TABLE OF CONTENTS
CONTENT PAGE
CHAPTER I : INTRODUCTION AND LITREATURE REVIEW |
1 |
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1.1 Metal-catalyzed cross-coupling reactions |
2 |
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1.1.1 Classification of cross-coupling reactions |
2 |
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1.1.2 Reductive coupling reactions of unactivated organic halides with carbonyl-type compounds |
6 |
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1.1.2.1 Aldehydes as coupling partners in reductive coupling |
6 |
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1.1.2.2 Acid chlorides as coupling partners in reductive coupling |
11 |
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1.1.2.3 Acid anhydrides as coupling partners in reductive coupling |
13 |
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1.2. Traditional methods toward synthesis of alcohols |
14 |
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1.2.1 Grignard addition reactions |
15 |
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1.2.2 Reduction of carbonyl groups |
15 |
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1.3 Synthesis of alcohols using addition of organometals to aldehyde |
16 |
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1.3.1 Addition of organozinc addition to aldehydes |
17 |
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1.3.1.1 Dialkylzinc addition to carbonyl compounds |
17 |
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1.3.1.2 Alkynylzinc addition to aldehydes and ketones |
18 |
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1.3.2 Addition of organoaluminum reagents to aldehydes |
19 |
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1.3.3. Addition of organoborone reagents to aldehydes |
20 |
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1.3.4 Addition of organogalliume reagents to acyl chlorides |
21 |
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1.3.5 Addition of organoindium reagents to aldehyde |
22 |
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1.3.6 Addition of organolithium reagents to aldehydes |
23 |
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1.3.7 Addition of organostannane reagent to aldehyde |
24 |
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1.3.8 Addition of organosilicon reagents to aldehydes |
24 |
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1.4 Ni catalyzed reductive cross-coupling addition reactions |
25 |
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1.5 Objective |
28 |
CHAPTER II : EXPERIMENTAL SECTION |
29 |
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2.1 General |
30 |
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2.2 General procedure for nickel-catalyzed reductive benzylation of aldehydes with Benzyl Halides |
30 |
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2.3 General procedure for nickel-catalyzed reductive benzylation of aldehydes with pseudohalides |
31 |
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2.3.1 Typical procedure for nickel-catalyzed reductive benzylation of aldehydes with benzyl triflates |
31 |
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2.3.2 Typical procedure for nickel-catalyzed reductive benzylation of aldehydes with Benzyl acetates |
31 |
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2.3.3 Typical procedure for nickel-catalyzed reductive benzylation of aldehydes with Benzyl tosylates |
32 |
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2.3.4 Typical procedure for nickel-catalyzed reductive benzylation of aldehydes with Benzyl tritylates |
32 |
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2.3.5 Spectral data |
33 |
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2.4 General procedure for nickel-catalyzed reductivedirect addition of benzyl alcohols to aldehydes usingTCT as C-O bond activating reagent |
44 |
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2.4.1 Spectral data |
45 |
CHAPTER III : RESULTS AND DISCUTON |
52 |
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3.1 Nickel-catalyzed reductive benzylation of aldehydes with benzyl halides and pseudohalides |
53 |
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3.1.1 Introduction |
53 |
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3.1.2 Optimization study |
55 |
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3.1.3 Scope of benzylic substrates |
57 |
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3.1.4 Reaction scope |
59 |
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3.1.5 The proposed reaction mechanism |
67 |
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3.1.6 Conclusion |
69 |
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3.2 Nickel-catalyzed reductive direct addition ofbenzyl alcohols to aldehydes using TCT asC-O bond activating reagent |
70 |
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3.2.1 Introduction |
70 |
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3.2.2 Optimization study |
73 |
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3.2.3 Reaction scope |
75 |
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3.2.4 The proposed reaction mechanism |
79 |
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3.2.5 Conclusion |
81 |
REFRENCES |
82 |
APPENDIX |
91 |
Abstract and Title Page in Persian |
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LIST OF TABLES
TABLE PAGE
Table 3.1. Optimization of the reaction conditions 55
Table 3.2. Direct Ni-catalyzed addition of benzylic
substrates to benzaldehyde 58
Table 3.3. Optimization study 74
LIST OF FIGURES
FIGURE PAGE
Figure 3.1. UV-Spectrum of NiCl2 and NiCl2 in 68
the presence of Zn (0)
Figure 3.2. Activated C-O bond in TBT 72
LIST OF SCHEMES
SCHEME |
PAGE |
Scheme 1.1. Traditional cross-coupling |
2 |
Scheme 1.2. Oxidative cross-coupling reaction |
3 |
Scheme 1.3. Reductive cross-coupling |
4 |
Scheme 1.4. Metal-catalyzed reductive coupling reaction |
5 |
Scheme 1.5. General scheme for the Barbier reaction of allyl electrophile |
6 |
Scheme 1.6. NHK allylation of benzaldehyde using oxazoline ligand |
6 |
Scheme 1.7. NHK allylation of aldehydes catalysed by chromium Complex bis– (8-quinolinolato) (TBOx) chromium catalyst |
7 |
Scheme 1.8. Fürstner’s catalytic system |
8 |
Scheme 1.9. Ni-catalyzed reductive coupling of aryl bromides with benzaldehydes |
9 |
Scheme 1.10. Ni-catalyzed reductive coupling of aryl bromides with benzaldehyde. |
10 |
Scheme 1.11. Ni-catalyzed intramolecular reductive coupling of aryl bromides and chlorides with ketamides |
11 |
Scheme 1.12. Co-catalyzed reductive coupling of aryl bromides with acid chlorides |
11 |
Scheme 1.13. Mechanism for the Co-catalyzed reductive coupling of aryl bromides with acid chlorides via the in situ generation of organozinc species |
12 |
Scheme 1.14. Ni-catalyzed reductive coupling of alkyl halides with acylchlorides |
13 |
Scheme 1.15. Co-catalyzed reductive coupling reaction of aryl bromides with acid anhydrides via the in situ generation of organozinc species. |
13 |
Scheme 1.16. Ni-catalyzed reductive-coupling of unactivated alkyl halides with acid anhydrides |
14 |
Scheme 1.17. Grignard addition to carbonyl compounds and epoxides |
15 |
Scheme 1.18. Reduction of aldehydes and ketones to alcohols |
16 |
Scheme 1.19. Addition of organometallic reagents to aldehydes |
17 |
Scheme 1.20. Dimthylzinc addition to benzaldehyde catalyzed by 1 |
18 |
Scheme 1.21. Alkynylzinc additions to aldehydes |
18 |
Scheme 1.22. Addition of allyl magnesium bromide to organo-aluminium chloride |
19 |
Scheme 1.23. Synthesis of chiral secondary alcohols from benzaldehyde and AlR3 |
19 |
Scheme 1.24. Ni-catalyzed trialkylaluminum additions to aldehydes with sugar-based phosphite ligands |
20 |
Scheme 1.25. Addition of boronate esters to inactivated aldehydes and ketones |
21 |
Scheme 1.26. Addition of organogalliume reagents to acyl chlorides |
22 |
Scheme 1.27. Indium-mediated coupling to α-oxygenated aldehydes |
22 |
Scheme 1.28. Addition of organolithium reagents in the presence of various chiral ligands |
23 |
Scheme 1.29. The reaction of allylstannanes with aldehydes |
24 |
Scheme 1.30. The reaction of phenylmethyldifluorosilane with aldehydes in the presence of a fluoride salt |
25 |
Scheme 1.31. The reductive cross coupling reaction without the intermediacy of an organozinc or organomanganese species |
25 |
Scheme 1.32. Extensive mechanistic studies have suggested that this method combines both polar (arylhalide) and radical chain (alkyl halide) formal oxidative addition mechanisms. |
26 |
Scheme 1.33. First asymmetric acyl reductive cross-couplingwith bisoxazoline ligand |
27 |
Scheme 3.1. Ni-catalyzed addition of benzylic reagents to aldehydes |
54 |
Scheme 3.2 The products of Nickel-catalyzed addition of benzylic substrates to aldehydes |
59 |
Scheme 3.3. Additon of benzylic substra to aldehydes with tert-butyl and a cyano groups |
59 |
Scheme 3.4. Additon of benzylic substrates to aldehydes bearing halogen atoms |
60 |
Scheme 3.5. Additon of benzylic substrate to aldehydes with donating groups |
61 |
Scheme 3.6. Additon of benzylic substrate to aldehydes with unprotected hydroxyl group |
61 |
Scheme 3.7.Additon of benzylic substrate to aldehyde with withdrawing groups |
62 |
Scheme 3.8. Additon of benzylic substrate to aliphatic aldehyde |
62 |
Scheme 3.9. Additon of benzylic substrate to terephthalaldehyde |
62 |
Scheme 3.10. Addition of benzylic substrate to heterocyclic aldehyde |
63 |
Scheme 3.11. Addition of benzylic substrate with an electron donating group to aldehyde |
63 |
Scheme 3.12. Addition of flouriated benzylic substrates to aldehyde |
64 |
Scheme 3.13. Ni-Catalyzed addition of benzylic reagents to aldehydes in the presence of amide and ester groups |
64 |
Scheme 3.14. Competitive experiment between ketones and aldehyde |
65 |
Scheme 3.15. The products of nickel-catalyzed addition of secondary or tertiary benzylic substrates to aldehydes. All yields are isolated yield |
66 |
Scheme 3.16. Reaction of 4-nitrotoluene and aldehyde under optimized condition and in the presence of different bases |
66 |
Scheme 3.17. Ni(0)-catalyzed addition of 4-nitrobenzyl chloride to benzaldehyde |
67 |
Scheme 3.18. Proposed reaction mechanism |
68 |
Scheme 3.19. Some of the reductive cross-coupling addition of organic halides to aldehydes |
71 |
Scheme 3.20. Ni-Catalyzed reductive direct cross-coupling of benzyl alcohols and aldehydes |
72 |
Scheme 3.21. Optimized reaction conditions for Ni-catalyzed addition of benzyl alcohols to aldehydes using TCT reagent |
75 |
Scheme 3.22. Addition of benzyl alcohols with electron-donating groups to aldehydes |
76 |
Scheme 3.23. Additon of benzylic alcohols with electron-withdrawing groups to aldehydes |
76 |
Scheme 3.24. Using heterocyclic substrates from both coupling partner |
77 |
Scheme 3.25. Addition of 4-fluoro benzyl alcohol to 4-chloro benzaldehyde |
77 |
Scheme 3.26. Addition of a sterically hindrance benzylic alcohol to p-cyanobenzaldehyde |
78 |
Scheme 3.27.Addition of secondary and tertiary substrates to aldehyde |
79 |
Scheme 3.28. Proposed mechanism |
80 |
Scheme 3.29. The UV spectra of NiCl2 |
81 |
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