Rhodium Catalyzed Carbocyclization and Stereoselective Cyclocarbonylation

다국어 초록 (Multilingual Abstract)

The application of transition metals in organic synthesis has led to a number of new synthetic methods that allow for the efficient and elegant construction of complex carbocyclic and heterocyclic systems. The rhodium cluster, Rh4(CO)12 and Rh2Co2(CO)12, serve as excellent catalysts for the silylcarbocyclization (SiCaC) and carbonylative silylcarbocyclization (CO-SiCaC) of enynes. It has been demonstrated that the SiCaC reaction and the CO-SiCaC reaction are effective methods for the construction of synthetically useful substituted cyclopentane, tetrahydrofuran and pyrrolidine systems. The reactions show a broad range of functional group tolerance including esters, amines and alcohols. In addition, bicyclo[4.3.0] ring systems have been constructed by the SiCaC reaction of cyclohexenyl propargylmalonate. This reaction is accompanied by β-hydride elimination rather than reductive elimination process. Conditions to form either the SiCaC or CO-SiCaC product with high selectivity have been optimized. In the CO-SiCaC reaction, a combination of phosphite ligand addition and dilute reaction conditions has significantly improved the selectivity toward the CO-SiCaC product. A possible reaction mechanism has been proposed based on previous mechanistic studies. The rhodium-catalyzed silylcarbocyclization of alkynals and alkynaldimine gave the corresponding cyclized products. The reaction of enynes with a hydroborane or a hydrostannane using a rhodium catalyst failed to give the corresponding carbocyclization product. Rhodium complex-catalyzed arylation-carbocyclization of alkynal with trialkytin gave phenylmethylidene-1-cyclopentanol in good yields.
The carbonylative carbotricyclization of dodec-ll-ene-l,6-diynes (33) and their heteroatom congeners in the presence of a Rh catalyst (1 mol %) and a hydrosilane (0.5 equiv.) under atmospheric pressure of CO gave the corresponding cyclopenta[e]azulenes (34) and their heteroatom congeners in good to excellent yields. Although the silyl group is not included in product, no reaction takes place after 72 h in the absence of a hydrosilane, recovering the starting enediyne. Thus, the hydrosilane proved to be necessary for this reaction to occur. A plausible mechanism for this novel carbonylative carbotricyclization is proposed. The rhodium-catalyzed carbocyclization reaction of diynal 37 was also investigated. The formation of three-ring system failed but two bicyclic compounds were isolated as products.
The desymmetrization of meso-dienes by cyclocarbonylation has been investigated. The reaction of 4-amino-l,6-heptadiene with BIPHEPHOS gave 3'-formylpropyl-2,3,didehydropiperidine in excellent yield. The reaction with chiral ligand, (R,S)-BINAPHOS, also gave the desired cyclized products in good yield but the enantioselective reaction was not achieved. Even if the chiral induction occurs in the first hydroformylation step, the formation of meso-dialdehyde is faster than the cyclocondensation step. There is also a possibility of hemiamidal racemization during this reaction. Thus, new substrates were designed, which contain traps-phenyl substituted alkene groups instead of the terminal alkenes in the previous substrate. In the case of these substrates, the formation of the meso-dialdehydes was blocked and the initial stereoselectivity was kept in the next hydroformylation. Excellent diastereoselectivity as well as enantioselectivity were achieved (>95% ee, >98% de).

목차 (Table of Contents)

• Chapter 1. General introduction = 1
• General concepts of transition metal chemistry = 2
• Chapter 2. Silylcarbocyclization = 7
• I. Introduction = 8
• II. Results & Discussion = 21
• II-l. Optimization of reaction conditions = 21
• II-2. Silanes = 22
• II-3. Synthetic scope of the SiCaC reaction = 23
• II-4. CO-SiCaC reaction & optimization of reaction conditions. = 26
• II-5. Synthetic scope of CO-SiCaC reaction. = 28
• II-6. Reaction mechanism. = 28
• II-7. SiCaC reaction of alkynal = 32
• II-8. Reaction with borane and stannane = 33
• II-9. The proposed mechanism of Hetero-SiCaC reaction = 33
• III. Conclusion = 35
• IV. Experimental = 36
• IV-1. General = 36
• IV-2. Preparation of enynes = 36
• IV-3. General procedure for the catalytic SiCaC reaction = 42
• IV-4. General procedure for the catalytic CO-SiCaC reaction = 51
• IV-5. General procedure for the catalytic Hetero-SiCaC reaction = 55
• IV-6. General procedure for the catalytic Hetero-SiCaC reaction using Sn reagent = 57
• V. References = 59
• Chapter 3. Carbonylative carbotricyclization of enediynes = 62
• I. Introduction = 63
• II. Result and Discussion = 72
• II-1. Discovery of carbonylative carbotricyclization of enediynes = 72
• II-2. Optimization of the reaction conditions = 72
• II-3. Synthetic scope = 74
• II-4. Propoed mechanism = 76
• II-5. 6-7-5 or 5-7-6 ring system = 78
• II-6. Reaction of diynal = 79
• II-7. Synthesis of substrates = 79
• II-8. Reaction of diallens = 82
• III. Conclusion = 83
• IV. Experimental = 84
• IV-1. General = 84
• IV-2. Preparation of Mono-substituted malonates = 84
• IV-3. Preperation of mono-bromides = 87
• IV-4. Preperation of enediynes = 89
• IV-5. General procedure for the catalytic reaction = 99
• IV-6. Preperation of diynal = 104
• IV-7. General procedure for the catalytic reaction of diynal = 105
• V. References = 108
• Chapter 4. Steroselective cyclocarbonylation of dimes = 114
• I. Introduction = 115
• I-1. Hydroformylation = 115
• I-2. Desymmetrization = 122
• II. Result and Discussion = 127
• II-1. Cyclocarbonylation amino alkene and hydroxyl alkene = 127
• II-2. Desymmetrization of meso-diene = 127
• II-3. Preparation of aminodiene = 131
• II-4. Preparation of newly designed aminodienes and catalytic reaction = 132
• III. Conclusion = 136
• IV. Experimental = 137
• IV-1. General = 137
• IV-2. Preparation of 4-amino-1,6-heptadienes = 137
• IV-3. Preparation of 4-amino-1,8-(E)-diphenylhept-1,7-diene = 141
• IV-4. Cyclohydrocarbonylation reaction of 102 = 143
• V. References = 145
• Appendices = 147
• Appendix I. Asymmetric Cabonylative silylcarbocyclization = 147
• Appendix II. Spectra for Chapter 2 = 161
• Appendix III. Spectra for Chapter 3 = 177
• Appendix IV. Spectra for Chapter 4 = 199
• Appendix V. Spectra for Appendix I = 203