chapter 2b base-mediated hydroamination of...

Chapter 2B Base-Mediated Hydroamination of

Unsymmetrical Internal Alkynes

Chapter 2 Part B: Base-mediated hydroamination of unsymmetrical internal alkynes

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2B.1. INTRODUCTION AND OBJECTIVE OF THE WORK Enamines derived from secondary amines are among the most versatile intermediates in organic synthesis.1 Known as versatile enol synthons since the pioneering work of Stork,2 enamines are typically prepared by reacting a given secondary amine with an appropriate aldehyde or ketone in a condensation process, often in the presence of an acid catalyst and a water scavenger.3 This method is useful, but it also has several drawbacks such as lack of regioselectivity and low functional group tolerance. Other non-metal-catalyzed methods for the synthesis of N-alkenylamines are limited in scope due to the requirement for activated alkenyl halides.4

In a recent report by Verma et al. on the copper-catalyzed tandem synthesis of indolo- and pyrrolo [2,1-a]isoquinolines from various N-heterocycles I and ortho-alkynylarylhalides II, it was concluded that the reaction undergoes via formation of a hydroaminated intermediate I1 (Scheme 2b.1).5

Scheme 2b.1. Tandem synthesis of substituted indolo- and pyrrolo[2,1-a]isoquinolines

Hence, with the successful results of hydroamination of symmetrical internal alkynes using stoichiometric amounts of KOH, we wish to explore the reaction of unsymmetrical internal alkynes with various N-heterocycles and to check the effect of different substituents on the stereoselectivity of the product formation.6 2B.2. RESULTS AND DISCUSSION 2B.2.1. Synthesis of unsymmetrical alkynes: For the hydroamination reaction, the unsymmetrical internal alkynes were synthesized by the conventional Sonogashira reaction of commercially available aryl halides 2 and


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Table 2b.1. Synthesis of 1,2-disubstituted ethyne.a

entry alkyne 1 arylhalide 2 product 3 yield (%)b

1 1a

2a

3a

92

2 1b

2b

3b

94

3 1b 2c

3c

90

4 1b 2d

3d

89

5 1a I

I

2e

3e

92

6c 1c

2f

3f 82

7c 1b 2f 3g

86

aAll reactions were performed with 1 (1.0 mmol), 2 (1.1 equiv), 5 mol % Pd(PPh3)2Cl2, Et3N (4.0 equiv), in 2.0 mL of MeCN, at 60–70 ºC under nitrogen atmosphere. bIsolated yields. cPd(PPh3)2Cl2 (2 mol %) in THF (5 mL), Et3N (1.0 equiv), 25 ºC.

terminal alkynes 1 (Table 2b.1).7 Sonogashira coupling of 1a and 1b with 2a–e was easily achieved at 60–70 °C in the presence of 5 mol % Pd(PPh3)2Cl2, 4.0 equiv of Et3N in 2.0 mL of MeCN under nitrogen atmosphere in 89–94 % yields (Table 2b.1, entries 1–5) and the spectral data of the products 3a–e was found to be identical with the previous reports.


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Substituted alkynones were prepared by the coupling of benzoyl chloride 2f with 1c and 1b using Pd(PPh3)2Cl2 (2 mol %) in THF (5 mL) and Et3N (1.0 equiv) at 25 ºC (Table 2b.1, entries 6 and 7).7b

2B.2.2. Synthesis of Z-vinyl enamines: Hydroamination of unsymmetrical internal alkynes 3a–e with N- heterocycles 4a and 4b was done using 2.5 equiv. of KOH in 18–24 h (Table 2b.2, entries 1–6). Substituents attached to the N-heterocycle made a similar effect on the progress of the reaction as observed with symmetrical alkynes discussed before in Chapter 2a.6 3-Methylindole 4a afforded the mixture of addition products 5a and 5c with 3b and 3c in 67% and 63% yields respectively(Table 2b.2, entries 1 and 3). Similarly, pyrrole also provided 5b in 68% yield (entry 3). Reaction of 4a and 4b with ortho-haloarylhalides 3d and 3e yielded a complex mixture of cyclized and non-cyclized product which on addition of CuI and ligand BtCH2OH provided the products 5d–f in good yields (entries 4–6).

Table 2b.2. Scope of the addition of N-heterocycles on unsymmetrical alkynes

entry N-heterocycle 4 alkyne 3 product 5 yield (%)b

1 4a

3b

5a

67

2 4b

3a

5b

68

3 4a

3c

5c

63


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entry N-heterocycle 4 alkyne 3 product 5 yield (%)b

4 4a 3d

5d

82c

5 4a 3e

5e

85c

6 4b 3e

5f

84c

a The reactions were performed using N-heterocycle 1 (2.0 equiv), 1.0 mmol of the alkyne 2 and 2.5 equiv of KOH in 1.5 mL of DMSO at 120 oC for 24 h unless otherwise noted. b Total yield of two isomers. c CuI (5 mol %) and ligand / BtCH2OH (10 mol %) were added.

2B.2.3 Characterization of compound 5b: 1-(1-(4-methoxyphenyl)-2-phenylvinyl)-1H-pyrrole

The base–mediated addition of pyrrole 4b onto alkyne 3a provided a mixture of two products in 80:20 isomeric ratios as per the NMR spectral data (Figure 2b.1 and 2b.2). Out of the two possible Z-regioisomers 5b(i) and 5b(ii), the major isomer formed was difficult to make out by 1H and 13C NMR data. So, it was concluded that


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the electronic bias of the groups on both carbons of the triple bond plays an important role in the selective attack of the nucleophile.

N OMeN

MeO5b(i)Major

5b(ii)Minor

Figure 2b.1. 1H NMR of 1-(1-(4-methoxyphenyl)-2-phenylvinyl)-1H-pyrrole (5b)


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Figure 2b.2. 13C NMR of 1-(1-(4-methoxyphenyl)-2-phenylvinyl)-1H-pyrrole (5b)

DFT-B3LYP/6-31+G* calculations: Formation of the major isomer in the mixture of two possible Z-isomers was assumed to form by the preferential attack on more electrophilic alkynyl carbon Cα of 3a as per the DFT-B3LYP/6-31+G* calculations using Gausian 03 (Figure 2b.3). This was further confirmed by the cyclization of 4b and 3e to form pyrrolo[2,1-a]isoquinoline 5f which is possible only when the attack of pyrrolyl anion will take place on Cα position of 3e, more electrophilic as per the

N O MeN

Me O 5b(i) Major

5 b( ii) Minor


70

energy calculations. Formation of the cyclized product was confirmed by the 1H and 13C NMR (Figure 2b.4).

3a 3e

Figure 2b.3. Natural population analysis (B3LYP.6-31+G*)

Figure 2b.4. 1H and 13C NMR of 5-(4-methoxyphenyl)pyrrolo[2,1-a]isoquinoline (5f)


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2B.3. SYNTHESIS OF ENAMINONES

For more than a century, 1, 3- dicarbonyl compounds and their derivatives have been some of the most versatile and frequently employed C3 synthons in organic synthesis. Now a days, a wide variety of simple and complex 1, 3- dicarbonyl compounds are commercially available. Among them, enaminones have long been used in synthetic chemistry. One reason for their widespread application is their versatile reactivity, as both electrophiles and nucleophiles. Due to their value, a number of methods have been developed for the preparation of enaminones.8 For decades, enaminones are known to be prepared by the general reaction of amines and 1, 3- diketones and are established substrates in heterocyclic chemistry.9 But, the conventional methodology suffers from various drawbacks. The utilization of ynones is a common strategy in the synthesis of many biologically important compounds.10

Hydroamination of alkynones can be a powerful tool for the synthesis of enaminones and also this methodology can further be utilized for the preparation of other heterocycles (Scheme 2b.2).

Scheme 2b.2. Hydroamination of alkynones

2b.3.1. Results and Discussion

In a report on the coupling of acid chlorides with terminal alkynes using one equivalent of triethylamine under Sonogashira conditions followed by subsequent addition of amines or amidinium salts to the intermediate alkynones, corresponding enaminones and pyrimidines were synthesized under mild conditions in excellent yields by Muller and his co-workers.7b

Therefore, addition of heterocyclic amines onto alkynones using KOH was also explored. During the course of reaction of 4a and 3f, it was observed that at high temperatures a highly polar unidentified complex was formed. Thus, we carried out the reaction by using 0.2 equiv. of KOH at 80 °C. It was motivating to find that


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reaction of heterocycles 4a and 4b with alkynone 1-phenyl-3-(trimethylsilyl)prop-2-yn-1-one 3f provided E- isomers 6a and 6b as major products with the hydrolysis of TMS within 10 minutes in 81 and 76% yields respectively (Scheme 2b.3). Longer reaction time led to the decomposition of product. Intermolecular addition of heterocycle 4a and alkynone, 1-phenyl-3-p-tolylprop-2-yn-1-one 3g yielded a mixture of hydroaminated products 6c in E:Z::75:25 stereoisomeric ratios in 56% yield.

Scheme 2b.3. Addition of indoles onto alkynones

This addition of N-heterocycle onto corresponding alkynone takes place in accordance to Michael addition reaction. The hydroxide generates a nucleophile P which attacks on the electrophilic alkyne conjugated with the carbonyl group giving rise to an allene intermediate Q. This intermediate deprotonates a water molecule recreating hydroxide and the more favourable carbonyl group (Scheme 2b.3). 2b.3.2. Characterization of compound 10a: 3-(3-methyl-1H-indol-1-yl)-1-phenylprop-2-en-1-one


73

Compound 6a was prepared by the addition of 0.2 mmol of KOH in the solution of 3-methylindole 4a and 1-phenyl-3-(trimethylsilyl)prop-2-yn-1-one 3f in DMSO. The reaction mixture was heated at 80 °C for 10 min. The structure of compound 6a was established on the basis of its spectral data analysis. Its high resolution mass spectrum showed [M]+ peak at m/z 261.1153, which confirmed its molecular formula to be C17H15N. In the 1H NMR spectrum in CDCl3 at 400 MHz, the characteristic peaks of methyl group at C3' of indole ring, appeared at δ 2.25 as singlet for 3 protons. The styryl protons at C2 and C3 appeared at δ 6.89 and 8.39 ppm with a coupling constant J of 13.2 Hz suggesting that the compound formed was an E-isomer (Figure 2b.5).

N

O

Me

Hx

Hy

Hy (J = 13.4 Hz)

Hx (J = 13.4 Hz)

Figure 2b.5. 1H NMR of (E)-3-(3-methyl-1H-indol-1-yl)-1-phenylprop-2-en-1-one (6a)


74

Similarly, the 13C NMR spectrum in CDCl3 at 100 MHz (Figure 2b.6), appearance of the methyl carbon attached with C3' appeared at δ 9.8 ppm and that of carbonyl carbon C1 at δ 189.6 ppm confirmed the formation of an addition product. The peaks of all other protons and carbons of the molecule were present in 1H and 13C NMR spectra of the molecule.

Figure 2b.6. 13C NMR of (E)-3-(3-methyl-1H-indol-1-yl)-1-phenylprop-2-en-1-one (6a)

2B.4. CONCLUSION Present study on the addition of N-heterocycles onto unsymmetrical alkynes by using stoichiometric amount of KOH suggests that the copper-catalyzed tandem synthesis of indolo- and pyrrolo[2,1-a]isoquinolines occurred via formation of Z-stereoisomer formed by the selective attack of the nucleophile on more electrophilic alkynyl carbon followed by metal-catalyzed intramolecular cyclization.. For the first time, KOH have been used for the selective addition of heterocyclic amines onto alkynones under mild conditions to obtain enaminones.

2B.5. EXPERIMENTAL SECTION 2B.5.1. General procedure for hydroamination of unsymmetrical internal alkynes 3a–d: In an oven dried pressure tube, to a solution of N-heterocycle (2.0 equiv) in DMSO and finely crushed KOH (2.5 equiv), alkyne (1.0 mmol) was added. The resulting reaction mixture was heated at 120 °C. Progress of the reaction was


75

monitored by TLC, while noticing complete consumption of alkynes, reaction mixture was brought to room temperature. The reaction mixture was extracted with ethyl acetate (5 mL x 3), and evaporated under reduced pressure. The crude reaction mixture was purified using silica gel column chromatography.

2B.5.2. Analytical data

3-methyl-1-(2-phenyl-1-p-tolylvinyl)-1H-indole (5a): The product was obtained as a yellow oil: 1HNMR (300 MHz, CDCl3): δ 7.60 [(d, J = 8 Hz, 2H); 1H (for major) + 1H (for minor)], 7.32–7.21 [(m, 4H); 2H (for major) + 2H (for minor)], 7.18–7.07 [(m, 8H); 4H (for

major) + 4H (for minor)], 7.02–6.93 [(m, 6H); 3H (for major) + 3H (for minor)], 6.87 [(d, J = 3.9 Hz, 1H); 0.5H (for major) + 0.5H (for minor)], 6.84 [(d, 1H); 0.5H (for major) + 0.5H (for minor)], 6.80 [(m, 4H); 2H (for major), 2H (for minor)], 6.66 [(s, 1H); 1H (for major)], 6.53 [(d, J = 2.1 HZ, 1H ; for minor)], 5.23 [(d, J = 13.8 Hz, 1H; for major)], 2.35 [(s, 9H); 6H ( {67 %}for major) + {33 %}3H (for minor)]; 13C NMR (75 MHz, CDCl3): δ 138.8, 137.7, 136.1, 134.8, 130.1, 129.6, 128.7, 128.6, 128.3, 128.2, 127.6, 126.8, 126.3, 125.8, 125.5, 124.4, 124.1, 122.0, 119.5, 118.7, 21.3, 9.8 (for major regioisomer); and 138.3, 136.4, 135.0, 130.5, 129.9, 128.5, 128.1, 126.9, 126.1, 123.7, 119.8, 119.0, 21.5, 9.7 (for minor regioisomer). HRMS (ESI) :[M]+ Calcd for [C24H21N] : 323.1674, found : 323.1672.

1-(1-(4-methoxyphenyl)-2-phenylvinyl)-1H-pyrrole (5b): The product was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3): δ 7.36–7.32 [(m, 2H; (for major)], 7.34–7.07 [(m, 6H);

2H (for CDCl3), 3H (for major)+ 1H (for minor)], 6.91–6.84 [(m, 3H); 2.5 H (for major), 0.5 (for minor)], 6.81 [(d, J = 8.1 Hz, 2H); 2H (for major)], 6.73 [(d, J = 5.7 Hz, 2H); 2H (for major)], 6.61–6.59 [(m, 1H); 2H (for minor)], 6.58 [(t, J = 2.1 Hz, 2H); 1H (for major), 1H (for minor)], 6.33 –6.32 [(m, 1H); 1H (for major)], 6.29 [(t, J = 2.1 Hz, 2H); 2H (for major)], 3.82 [(s, 3H; ( 80% ) for major)], 3.77 [(s, 3H; (20%) for minor)]; 13C NMR (75 MHz, CDCl3): δ 164.5, 148.0, 140.6, 138.8, 131.2, 130.8, 130.0, 128.5, 128.9, 124.7, 124.5, 123.5, 120.5, 87.8, 51.6 (for major regioisomer); and 141.1, 139.6, 132.6, 128.1, 127.5, 126.3, 126.0, 125.4, 124.7, 124.3, 122.9, 117.6,


76

102.2, 87.1 (for minor regioisomer). HRMS (ESI): [M]+ Calcd for [C19H17NO] : 275.1310, found : 275.1315.

1-(2-(4-bromophenyl)-1-(p-tolyl)vinyl)-3-methyl-1H-indole

(5c): The product was obtained as a pale yellow oil . 1H NMR (300 MHz, CDCl3): δ 7.34 [dt, J = 2.3, 4.6 Hz, 1H; (for major)], 7.14 [dt, J = 2.3, 5.0 Hz, 2H; (2H for major)], 7.05-7.03 [m, 5H;

(4H for major + 1H for minor)], 7.03 [dd, J = 1.8 Hz, 1H; (for major)], 6.99 [dt, J = 1.8, 5.0 Hz, 1H; (for major)], 6.97–6.88 [m, 2H; (1H for major + 1H for minor)], 6.85 [d, J = 8.7 Hz, 1H; (for major)], 6.79–6.75 [m, 2H; (1H for major + 1H for minor)], 6.56–6.63 [m, 2H; (1H for major + 1H for minor)], 6.57 [dt, J = 2.3, 5.0 Hz, 2H; (1H for major + 1H for minor)], 2.28 [(s, 4.6 H; 3H i.e. 65% for major + 1.6 H i.e. 35% for minor)], 2.27 (s, 3 H); 13C NMR (CDCl3 , 75 MHz): δ 139.1, 137.0, 135.5, 134.0, 131.7, 131.4, 130.1, 129.1, 128.7, 127.6, 126.3, 125.5, 122.2, 121.8, 119.6, 118.8, 113.3, 111.7, 21.2, 9.7 (for major regioisomer); and 138.0, 137.8, 134.3, 131.3, 130.5, 124.8, 122.5, 122.0, 121.2, 119.1, 111.5, 21.4, 9.5 (for minor regioisomer). HRMS (ESI): [M]+ Calcd for [C24H20BrN] : 401.0779, found 401.0782.

12-methyl-6-p-tolylindolo[2,1-a]isoquinolines (5d): The product was obtained as a yellow solid, mp: 152–155 °C; 1H NMR (300 MHz, CDCl3): δ 8.43 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.44–7.39 (m, 3H), 7.35 (d, J = 7.8 Hz, 2H),

7.24 (t, J = 8.7 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.46 (t, J = 8.7 Hz, 2H), 2.89 (s, 3H), 2.52 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 139.1, 138.5, 133.9, 131.4, 130.9, 130.1, 129.6, 129.1, 128.5, 127.2, 126.6, 126.5, 126.1, 124.4, 120.9, 120.2, 117.9, 114.4, 110.8, 105.4, 21.5, 11.8. HRMS (ESI): [M]+ Calcd for [C24H19N]: 321.1517, found : 321.1517.

6-(4-methoxyphenyl)-12-methylindolo[2,1-a]isoquinoline (5e): The product was obtained as a yellow solid, mp: 155–156 °C; 1H NMR (300 MHz, CDCl3): δ 8.43 (d, J = 7.8 Hz, 1H), 7.79 (d, J =

N

Me

MeO


77

8.1 Hz, 1H), 7.54–7.39 (m, 5H), 7.26 (t, J = 9.0 Hz, 1H), 7.07 (d, J = 8.7 Hz, 2H), 6.93 (t, J = 7.5 Hz, 1H), 6.49 (d, J = 8.7 Hz, 1H), 6.43 (s, 1H), 3.94 ( s, 3H), 2.89 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 160.2, 138.2, 131.5, 130.9, 130.5, 130.2, 130.1, 129.3, 127.2, 126.7, 126.6, 126.2, 124.4, 120.9, 120.3, 118.0, 114.4, 114.3, 110.8, 105.4, 55.4, 11.8. HRMS (ESI): [M]+ Calcd for [C24H19NO]: 337.1467, found : 337.1466.

5-(4-methoxyphenyl)pyrrolo[2,1-a]isoquinolines (5f): The product was obtained as a yellow solid, mp: 142–144 °C; 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 7.8 Hz, 1H), 7.61–7.59 (m, 2H), 7.56 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 6.8 Hz, 1H), 7.35 (t, J = 8.0

Hz, 1H), 7.29–7.28 (m, 1H), 7.07–7.05 (m, 3H), 6.71 (t, J = 3.2 Hz, 1H), 6.67 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.4, 136.6, 131.1, 130.4, 127.9, 127.6, 127.2, 126.9, 125.9, 125.7, 122.1, 114.5, 114.2, 111.6, 111.4, 100.5, 55.6. HRMS (ESI): [M]+ Calcd for [C19H15NO] : 273.1154, found : 273.1155.

General procedure for the addition of N-heterocycles with alkynones: To a solution of N-heterocycle (2.0 equiv) in DMSO and finely crushed KOH (0.2 equiv), alkyne (1.0 mmol) was added. Resulting mixture was heated at 80 °C. Progress of the reaction was monitored by TLC. After the complete consumption of alkynes, reaction mixture was brought to room temperature. The reaction mixture was extracted with ethylacetate (5 mL X 3) and evaporated under reduced pressure. The crude reaction mixture was purified using silica gel column chromatography.

(E)-3-(3-methyl-1H-indol-1-yl)-1-phenylprop-2-en-1-one (6a): The product was obtained as a yellow solid, mp: 110–112 °C; 1H NMR (400 MHz, CDCl3): δ 8.39 (d, J = 13.9 Hz, 1H), 7.93 (dd, J

= 7.4, 1.4 Hz, 2H), 7.52 (d, J = 8.1 Hz, 1H), 7.51–7.47 (m, 2H), 7.45–7.39 (m, 2H), 7.26 (t, J = 8.1 Hz, 1H), 7.23–7.17 (m, 2H), 6.89 (d, J =13.2 Hz, 1H), 2.25 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 189.6, 138.7, 137.6, 136.8, 132.5, 132.4, 130.9, 128.5, 128.0, 124.8, 124.2, 122.5, 120.7, 119.6, 119.4, 111.2, 102.3, 9.8. HRMS (ESI): [M]+ Calcd for [C18H15NO] : 261.1154, found : 261.1153.


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(E)-3-(1H-indol-1-yl)-1-phenylprop-2-en-1-one (6b): The product was obtained as a light brown solid, mp: 105–108 °C; 1H

NMR (400 MHz, CDCl3): δ 8.51 (d, J = 13.9 Hz, 1H), 8.02 (d, J = 6.6 Hz, 2H), 7.67 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.58 (dt, J = 7.4, 2.2 Hz, 1H), 7.54–7.50 (m, 3H), 7.37 (t, J = 7.3 Hz, 1H), 7.28–7.24 (m, 1H), 7.09 (d, J = 13.2 Hz, 1H), 6.78 (d, J = 3.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 189.9, 138.6, 137.8, 136.4, 132.6, 129.9, 128.6, 128.1, 124.2, 123.6, 122.8, 121.6, 110.4, 109.4, 104.6. HRMS (ESI): [M]+ Calcd for [C17H13NO] : 247.0997, found : 247.0997.

3-(3-methyl-1H-indol-1-yl)-1-phenyl-3-(p-tolyl)prop-2-en-1-one (6c): The product was obtained as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.91 [dd, J = 7.3, 1.5 Hz, 0.7H; (for minor)], 7.70 [dt, J = 7.4, 1.5 Hz, 2.0H; (for major)], 7.40 [d, J = 7.3 Hz, 2.0H;

1.0 H (for major) + 1.0 (for minor)], 7.37–7.32 [m, 2H; 1.0 H (for major) + 1.0 (for minor)], 7.27–7.16 [m, 6H; 5.0 H (for major) + 1.0 (for minor)], 7.06 [t, J = 7.3 Hz, 1H; (for major)], 7.03–6.99 [m, 1H; (for major)], 6.81–6.76 [m, 3H; (for major)], 2.42 [s, 3H; (75% for major regioisomer)], 2.39 [s, 1H; (25% for minor regioisomer)], 2.29 [s, 1H; (25% for minor regioisomer)], 2.18 [s, 3H; (75% for major regioisomer)]; 13C NMR (100 MHz, CDCl3): δ 190.7, 152.0, 148.8, 141.5, 139.1, 138.5, 136.7, 134.1, 132.4, 132.1, 130.1, 129.6, 129.3, 128.6, 128.4, 127.9, 127.8, 125.8, 122.3, 120.4, 118.9, 114.4, 112.9, 21.5, 9.6 (for major regioisomer); and 190.8, 140.6, 138.5, 136.7, 132.2, 131.6, 130.3, 127.0, 123.0, 121.4, 119.4, 115.3, 114.1, 112.5, 21.4, 9.5 (for minor regioisomer). HRMS (ESI): [M-1]+ Calcd for [C25H21NO]: 351.1623, found : 351.1622.

NOTE: All the data mentioned here has been published in Org. Lett. 2011, 13, 1630 and J. Org. Chem. 2012, Manuscript jo-2012-00782n (Revisions submitted to Editorial Office). Therefore, selected spectras has been added in Appendix-II to avoid wastage of paper.

O

N

Me

Me


79

2B.6. REFERENCES 1. Rappoport, Z. In The Chemistry of Enamines; Wiley & Sons: New York,

1994, Vol. 2. 2. Stork, G.; Szmuszkovicz, J.; Terrell, R.; Brizzolara, A.; Landesman, H. J. Am.

Chem. Soc. 1963, 85, 207. 3. Hickmott, P. W. Tetrahedron 1982, 38, 1975. 4. (a) Dalili, S.; Yudin, A. K. Org. Lett. 2005, 7, 1161. (b) De Ancos, B.;

Maestro, M. C.; Martin, M. R.; Farina, F. Synthesis 1988, 136. (c) Cebulska, Z.; Laurent, A. J.; Laurent, E. G. J. Fluor. Chem. 1996, 76, 177.

5. Verma, A. K.; Kesharwani, T.; Singh, J.; Tandon, V.; Larock, R. C. Angew. Chem. Int. Ed. 2009, 48, 1138.

6. (a) Verma, A. K.; Joshi, M.; Singh, V. P. Org. Lett. 2011, 13, 1630. (b) Joshi, M.; Patel, M.; Tiwari, R.; Verma, A. K. J. Org. Chem. 2012, Manuscript jo-2012-00782n (Revisions submitted to Editorial Office).

7. (a) Park, K.; Bae, G.; Moon, J.; Choe, J.; Song,K. H.; Lee, S. J. Org. Chem. 2010, 75, 6244. (b) Karpov, A. S.; Muller, T. J. J. Org. Lett. 2003, 5, 3451.

8. (a) Dixon, K.; Greenhill, J. V. J. C. S. Perkin I, 1974, 164. (b) Greenhill, J. V. J.C.S. Perkin I, 1976, 2207. (c) Dixon, K.; Greenhill, J. V. J.C.S. Perkin I 1976, 2211.

9. For reviews on the enaminones in organic syntheses (a) Smirnova, Y. V.; Krasnaya, Z. A. Russ. Chem. Rev. 2000, 69, 1021. (b) Michael, J. P.; De Koning, C. B.; Gravestock, D.; Hosken, G. D.; Howard, A. S.; Jungmann, C. M.; Krause, R. W. M.; Parsons, A. S.; Pelly, S. C.; Stanbury, T. V. Pure Appl. Chem. 1999, 71, 979.

10. (a) Lue, P.; Greenhill, J. V. Adv. Heterocycl. Chem. 1997, 67, 207. (b) Cimarelli, C.; Palmieri, G. Recent. Res. Devel. Org. Chem. 1997, 1, 179. (c) Michael, J. P.; Gravestock, D. Pure. Appl. Chem. 1997, 69, 583. (d) Greenhill, J. V. Chem. Soc. Rev. 1977, 6, 277.

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