The preparation of bicyclic dienes of the general structures (72), (82), (83) and (162) is described. These materials have been prepared via a novel annulation sequence involving (a) the alkylation of various carbonyl containing substances with the donor acceptor reagents (43), (44), (108)-(114) and (154), (b) the conversion of the alkylation products into the enol triflates, and (c) the palladium(O) catalyzed intramolecular coupling of the enol triflate-vinylstannane moieties via either a "one" or "two pot" process. The Diels-Alder reactions of the "parent" bicyclic diene (75), the cisoid cis diene (145) and the cisoid trans diene (146) are described. Four basic questions regarding the face selectivity, regioselectivity, stereoselectivity and comparative reactivity of the dienes in the formation of the Diels-Alder adducts of general structure (174) are addressed. The annulation sequences described above have been applied to the first total syntheses of the dolastane diterpenoids (±)-(14S)-dolasta-1(15),7,9-trien-14-ol (239) and (±)-amijitrienol (242). Thus, the substituted cycloheptanone (262), prepared in seven steps from the commercially available material (261), was converted via a series of transformations, including the newly developed annulation process, into the bicyclic diene (264). Introduction of the two appendages to (264) proceeded stereoselectively to provide the keto vinylstannane (265). Ring closure was effected with the desired stereochemistry to yield (±)-(239). A reduction, deprotection sequence afforded the ketone (249) from the diene ketal (263). A series of three steps involving an aldol condensation, Swern oxidation and stereoselective methylation provided the diketone (290). Chemo- and stereoselective reduction of (290) followed by protection of the alcohol moiety yielded the silyl ether (303). Cyclization, according to the methodology described herein, and deprotection of the silyl ether moiety produced (±)-(242). [Formula Omitted] / Science, Faculty of / Chemistry, Department of / Graduate

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

No description available.

No description available.

No description available.

by Ivan H.F. Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 63-67). / Acknowledgements --- p.i / Contents --- p.ii / Abstract --- p.iv / Abbreviations --- p.v / Chapter Chapter I --- Introduction / Chapter I-1. --- General background --- p.1 / Chapter I-2. --- Asymmetric Diels-Alder reaction using chiral auxiliaries --- p.2 / Chapter I-2A --- Some well-known chiral auxiliaries --- p.3 / Chapter I-2B --- Carbohydrates as chiral auxiliaries --- p.6 / Chapter I-3. --- Asymmetric Diels-Alder reaction using chiral catalysts --- p.10 / Chapter Chapter II --- Results and Discussion --- p.14 / Chapter II-1. --- "Synthesis of η6-(benzyl 2-O-acryloyl-3,4-O-isopropylidene- β-L-arabinopyranoside) tricarbonylchromium(O) (47)" --- p.15 / Chapter II-2. --- "Syntheses of 4'-methylbenzyl 2-O-acryloyl-3,4-O- isopropylidene-β-L-arabinopyranoside (57) and η6-(4'- methylbenzyl 2-O-acryloyl-3,4-O-isopropylidene-β-L- arabinopyranoside) tricarbonylchromium(O) (56)" --- p.19 / Chapter II-3. --- "Syntheses of naphthylmethyl 2-O-acryloyl-3,4-O- isopropylidene-α-L-arabinopyranosides" --- p.22 / Chapter II-4. --- Diels-Alder reaction using the dienophiles 56 and 57 as the chiral auxiliaries --- p.25 / Chapter II-5. --- "Synthesis of benzyl 3,4-O-methylene-β-L-arabinopyranoside (81)" --- p.32 / Chapter II-6. --- Using the alcohol 81 as the ligand for Lewis acid in the Diels-Alder reaction --- p.36 / Chapter Chapter III --- Conclusions --- p.38 / Chapter Chapter IV --- Experimental Section --- p.40 / Chapter IV-1. --- Experimental section for the asymmetric Diels-Alder reaction using the chiral auxiliaries --- p.41 / Chapter IV-2. --- Experimental section for the asymmetric Diels-Alder reaction using the chiral catalysts --- p.59 / References --- p.63 / List of spectra --- p.68

No description available.

The stereoselective synthesis of urdamycinone B (17) was achieved in a 21% overall yield from C-glycosyl-naphthoquinone 197. The key reaction was the Diels-Alder cycloaddition reaction of 197 and siloxydiene (�)-117 promoted by a chiral Lewis acid derived from (S)-3,3�-diphenyl-1,1�-binaphthalene-2,2�-diol (291), BH₃.THF and acetic acid. An effective kinetic resolution of (�)-117 occurred. Four cycloadducts 199a-d were formed in a ratio between 84:8:2:6 and 70:9:2:19. Aromatisation of the mixture by treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave 200a and 200b in 4:1 ratio. A sequence of reactions involving deacetylation, conversion of a phenyldimethylsilyl group into a hydroxyl group and photooxidation gave a 4:1 mixture of urdamycinone B (17) and its C-3 epimer (154). Separation of these products was achieved by high performance liquid chromatography (HPLC). The C-glycosyl donor, 1,3,4-tri-O-acetyl-2,6-dideoxy-D-glucopyranose (204), was synthesised from readily accessible tri-O-acetyl-D-glucal (237) using two approaches. The first involved a sequence of deacetylation, tosylation, lithium aluminium hydride (LiAlH₄) reduction and acetylation to give di-O-acetyl-6-deoxy-D-glucal (242). The triphenylphosphine hydrogen bromide (TPPHBr) catalysed addition of acetic acid to 242 gave 204 in overall yields ranging from 0 to 32%. The step involving the reduction of the tosylate intermediate was the cause of the variable yields. The alternative synthesis started with the TPPHBr catalysed addition of benzyl alcohol to 237. Subsequent deacetylation, tosylation and reduction with LiAlH₄ gave benzyl 2,6-dideoxy-D-glucopyranoside (250). Acetylation and hydrogenolytic debenzylation gave 3,4-di-O-acetyl-2,6-dideoxy-D-glucopyranose (247). Acetylation gave 204 in 40% overall yield. A third approach to 204 involved selective tosylation of methyl α-D-mannopyranoside (258) and subsequent treatment with 2,2-dimethoxypropane under acidic conditions to give acetonide 255. LiAlH₄ reduction of the tosylate gave methyl 6-deoxy-2,3-O-isopropylidene-α-D-mannopyranoside (256). Acidic hydrolysis of 256 and subsequent acetylation afforded 1,2,3,4-tetra-O-acetyl-6-deoxy-α-D-mannopyranoside (260). Treatment of 260 with hydrogen bromide in acetic acid and subsequent reductive elimination with a zinc-copper couple gave 242. The addition of acetic acid catalysed by TPPHBr afforded 204 in 18% overall yield. The final synthesis of 204 started with thiophenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside (269). A sequence of deacetylation, tosylation and LiAlH₄ reduction gave thiophenyl 2,3-O-isopropylidene-6-deoxy-α-D-mannopyranoside (274). The structure of 274 was confirmed from a single crystal X-ray diffraction study. Hydrolysis of the isopropylidene group of 274 and subsequent acetylation afforded thiophenyl 6-deoxy-2,3,4-tri-O-acetyl-α-D-mannopyrannoside (282). Treatment of 282 with iodine monobromide and subsequent reductive elimination with zinc-copper couple gave 242. The TPPHBr catalysed addition of acetic acid to 242 afforded 204 in 19% overall yield. Differentially protected C-glycosyl donor, 1,3-di-O-acetyl-4-O-benzyl-2,6-dideoxy-D-mannopyranose (265), was synthesised from 274. The benzylation of 274 gave thiophenyl 6-deoxy-2,3-O-isopropylidene-4-O-benzyl-α-D-mannopyranoside (276). Acidic hydrolysis followed by acetylation afforded thiophenyl 6-deoxy-1,2-di-O-acetyl-4-O-benzyl-α-D-mannopyranoside (278) which, upon bromination by iodine monobromide, gave thiophenyl 6-deoxy-1,2-di-O-acetyl-4-O-benzyl-α-D-mannopyranosyl bromide (279). The reductive elimination of 279 with zinc-copper couple gave 3-O-acetyl-4-O-benzyl-6-deoxy-D-glycal (264). The TPPHBr catalysed addition of acetic acid to 264 afforded 1,3-di-O-acetyl-4-O-benzyl-2,6-dideoxy-D-mannopyranose (265) in 16% overall yield from 274. The instabillity of bromide 279 affected the yield of 265. A C-glycosylation study of 2-naphthol 227 and 1,4-dimethoxy-5-hydroxynaphthalene (205) with 2-deoxy-glycosyl acetates was undertaken. Boron trifluoride diethyl etherate (BF₃.Et₂O) and scandium triflate [Sc(OTf)₃] proved effective promoters. For example, the glycosylation reaction of donor 265 and 227, promoted by 0.5 equivalents of Sc(OTf)₃, afforded C-glycoside 2-hydroxy-1-[3�-O-acetyl-4�-O-benzyl-2,6-dideoxy-β-D-manno-hexopyranosyl]-naphthalene (289) in 85% yield.

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / Chemistry / Master / Master of Philosophy