Jhaumeer-Laulloo Sabina* Department of Chemistry, University of - - PowerPoint PPT Presentation

Authors: Moosun Bibi Salma Bhowon Gupta Minu Bhewa Shabneez Jhaumeer-Laulloo Sabina* Department

• f

Chemistry, University

• f

Mauritius * Corresponding author: sabina@uom.ac.mu

The construction of new C-C bonds is of central importance in Organic Chemistry for the assembly of complex molecular frameworks with diversified interests and applications such as: Development of new Drugs, Industrial Chemical Processes, Synthesis of Pharmaceuticals, Biologically Active Compounds, Natural product synthesis and Material chemistry.

The emergence of cross-coupling as a popular method in synthesis arises from the diversity of transition metal complexes which have been developed and used successfully as catalysts in these reactions. Among the ones used, Palladium occupy a unique position since: Facile decomposition to Pd(0). Cheaper than platinum. High recovery of palladium catalyst.

Russell, M. J. H, Platinum Met. Rev. 1989, 33, 186

Palladium phosphine complexes that have been used in C-C bond formations (Heck & Suzuki):

Pd

Ph2 P PPh2 P Ph2 PPh2 O X (Sabounchei & Ahmadi, 2013)

N N

Pd

PPh2 OAc

(Liu et al, 2014)

Pd PPh3 Ph3P OAc AcO

(Amotore et al, 1994)

Drawbacks of palladium phosphine complexes: Expensive Air sensitive. Unstable. Sometimes precipitate. Therefore the need to develop cheaper and more stable palladium-based catalysts.

The C-C coupling reactions that have been studied in this work: Heck, Suzuki and Michael Addition reactions.

[Pd4(dbbs)4] (1) [Pd(dpds)Cl] (2)

(dbbs)2 = N,N'-(1,1'-dithio-bis(phenylene))bis(salicylideneimine) (dpds)2 = o,o’-(N,N’-dipicolinyldene)diazadiphenyl disulfide)

In this work, palladium complexes (1) and (2) derived from Schiff Base ligands have been used as catalyst for cross coupling reactions

Moosun, S. B., Bhowon, M. G., Hosten, E. C., Jhaumeer-Laulloo, S. J. Coord. Chem. 2016

It involves the coupling of an aryl, vinyl halide or sulfonate with an alkene.

R-X + R' R' R catalyst base

• HX

I + O O O O Catalyst Base/Solvent Methyl cinnamate

The cross coupling of iodobenzene with methyl acrylate was investigated. The formation of the methyl cinnamate was confirmed by 1H NMR and GC/MS data

4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 ppm 3.813 6.416 6.480 7.261 7.391 7.402 7.522 7.536 7.548 7.671 7.735

3.00 1.01 2.97 2.02 1.03

• Fig. 1.0: 1H NMR spectrum of methyl cinnamate

5.11 5.61 6.11 6.61 7.11 7.61 8.11 8.61 9.11 9.61 10.11 10.61 11.11 11.61 12.11 Time 100 % Pd paps NEt3 24h 2nd 2 1: Scan EI+ TIC 2.13e10 6.96 9.98 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 m/z 100 % PdOH Na2CO3 24 3 904 (9.985) 1: Scan EI+ 1.49e9 71.0371 57.0835 43.0490 41.0226 29.0052 28.0638 85.0553 99.0662 113.1428 127.2133 155.1226 169.1787 197.2079 254.2430 211.2540

25 35 45 55 65 75 85 95 105 115 125 135 145 155 165 m/z 100 % PdOH Na2CO3 24 3 532 (6.950) 1: Scan EI+ 2.50e9

161.8988 130.8924 102.9650 76.9632 51.0078 49.9227 29.0052 38.9961 76.0238 63.0130 101.9542 91.0505 78.0471 104.0479 117.1120 160.9618 132.0466 147.0474 133.1285 163.0522

Methyl cinnamate Octadecane (a) (b) (c)

• Fig. 2.0: (a) GC chromatogram of methyl cinnamate and octadecane; (b) Mass

spectrum of octadecane; (c) Mass spectrum of methyl cinnamate.

The reaction conditions were systematically optimized in the standard reaction of iodobenzene with methyl acrylate using catalyst 1. The parameters that were being investigated are: Time, Solvent, Base Catalyst loading.

100 5 24 48 69

% Yield Time (h)

Time Effect Optimization of reaction conditions between iodobenzene and methyl acrylate: 120 °C, 1, DMF (10 mL), Na2CO3. % Yield was determined by GC-MS. Octadecane was used as internal standard.

Time (h) % Yield 5 24 99 48 84 69 70

Time Effect: Maximum conversion was obtained at 24h. A steady decrease in yield was observed after 24h.

100 0.0025 0.0052 0.0075

% Yield

Catalyst (mMol)

Catalyst loading Effect

Catalyst (mMol) % Yield 0.0025 74 0.0052 96 0.0075 99

Catalyst loading effect: > 99 % conversion achieved with 0.0075 mMol.

100 Na2CO3 K2CO3 Et3N NaOAc

% Yield Bases

Base Effect

100 DMF DMA CH3CN Toluene

% Yield Solvent

Solvent effect Base % Yield Na2CO3 96 K2CO3 99 Et3N 97 NaOAc 25

Base effect: Both organic and inorganic bases were found to be very efficient except NaOAc. K2CO3 was used for further studies.

Solvent % Yield DMF 96 DMA 87 CH3CN Toluene

Solvent effect: CH3CN and toluene were inefficient. DMF was used for further reactions.

Entry X Catalyst % Conversion 1 I 1 > 99 2 Cl 1 Trace 3 Br 1 Trace 4 I

• 5

I PdCl2 3 6 I 2 98 Evaluation of halide groups and catalyst in Heck reactions

X

+

O O O O

Catalyst K2CO3/DMF 120 °C

Aryl halide: 3.0 mmol; methyl acrylate: 8.32 mmol, catalyst: 0.0052 mmol, base: 4.5 mmol; time: 24 h. Octadecane was used as internal standard. % conversion was determined by GC-MS as an average of two injections.

With chloro and bromo benzene, trace amount of product was obtained. With iodo benzene- in absence of catalyst, no Heck product formed while with PdCl2 only, trace amount obtained. Complexes 1 and 2 showed comparable yields, The scope of the reaction was further evaluated using various aryl halides and catalysts.

Suzuki reaction is the cross-coupling of an aryl or vinyl boronic acid with aryl or vinyl halide or triflate and allows the synthesis

• f conjugated olefins, styrenes, and biphenyls.

Preliminary studies were carried out using complexes 1 and 2 and further investigation is still under process.

X

+

B(OH)2

Catalyst Na2CO3 iso-propanol X = I or Br

Biphenyl

5.01 7.01 9.01 11.01 13.01 15.01 17.01 19.01 21.01 23.01 25.01 27.01 29.01 Time 100 % Biphenyl std 2: Scan EI+ TIC 6.17e8

10.42

34

21 31 41 51 61 71 81 91 101 111 121 131 141 151 161 m/z 100 % Biphenyl std 635 (10.410) 2: Scan EI+ 7.43e7

154.1895 50.9757 38.8972 26.8882 37.9568 31.9526 39.9099 153.1797 75.9908 63.0512 61.9667 73.9670 65.0033 152.1698 77.0027 102.0024 86.9033 78.0145 115.0740 151.2320 128.1411 139.1832 155.1272

• Fig. 3.0: (a) GC chromatogram of biphenyl; (b) Mass spectrum of biphenyl.

Table 2: Evaluation of halide groups and catalyst in Suzuki reactions

Entry X Catalyst % Conversion 1 I 1 97 2 Br 1 60 3 I 2 99 4 Br 2 64 Aryl halide: 0.01 mol; acid: 0.01 mol, catalyst: 0.1 mmol, base: 0.2 M; time: 6 h.

Suzuki reactions were carried out for 6 h under refluxing conditions with iodo and bromo as aryl halides. % conversion was determined after isolation of products. Moderate to excellent yields were obtained. Both catalysts were very efficient since high % conversion were

• btained (entry 1 and 3).

The bond strength of C-X influences the yield of the reaction.

It involves a nucleophilic attack of carbanions to α,β-unsaturated carbonyl compounds under basic (for deprotonation of donor) or acidic medium (activation of acceptor) in organic solvents. In the base catalysed reactions, the donor is first deprotonated forming an enolate anion which then reacts with the acceptor in a 1,4- fashion.

O + CH2(CO2CH2CH3)2 O CO2CH2CH3 CO2CH2CH3

K2CO3 Catalyst THF

24 34 44 54 64 74 84 94 104 114 124 134 144 154 164 174 184 194 204 214 224 234 244 m/z 100 % 6.87e8

160.0300 28.8714 27.8542 133.0812 55.0606 38.9640 82.9923 68.0215 113.0327 95.0584 105.0223 123.0592 141.0818 161.0384 197.0409 185.0180 168.0245 198.0487 214.0296 241.9596

• Fig. 4.0: Mass spectrum of Michael adduct

M+

The use of catalysts of 1 and 2 in the Michael reactions

• f cyclopentenones with diethymalonates in THF at

different temperatures (24-60 °C) did not gave the desired product as confirmed by the mass spectrum below.

18 28 38 48 58 68 78 88 98 108 118 128 138 148 158 168 178 188 198 208 218 228 238 248 258 m/z 100 % 1.82e9

27.5728 26.1257 132.0902 83.0127 28.2240 55.1249 39.0742 82.0739 68.9995 99.1138 127.1129 122.2793 133.1001 157.0419 153.0043 183.0641 158.0513 184.0731 214.1203 251.8648

• Fig. 5.0: Mass spectrum of Michael adduct using catalysts 1 and 2

Both palladium complexes were found to be efficient catalysts in promoting the Heck and Suzuki reactions. The products were obtained in excellent yields even at a very low catalyst loading. The yields of the product were highly dependent on parameters such as time, solvent, base and substrate. Both catalysts gave comparable yields, however catalyst 2 was better than 1, considering its lower palladium content. The complexes were inefficient as catalysts in Michael addition reactions.