Application of cu MOF 74, Cu2(OBA)2(BPY), MOF 235 as catalysts for carbon heteroatom bond forming reactions

VIETNAM NATIONAL UNIVERSITY – HO CHI MINH CITY HO CHI MINH UNIVERSITY OF TECHNOLOGY TRAN BOI CHAU APPLICATION OF Cu-MOF-74, Cu2(OBA)2(BPY), MOF-235 AS CATALYSTS FOR CARBON−HETEROATOM BOND FORMING REACTIONS PhD THESIS HO CHI MINH CITY, 2020 VIETNAM NATIONAL UNIVERSITY – HO CHI MINH CITY HO CHI MINH UNIVERSITY OF TECHNOLOGY TRAN BOI CHAU APPLICATION OF Cu-MOF-74, Cu2(OBA)2(BPY), MOF-235 AS CATALYSTS FOR CARBON−HETEROATOM BOND FORMING REACTIONS Major: Chemical Engineering Major code: 62520301 Independent examiner 1: Independent examiner 2: Assoc Prof Dr Tran Ngoc Quyen Assoc Prof Dr Ton That Quang Examiner 1: Prof Dr Phan Dinh Tuan Examiner 2: Assoc Prof Dr Nguyen Phuong Tung Examiner 3: Assoc Prof Dr Nguyen Quang Long ADVISORS: Prof Dr Phan Thanh Son Nam Assoc Prof Dr Truong Vu Thanh DECLARATION OF ORIGINALITY I hereby declare that this is my own research study The research results and conclusions in this thesis are true, and are not copied from any other resources The literature references have been quoted with clear citation as requested Thesis author Tran Boi Chau i TÓM TẮT LUẬN ÁN Luận án nhằm khảo sát hoạt tính xúc tác Cu-MOF-74, Cu2(OBA)2(BPY) MOF235 cho phản ứng hình thành liên kết carbondị tố Nội dung luận án trình bày thành bốn chương: Chương 1: Tổng quan Cu-MOF-74, Cu2(OBA)2(BPY), MOF-235 phản ứng hình thành liên kết carbondị tố Chương trình bày ưu, nhược điểm vật liệu khung kim (MOFs) ứng dụng làm xúc tác; hoạt tính xúc tác vật liệu xốp, khung hữu tâm đồng tâm sắt cho phản ứng hình thành liên kết carbondị tố tổng hợp aryl ethers hợp chất dị vòng cạnh, cạnh ngưng tụ với vòng benzene Đồng thời, chương nêu tóm tắt phương pháp tổng hợp, đặc trưng hóa lý số ứng dụng ba loại vật liệu Cu-MOF-74, Cu2(OBA)2(BPY), MOF-235 Chương 2: Trình bày thực nghiệm kết phân tích đặc trưng cấu trúc Cu-MOF-74, Cu2(OBA)2(BPY), MOF-235 Các loại vật liệu tổng hợp phương pháp nhiệt dung mơi phân tích đặc trưng hóa lý phương pháp nhiễu xạ tia X dạng bột (P-XRD), phổ hồng ngoại (FT-IR), kính hiển vi điện tử quét (SEM), kính hiển vi điện tử truyền qua (TEM), đo diện tích bề mặt phương pháp hấp phụ đẳng nhiệt nitrogen, phương pháp nhiệt trọng lượng (TGA) Chương 3: Trình bày kết khảo sát bàn luận hoạt tính xúc tác Cu-MOF74 cho phản ứng ether hóa trực tiếp N-(quinolin-8-yl)benzamides với alcohols/phenols Hoạt tính xúc tác MOF-235 cho phản ứng oxy hóa cộng vịng benzyl alcohols 2-aminophenols/2-aminothiophenols Hoạt tính xúc tác Cu2(OBA)2(BPY) phản ứng tổng hợp quinazolines, 4H-3,1-benzoxazines Các phản ứng khảo sát tính dị thể tái sử dụng xúc tác điều kiện phản ứng Chương 4: Trình bày tóm tắt kết đạt đóng góp luận án, đồng thời đề xuất số hướng nghiên cứu ii ABSTRACT Metal–organic frameworks (MOFs) are a well-known class of materials having the potential to become homo-hetero bridge Compared with homogeneous catalysts, MOF catalysts can be recycled and reutilized for several times; while compared with conventional heterogeneous catalysts, MOFs have structural and chemical tunability Metalorganic frameworks based on copper or iron metal sites have been used as catalysts for carbonheteroatom bond forming reactions These copper-based MOFs or iron-based MOFs are promising owing to the utilization of non-precious and less toxic metal salt species Herein; Cu-MOF-74, Cu2(OBA)2(BPY), MOF-235 were synthesized by solvothermal method, and characterized by P-XRD, SEM, TEM, TGA, FT-IR, nitrogen physisorption measurements Catalytic activities of these MOFs were investigated through carbonheteroatom bond forming reactions In fact, Cu-MOF-74 was used as a catalyst for the direct etherification of N-(quinolin-8-yl)benzamides with alcohols/phenols Besides, the synthesis of some N,N-, N,O-, N,S-heterocyclic compounds was studied via two approaches One approach was based on the oxidative cyclization reaction between 2-aminophenols/2-aminothiophenols and alcohols catalyzed by MOF-235 The other was a one-pot, two-step process which involved the condensation of aldehydes with 2-aminobenzylamines/2-aminobenzyl alcohols/ 1,2phenylenediamines in catalyst-free conditions, followed by oxidative dehydrogenation of CN bond catalyzed by Cu2(OBA)2(BPY) All the surveyed catalysts were examined for the heterogeneity and reutilization under reaction conditions To the best of our knowledge, these transformations under the studied reaction conditions have not been previously mentioned iii ACKNOWLEDGMENT This thesis has been carried out at Ho Chi Minh University of Technology since 2014 It may not be a very long time for someone else, but it will always be the suffering time as well as the best time in my life I have never ever thought that I could get through this tough time in life Fortunately, there always are my warmhearted and enthusiastic scientific advisors accompanying with me to my success The motivation of them always cheer me up at the right time and help me to go ahead to the final target I can never give enough my thanks to Prof Dr Phan Thanh Son Nam and Assoc Prof Dr Truong Vu Thanh It is impossible to recount all supports from my advisors, but these will be in my heart for the remaining of my life It is an absolute misstep if I could not give my grateful thanks to Assoc Prof Dr Pham Thanh Quan, Assoc Prof Dr Le Thi Hong Nhan, Dr Phan Thi Hoang Anh All my lecturers are so kindness to boost me up whenever I got troubles to conduct the thesis or even some problems happened in personal life Additionally, I would like to send my great thanks to all friends that I met in the laboratory for their excellent helps during the period of carrying experiments I give my sincerely thanks to Ha Quang Hiep, Doan Hoai Son, Duong Ngoc Tan Xuan, To Anh Tuong, Dang Van Hieu Among these friends, Ha Quang Hiep was the first person I met in the lab, who not only instructed me the lab instruments but also helped me close the gap between me with others Finally, I would like to express my profound gratitude to my parents and also to my partner for providing me perfect support and encouragement during the entire course even in the hard time of writing this thesis Tran Boi Chau iv TABLE OF CONTENTS 1.1 Introduction to metalorganic frameworks 1.1.1 Possibility of catalytic application of MOFs 1.1.1.1 Limitations of MOFs as catalysts 1.1.1.2 The prospects of MOFs as catalysts 1.1.2 Factors affecting catalytic activities of MOFs 1.1.2.1 Influence of synthetic methods 1.1.2.2 Influence of ligands on catalytic performances 1.1.2.3 Influence of secondary building units 1.1.2.4 Influence of reaction solvents .8 1.2 MOF-235, Cu-MOF-74 and Cu2(OBA)2(BPY) 1.2.1 Synthesis, structure and physicochemical properties of MOF-235 1.2.2 Synthesis, structure and physicochemical properties of Cu2(OBA)2(BPY) 10 1.2.3 Synthesis, structure and physicochemical properties of Cu-MOF-74 11 1.3 Carbonheteroatom bond forming reactions for the synthesis of benzo-fused heterocycles 14 1.4 Carbonheteroatom bond forming reactions for the synthesis of aryl ethers 23 1.5 Aims and projects 29 2.1 Introduction 32 2.2 Experimental 32 v 2.2.1 Materials and instrumentation 32 2.2.2 Synthesis of Cu-MOF-74 33 2.2.3 Synthesis of Cu2(OBA)2(BPY) 33 2.2.4 Synthesis of MOF-235 34 2.3 Results and discussion 35 2.3.1 Characterization of Cu2(OBA)2(BPY) 35 2.3.2 Characterization of Cu-MOF-74 38 2.3.3 Characterization of MOF-235 40 2.4 Summary 43 3.1 Introduction 46 3.2 Experimental 48 3.2.1 Catalytic activity of MOF-235 for the synthesis of N,O- and N,SHeterocycles 48 3.2.1.1 Typical experiment .48 3.2.1.2 Materials and instruments 48 3.2.2 Catalytic activity of Cu2(OBA)2(BPY) for the synthesis of N,N- and N,OHeterocycles 49 3.2.2.1 Typical experiment .49 3.2.2.2 Materials and instruments 50 3.2.3 Catalytic activity of Cu-MOF-74 for the synthesis of aryl ethers 50 3.2.3.1 Typical experiment .50 3.2.3.2 Materials and instruments 51 3.3 Results and discussion 52 3.3.1 Catalytic activity of MOF-235 for the synthesis of N,O- and N,SHeterocycles 52 3.3.2 Catalytic activity of Cu2(OBA)2(BPY) for the synthesis of N,N- and N,OHeterocycles 64 3.3.3 Catalytic activity of Cu-MOF-74 for the synthesis of aryl ethers 73 3.4 Summary 84 vi 4.1 Thesis summary 86 4.2 Contribution of this thesis 87 4.3 Future works 87 vii LIST OF FIGURES Figure 1.1 Schematic presentation for the construction of typical coordination polymers/MOFs from molecular building blocks [9] Figure 1.2 Typical curves observed in hot filtration test Figure 1.3 Different type of MOF active sites, including metal nodes, functionalized organic linkers, and guest species in the pores [31] Figure 1.4 The XRD patterns and the corresponding SEM images for the ZIF-8 samples synthesized by different methods (spray drying: ZIF-8-SP, microwave: ZIF-8-MW, room temperature: ZIF-8-RT, solvothermal: ZIF-8-SV) [32] Figure 1.5 (a) Inorganic building unit of MOF-235; (b) Single-crystal X-ray structure of MOF-235 (Fe, blue; O, red; Cl, teal; C, gray) [47] Figure 1.6 Coordination environment of copper in Cu2(OBA)2(BPY) [47] 10 Figure 1.7.(a) 2D helical layers produced by Cu(II) and OBA ligands; (b) The 3D pillared-layer structure of Cu2(OBA)2(BPY) [47] 11 Figure 1.8 (a) Coordination environment of Cu(II) centers in Cu-MOF-74 after thermal solvent removal (b) Inorganic SBUs crystalline framework (c) 3D honeycomb structure of Cu-MOF-74 (Cu, blue; O, red; C, gray) [52-54] 12 Figure 1.9 Two possible paths for the conversion of amidine [86] 16 Figure 1.10 A model of pillared-grid MOFs where circles indicate bimetal paddlewheels, red lines represent grid-forming ligands and blue lines represent pillar ligands [118] 27 Figure 1.11 (a) Amino-functionalized tetracarboxylate ligand (b) Large spherical cages with diameter about 11 Å (c) Topology of [Cu6(L)3(H2O)6].(14DMF).9(H2O) (d) Unsaturated coordination space in MOF [121] 28 Figure 2.1 P-XRD of the Cu2(OBA)2(PBY) 35 Figure 2.2 FT-IR spectra of (a) the Cu2(OBA)2(BPY), (b) H2OBA, (c) 4,4’-bipyridine 36 Figure 2.3 (a) SEM, (b) TEM micrographs of the Cu2(OBA)2(BPY) 36 Figure 2.4 (a) Nitrogen adsorption/desorption isotherm, (b) Pore size distribution of the Cu2(OBA)2(BPY) 37 Figure 2.5 TGA analysis of the Cu2(OBA)2(BPY) 37 Figure 2.6 (a) P-XRD, (b) SEM micrograph, (c) TEM micrograph of the synthesized Cu-MOF-74 38 viii Figure C.15 1H-NMR spectrum of 2-(2-methoxyphenoxy)-N-(quinolin-8yl)benzamide 188 O N H O N OMe Figure C.16 13C-NMR spectrum of 2-(2-methoxyphenoxy)-N-(quinolin-8yl)benzamide Characterization data for 2-(2-methoxyphenoxy)-N-(quinolin-8-yl)benzamide (Table 3.3, entry 9) Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate = 7:1), white solid, 76% yield 1H- NMR (500 MHz, CDCl3, ppm) δ 12.27 (s, 1H), 9.01 (dd, J = 7.5, 1.0 Hz, 1H), 8.42 (dd, J = 4.0, 1.5 Hz, 1H), 8.33 (dd, J = 8.0, 2.0 Hz, 1H), 8.10 (dd, J = 8.0, 1.5 Hz, 1H), 7.58 (t, J=8 Hz, 1H), 7.49 (dd, J = 8.0, 1.0 Hz, 1H), 7.37 (ddd, J = 8.0, 7.5, 1.5 Hz, 1H), 7.32 (m, 2H), 7.26 (m, 1H), 7.19 (td, J = 7.5, 1.0 Hz, 1H), 7.06 (m, 2H), 6.79 (dd, J = 8.5, 1.0 Hz, 1H), 3.75 (s, 3H) 13 C-NMR (125 MHz, CDCl3, ppm) δ 163.7, 156.8, 152.1, 148.1, 143.8, 139.4, 136.1, 135.8, 132.8, 132.2, 128.1, 127.6, 126.2, 123.7, 122.9, 122.7, 121.5, 121.5, 121.4, 117.3, 115.9, 114.3, 56.2 189 O N H O N I Figure C.17 1H-NMR spectrum of 2-(4-iodophenoxy)-N-(quinolin-8-yl)benzamide 190 O N H O N I Figure C.18 13C-NMR spectrum of 2-(4-iodophenoxy)-N-(quinolin-8-yl)benzamide Characterization data for 2-(4-iodophenoxy)-N-(quinolin-8-yl)benzamide (Table 3.3, entry 10) Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate=7:1), white solid, 59% yield 1H-NMR (500 MHz, CDCl3, ppm) δ 12.04 (s, 1H), 8.97 (dd, J = 7.5, 1.0 Hz, 1H), 8.59 (dd, J = 4.0, 1.5 Hz, 1H), 8.38 (dd, J = 8.0, 1.5 Hz, 1H), 8.13 (dd, J = 8.0, 1.0 Hz, 1H), 7.69 (m, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.49 (m, 2H), 7.40 (dd, J = 8.0, 4.0 Hz, 1H), 7.31 (m, 1H), 7.02 (m, 3H) 13C-NMR (125 MHz, CDCl3, ppm) δ 163.0, 156.3, 154.7, 148.2, 139.2, 139.0, 136.3, 135.4, 133.2, 132.7, 128.1, 127.6, 125.5, 121.8, 121.7, 118.9, 117.3, 87.4 191 Figure C.19 1H-NMR spectrum of 2-(4-nitrophenoxy)-N-(quinolin-8-yl)benzamide 192 Figure C.20 13C-NMR spectrum of 2-(4-nitrophenoxy)-N-(quinolin-8-yl)benzamide Characterization data for 2-(4-nitrophenoxy)-N-(quinolin-8-yl)benzamide (Table 3.3, entry 11) Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate=7:1), white solid, 70% yield 1H-NMR (500 MHz, CDCl3, ppm) δ 11.67 (s, 1H), 8.93 (dd, J = 7.5, 1.0 Hz, 1H), 8.66 (d, J = 4.0 Hz, 1H), 8.38 (dd, J = 7.5, 1.5 Hz, 1H), 8.23 (d, J = 8.0 Hz, 2H), 8.15 (d, J = 8.5 Hz, 1H), 7.56 (m, 3H), 7.44 (m, 2H), 7.26 (m, 2H), 7.15 (d, J = 8.0 Hz, 1H) 13C-NMR (125 MHz, CDCl3, ppm) δ 162.5, 162.1, 152.8, 148.2, 143.6, 139.0, 136.5, 135.0, 133.5, 132.9, 128.2, 127.6, 127.0, 126.1, 126.0, 122.1, 121.8, 120.9, 118.3, 117.4 193 O NH Cl O N Figure C.21 1H-NMR spectrum of 4-chloro-2-ethoxy-N-(quinolin-8-yl)benzamide 194 O NH Cl O N Figure C.22 13C-NMR spectrum of 4-chloro-2-ethoxy-N-(quinolin-8-yl)benzamide Characterization data for 4-chloro-2-ethoxy-N-(quinolin-8-yl)benzamide (Table 3.3, entry 12) Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate=7:1), colorless solid, 86% yield 1HNMR (500 MHz, CDCl3, ppm) δ 11.96 (s, 1H), 9.06 (d, J = 7.5 Hz, 1H), 8.83- 8.81 (m, 1H), 8.29 (d, J = 8.5 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.46 (dd, J = 8.0, 4.0 Hz, 1H), 7.10 (dd, J = 7.5, 2.0 Hz, 1H), 7.06- 7.05 (m, 1H), 4.36 (q, J = 7.0 Hz, 2H), 1.77 (t, J = 7.0 Hz, 3H) 13C-NMR (125 MHz, CDCl3, ppm) δ 163.1, 157.7, 147.9, 139.4, 138.9, 136.4, 135.8, 133.9, 128.2, 127.7, 121.9, 121.6, 121.5, 121.2, 117.9, 113.0, 65.9, 15.0 195 O NH MeO O N Figure C.23 1H-NMR spectrum of 2-ethoxy-4-methoxy-N-(quinolin-8-yl)benzamide 196 O NH MeO O N Figure C.24 13C-NMR spectrum of 2-ethoxy-4-methoxy-N-(quinolin-8-yl)benzamide Characterization data for 2-ethoxy-4-methoxy-N-(quinolin-8-yl)benzamide (Table 3.3, entry 13) Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate = 7:1), white solid, 63% yield 1H-NMR (500 MHz, CDCl3, ppm) δ 11.97 (s, 1H), 9.09 (d, J = 7.5 Hz, 1H), 8.82 (dd, J = 4.0, 1.0 Hz, 1H), 8.34 (d, J = 9.0 Hz, 1H), 8.17 (dd, J = 8.5, 1.5 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.45 (dd, J = 8.5, 4.5 Hz, 1H), 6.66 (dd, J = 8.5, 2.0 Hz, 1H), 6.58 (d, J = 2.5 Hz, 1H), 4.35 (q, J = 7.0 Hz, 2H), 3.88 (s, 3H), 1.78 (t, J = 7.0 Hz, 3H) 13 C-NMR (125 MHz, CDCl3, ppm) δ 164.0, 163.8, 158.7, 147.8, 139.4, 136.4, 136.3, 134.4, 128.3, 127.8, 121.5, 121.4, 117.8, 115.7, 105.5, 99.5, 65.4, 55.7, 15.2 197 O Br NH O N Figure C.25 1H-NMR spectrum of 5-bromo-2-ethoxy-N-(quinolin-8-yl)benzamide 198 O Br NH O N Figure C.26 13C-NMR spectrum of 5-bromo-2-ethoxy-N-(quinolin-8-yl)benzamide Characterization data for 5-bromo-2-ethoxy-N-(quinolin-8-yl)benzamide (Table 3.3, entry 14) Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate = 7:1), white solid, 52% yield 1H-NMR (500 MHz, CDCl3, ppm) δ 10.01 (s, 1H), 9.06 (dd, J = 7.5, 1.0 Hz, 1H), 8.83 (dd, J = 4.0, 1.5 Hz, 1H), 8.47 (d, J = 3.0 Hz, 1H), 8.18 (dd, J = 8.0, 1.5 Hz, 1H), 7.61- 7.54 (m, 3H), 7.47 (dd, J = 8.0, 4.0 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 4.37 (q, J = 7.0 Hz, 2H), 1.75 (t, J = 7.0 Hz, 3H).13C-NMR (125 MHz, CDCl3, ppm) δ 162.6, 156.3, 150.0, 139.4, 136.4, 135.7, 135.4, 128.3, 127.7, 124.4, 122.0, 121.6, 118.0, 114.4, 113.8, 65.9, 15.1 199 Me O NH O N Figure C.27 1H-NMR spectrum of 2-ethoxy-6-methyl-N-(quinolin-8-yl)benzamide Characterization data for 2-ethoxy-6-methyl-N-(quinolin-8-yl)benzamide (Table 3.3, entry 15) Prepared as shown in the general experimental procedure and purified on silica gel (hexane: ethyl acetate = 7:1), colorless solid, 58% yield 1H-NMR (500 MHz, CDCl3, ppm) δ 10.21 (s, 1H), 9.01 (d, J = 7.5 Hz, 1H), 8.76 (dd, J = 4.0, 1.0 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.44 (dd, J = 8.5, 4.0 Hz, 1H), 7.27 (t, J = 8.0 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 4.11 (q, J = 7.0 Hz, 2H), 2.47 (s, 3H), 1.31 (t, J = 7.0 Hz, 3H) This compound is known* Y Hu, M Wang, P Li, H Li, and L Wang, "A highly efficient copper‐catalyzed C(sp2)H alkoxylation of the benzamide enabled by a bidendate directing group," Asian Journal of Organic Chemistry, vol 8, no 1, pp 171-178, 2019 200 O NH N Figure C.28 1H-NMR spectrum of N-(quinolin-8-yl)benzamide 201 O NH N Figure C.29 13C-NMR spectrum of N-(quinolin-8-yl)benzamide Characterization data for N-(quinolin-8-yl)benzamide Prepared as shown in the general experimental procedure and purified by silica gel column chromatography (hexane: ethyl acetate=7:1), white solid, 90% yield 1H-NMR (500 MHz, CDCl3, ppm) δ 10.76 (s, 1H), 8.95 (dd, J = 7.5, 1.0 Hz, 1H), 8.86 (dd, J = 4.0, 1.5 Hz, 1H), 8.20 (dd, J = 8.5, 1.5 Hz, 1H), 8.10- 8.09 (m, 2H), 7.62- 7.54 (m, 5H), 7.49 (dd, J = 8.5, 4.0 Hz, 1H) 13C-NMR (125 MHz, CDCl3, ppm) δ 165.7 148.4, 138.9, 136.6, 135.3, 134.8, 132.0, 128.9, 128.2, 127.7, 127.5, 121.8, 116.8 This compound is known* * C Wu et al., "Copper-catalyzed regioselective C–H iodination of aromatic carboxamides," Synlett, vol 27, no 06, pp 868-875, 2016 202 ... CHARACTERIZATION OF MOF2 35, Cu2 (OBA)2(BPY), Cu- MOF- 74 Cu2 (OBA)2(BPY) MOF- 235 Cu- MOF- 74 31 2.1 Introduction Metalorganic frameworks have been used as catalysts for many CN and CO bond forming reactions. .. MINH CITY HO CHI MINH UNIVERSITY OF TECHNOLOGY TRAN BOI CHAU APPLICATION OF Cu- MOF- 74, Cu2 (OBA)2(BPY), MOF- 235 AS CATALYSTS FOR CARBON? ? ?HETEROATOM BOND FORMING REACTIONS Major: Chemical Engineering... properties of Cu- MOF- 74 11 1.3 Carbon? ? ?heteroatom bond forming reactions for the synthesis of benzo-fused heterocycles 14 1.4 Carbon? ? ?heteroatom bond forming reactions for the synthesis of