 mg) in one portion and reaction mixture was stirred at room temperature. After completion the reaction (30 min), the reaction mixture was quenched with ACS Paragon Plus Environment

Page 18 of 24

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10 % NaHCO3 solution, extracted with dichloromethane and washed with brine (2 × 10 mL). The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification of the crude product by chromatography on silica gel (EtOAc/hexane/10% Et3N) afforded γ-butyrolactone fused γ-butyrolactams 4. 6a-benzyl-3,4-diphenyltetrahydro-1H-furo[3,4-c]pyrrole-1,6(3H)-dione (4a): White solid. Yield: 71 mg (62%). Mp: 160–164 oC. 1H NMR (400 MHz, CDCl3): δ 7.42–7.40 (m, 3H), 7.19 (s, 3H), 7.14–7.08 (m, 5H), 6.98 (d, J = 4.4 Hz, 2H), 6.67 (d, J = 4.4 Hz, 2H), 5.19 (d, J = 14.4 Hz, 1H), 4.93 (d, J = 3.6 Hz, 1H), 4.68 (d, J = 8.4 Hz, 1H), 3.72 (d, J = 15.6 Hz, 1H), 3.62 (d, J = 14.8 Hz, 1H), 3.37–3.32 (m, 1H) ppm.

13

C{1H} NMR (100 MHz, CDCl3): δ 170.5, 167.0,

139.2,135.1, 134.8, 129.7, 129.3, 128.9, 128.8, 128.6, 128.5, 128.4, 128.3, 128.1, 127.7, 127.1, 124.9, 80.4, 62.2, 48.4, 46.5, 45.6 ppm. MS (ESI) m/z: 382 [M-H] +. Anal Calcd for C25H21NO3: C 78.31, H 5.52, N 3.65; Found: C 78.50, H 5.64, N 3.69. 6a-benzyl-4-phenyl-3-(p-tolyl)tetrahydro-1H-furo[3,4-c]pyrrole-1,6(3H)-dione (4b): White solid. Yield: 80 mg (67%). Mp: 176–180 oC. 1H NMR (400 MHz, CDCl3): δ 7.51-7.46 (m, 3H), 7.27–7.26 (m, 3H), 7.15 (d, J = 6.4 Hz, 2H), 7.06–7.04 (m, 2H), 7.01 (d, J = 8.0 Hz, 2H), 6.63 (d, J = 8.0 Hz, 2H), 5.27 (d, J = 14.4 Hz, 1H), 4.98 (d, J = 4.4 Hz, 1H), 4.73 (d, J = 8.8 Hz, 1H), 3.79 (d, J = 14.4 Hz, 1H), 3.69 (d, J = 14.4 Hz, 1H), 3.43–3.37 (m, 1H), 2.26 (s, 3H) ppm. 13

C{1H} NMR (100 MHz, CDCl3): δ 170.6, 167.0, 138.4, 136.2, 135.1, 134.7, 129.6, 129.4,

129.3, 128.9, 128.8, 128.1, 124.8, 80.5, 62.2, 48.5, 46.5, 45.6, 21.1 ppm. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C26H23NO3Na 420.1570; Found 420.1575.



ASSOCIATED CONTENT Supporting Information Copies of 1H and 13C NMR spectra for all products and X-ray structural information for 1f and 3m (CIF). This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding author * Fax:+91-431-2407043. Tel: +91-431-2407053. E-mail: [email protected] Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS The authors thank Science and Engineering Research Board (SERB), India for financial support and DST-FIST for instrumentation facilities at School of Chemistry, Bharathidasan University. V.J.T. thanks the University Grants Commission (UGC) for a BSR-RFSMS fellowship. NOTES AND REFERENCES (1) (a) England, D. B.; Kuss, T. D. O.; Keddy, R. G.; Kerr, M. A. Cyclopentannulation of 3Alkylindoles: A Synthesis of a Tetracyclic Subunit of the Kopsane Alkaloids. J. Org. Chem. 2001, 66, 4704–4709. (b) Yadav, V. K.; Sriramurthy, V. Formal [3+2] and [3+3] Additions of Acceptor-Substituted Cyclopropylmethylsilanes to Allenylsilanes. Org. Lett. 2004, 6, 4495– 4498. (c) Nanteuil, F.; Serrano, E.; Perrotta, D.; Waser, J. Dynamic Kinetic Asymmetric [3+2] Annulation Reactions of Aminocyclopropanes. J. Am. Chem. Soc. 2014, 136, 6239−6242. (d)


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annulation of Î³-butyrolactone fused donor-acceptor cyclopropanes

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