The Development of a Tandem Stille-Oxaelectrocyclization Reaction Citation Zepernick, John F. (2004) The Development of a Tandem Stille-Oxaelectrocyclization Reaction. Master's thesis, California Institute of Technology. doi:10.7907/hc53-h270. https://resolver.caltech.edu/CaltechTHESIS:10022012-135626882 Abstract No abstract. Item Type: Thesis (Master's thesis) Subject Keywords: Chemistry Degree Grantor: California Institute of Technology Division: Chemistry and Chemical Engineering Major Option: Chemistry Thesis Availability: Public (worldwide access) Research Advisor(s): Stoltz, Brian M. Thesis Committee: Unknown, Unknown Defense Date: 6 August 2003 Record Number: CaltechTHESIS:10022012-135626882 Persistent URL: https://resolver.caltech.edu/CaltechTHESIS:10022012-135626882 DOI: 10.7907/hc53-h270 Default Usage Policy: No commercial reproduction, distribution, display or performance rights in this work are provided. ID Code: 7219 Collection: CaltechTHESIS Deposited By: Benjamin Perez Deposited On: 03 Oct 2012 15:15 Last Modified: 08 Nov 2023 00:39 Thesis Files Preview PDF - Final Version See Usage Policy. 4MB Repository Staff Only: item control page

The Development of a Tandem Stille-Oxaelectrocyclization Reaction Thesis by 1ohn F. Zepemick In Partial Fulfillment of the Requirements for the Degree of Master of Science California Institute ofTechnology Pasadena, California 2004 (August 6, 2003) John F. Zepemick Advisor: Brian M. Stoltz Research Summary: The Development of a Tandem Stille-Oxaelectrocyclization Reaction Introduction Metal-mediated coupling reactions are an essential tool for the synthetic chemist, and are among the most important methods for forming carbon-carbon bonds. Tandem reactions are also useful since they can rapidly and efficiently build up complex structures. With these key features in mind, a palladium-catalyzed tandem Stille-oxaelectrocyclization has been developed in our labs based upon work toward the total synthesis of saudin (1). Saudin, a labdane diterpenoid, was isolated from the leaves of Cutia 0 richardiana, a toxic plant indigenous to Saudi Arabia 1. Saudin is interesting both for its unique structural features and its potent bioactivity. Saudin possesses seven stereogenic centers, including two quaternary carbons and its caged, Saudin (1) highly oxygenated, polycyclic framework presents a formidable synthetic challenge. Saudin is a potent hypoglycemic agent and therefore could be a promising lead structure for discovering therapeutics for the treatment of diabetes'. Since the isolation of saudin in 1985, the molecule has been the subject of considerable synthetic effort. These efforts have resulted in elegant syntheses of (±)-saudin by Winkler2 and (-)-saudin by Boeckman3. Research by my colleagues in the Stoltz group has explored an alternative strategy for the enantioselective synthesis of saudin (Scheme 1t Scheme 1 : Retrosynthetic Analysis of Saudin 0 0 ::::::> ::::::> 0 3 Saudin (1) 0 TBJ ~:Sn8u 3 + ~ I o 0 ·~ JJ Stille Coupling 0 6n-oxaelectrocy c lization 0 ¢:= 0 14a Sa 4 The key disconnection in this sequence is the opening of the 2H-pyran 3 via a retrooxaelectrocyclizatjon to reveal oxatriene 4 , followed by disconnection across the C(5)-C( 16) bond via a Stille coupling. This reveals the relatively simple coupling partners Sa and 14a which are each accessible in three steps from readily available starting materials. When stannane 14a and iodoenone Sa were subjected to Cu(l)-accelerated Stille coupling conditions, it was found that the desired coupling reaction occurred. However, product 4 was not observed. Instead, the substrates reacted further, undergoing an oxaelectrocyclization to yield furan appended tricycle 3 (Scheme 2). This tandem reaction, which rapidly builds up the core of saudin, was selected for further investigation to evaluate its utility as a more general synthetic methodology. Scheme 2 ~ SnBu I~ Pd(PPh3)4 j TB SOJ : P 0 3 ~ 0 1 o Cui + ··., DMF, 23•-c '' (92% yield) 0 0 14a Sa (Not Observed) From Total Synthesis to Synthetic Methodology The tandem Stille-oxaelectrocyclization has several interesting features. It is highly diastereoselective, convergent, and requires mild reaction conditions with low catalyst loading. These mild conditions are particularly noteworthy given the rather sterically hindered nature of the coupling partners. The reaction is also of interest since oxaelectrocyclizations are currently a relatively under-utilized transformation in organic synthesis. Recently, there have been notable, although isolated, examples used in the syntheses of Torreyanic Acid by Porco5 , Arisugacin A by Hsung 6 , and Sterekunthal A by Trauner7• In pursuing this reaction as part of a general synthetic method for the formation of 2Hpyrans, the key issues examined were the substrate scope of the reaction, the factors affecting the efficiency of the Stille coupling, and the variables that affect the equilibrium between the 2Hpyran and the 1-oxatriene. Synthesis of Stannane and Iodoenone Substrates Sever al different routes were utilized to obtain the Scheme 3 TBO~~ 2 ) )lH stann ane coupling partners. The initial method involved addition of a Grignard reagent into an 1) E1MgBc, THF TBOP? 7 R=3-furyl, Sa R=Ph, Bb R=t-Bu, Be Reage:~DPS(O~ Jones Acetone J-OH 9a, 9b,9c aldehyde followed by a Jones oxidation (Scheme 3). Alternatively, the alky nones could be formed directly via a Sonagashira coupling between a terminal acetylene and an acid chloride8 (Scheme 4). Scheme 4 Pd(PPh3)2CI2 Cu~NEt3 0 R)lCI + 0 ~ ~OTBDPS (58-80% yield) A'-- \_ OTBDPS R=Ph, 11b R=t-Bu, 11c 7 0 1Db, 10c = + Ph Ph.Jl.CI 0 Pd(PPh3hCI2 Cui, NEt3 Ph PJ (80% yield) 11b 12 13 Next, these alkynones were converted to (Z)-vinyl stannanes. This transformation was accomplished by first treating hexabutylditin with n-butyl lithium, followed by the addition of copper thiophene!. This generated (Bu 3Sn)CuSPhLi in situ, which was then reacted with an alkynone, to give exclusively the desired olefin geometry9 (Scheme 5). Scheme 5: Synthesis of (Z)-Stannanes 1) n-Bull, THF, 0°C 2) CuSPh, 0°C 3) R=3-fury/, 10a R=Ph, 10b R:::t-Bu, 10c 0 Sn8u3 O~OTBQpS R~OTBOPS U~1~~ R -78"C -> -40°C (27-30% yield) 1) n-Bull, THF, 0°C 2) CuSPh, 0°C 0 SnBu3 Bu3Sn-SnBu 3 - - - - - - - - - - . II ~I 3) 0 Ph~Ph ' Ph = 13 Ph 15 -78°C -> -40°C (40% yield) In order to examine the scope of the reaction, several iodoenones were synthesized from readily available enones 10 (Scheme 6). These iodoenones feature varying ring sizes, differing amounts of steric bu lk around the ring, and 18 features a lactone. From work toward the synthesis of saudin, it was known that the bicyclic enone Sa and the acyclic iodoenone 24 were also useful substrates for the tandem Stille-oxaelectrocyclization reaction. Scheme 6: lodoenones 0 j) ·-o 0 12, pyridine, CH 2 CI 2 12 , pyridine, CCI, (54% yield) (85% yield) 16 17 n + 33 18 0 0 ~ IBX, DMSO 1o•c (53"/o yield) 19 0 + 12> pyridine, CCI, I n {85% ,,••, 20 21 ·'6·~0' 22 23 24 The bicyclic stannane 25 was synthesized from bicyclic brornoenone Sb through a cross coupling with hexabutylditin (Scheme 7). In examining this reaction, it was found that using the iodoenone gave primarily non-specific decomposition and only a trace amount of the desired product. The pUlity of bromoenone Sb was a critical factor in the success of the reaction , with slightly impure material leading to significant erosions in yield. Scheme 7 0 0 X& 3 Pd(Ph-Sn 3) 4_,SToluene --B-u _n-B u_3_ _ _ 140"C, 48 h Bu3sn~l (X=I, trace yield) (X:Br, 58% yield) 0 X=l, Sa X=Br, 5b 0 25 Exploring the Tandem Stille-oxaelectrocyclization Reaction With a variety of stannanes and iodoenones in hand, the substrate scope of the reaction was investigated. Work toward the synthesis of saudin resulted in the syntheses of several different furan appended tricycles (Figure 1). From these studies, it was shown that sub strates with varying alkyl substituents in the 4-position of the 2H-pyran successfully underwent the sti lle-oxaelectrocyclization. Figure 1 0 26 27 3 As a starting point, the coupling between iodoenone 17 and stannane 14a was attempted to explore the substrate scope for the iodoenone (Scheme 8). These substrates successfully underwent the Stille coupling. However, upon examination of the 13 C spectrum, it was clear that two carbonyl peaks were present, indicating that the oxaelectrocyclization did not occur. Scheme 8 0 TB7DSO ~ 0 "" I~~ Pd(PPh 3)4 , Cui __ DM_F_, ~ (50"/o yield) 0 Sn8u3 + _23_"C---I~ 0 _..., 14a 28 17 29 (Observed Product) Since iodoenone 17 was not a useful substrate for the oxaelectrocyclization, the bicyclic iodoenone Sa served as a better test substrate to examine various substituents in the 6-position of the resulting 2H-pyran. Stannane 14c successfully underwent both the Stille coupling and the oxaelectrocyclization in tandem when coupled to iodoenone Sa. However, a new problem emerged- the reaction conditions that Scheme 9 TBDP~SO/'--...., 0 produced furan appended tricycles in good yield produced Pd(PPh3)4 _ _c_u...;...l ,_ DM _ F_ _ _ tert-butyl 23•c I -. ; : ;: o ··..,, (20-40"/o yield) 0 appended tricycles in 1ow and variable 14c yields (Scheme 9). 5a 30 0 In an effort to alleviate this problem, a number of reaction parameters were screened to further optimize the reaction (Table 1). A variety of ligands and palladium sources did little to improve the reaction. Table 1: Optimization Studies Pd Source, ligand, additive 14c + Sa 30 solvent• Solvent Additive Other lodoenone consumed ? Stannane consumed? Yield Pd(PPh:J) 4 DMF Cui Argon no yes 43%c 2 Pd(PPh:J4 DMF Cui 50 ° C no yes trace 3 Pd 2(dbab PPh3 (1 0 mol%) DMF Cui no yes 11 %b 4 Pd2(dbah PPh3 DMF Cui no yes 45%b 5 Pd 2(dbab AsPh3 DMF Cui no yes trace 6 Pd 2(dbah o-tolyl DMF Cui no yes trace 7 Pd(PPh:J 4 DMSO CuCI, LiCI no yes 0%" 8 Pd(DPPF)CI 2 DMF Cui no yes oo;.d 9 Pd(PPh3hCI2 DMF Cut no yes 0% Entry Ligand Pd Source S0 ° C • S mol% Pd, 20 mol% ligand, 0.1 M in Sa, 1 equiv Cui. 1 equiv. Sa, 1.2 equov 14c 0 Yield measured by NMR with 1,3,5-tnmethoxybenzene as an internal standard. c Isolated yield. d DPPF=1,2·bis(diphenylphosphino)ferrocene. 8 10 mol% Pd, 5 equrv CuCI. 6 equiv UCl. A pattern did emerge that illustrated the key problem facing the reaction. Although the stannane was present in slight excess, it was always consumed before the iodoenone. This decomposition of the stannane led to low yields of the desired Scheme 10: Proposed Catalytic Cycle product and the recovery of unreacted iodoenone. Previous studies in our lab have demonstrated that copper(!) iodide was necessary for this Stille coupling to proceed. This copper effect in Stille couplings has been well studied 11. 12 , and two distinct mechanisms have been proposed depending upon the reaction medium. 13' 14 In the case of very polar solvents such as DMF or NMP, copper(!) salts are believed to undergo Cu/Sn transmetallation, resulting in the formation of an organocopper species (Scheme 10). In the case of less polar solvents such as THF, the copper(!) is believed to act as a ligand scavenger of free phosphine, thus accelerating the Sn/Pd transmetallation. In an attempt to further optimize the reaction, the amount of copper iodide was varied. When using substoichiometric amounts, the reaction became very sluggish and even lower yields were observed. However, these experiments did lead to a useful observation. When catalytic amounts of copper iodide were used, the stannane did not decompose (Table 2, entries 2 and 3). In a control experiment, iodoenone Sa was excluded from the reaction. Decomposition was observed in the presence of copper iodide (Table 2, Entry 4), while no reaction was seen in the absence of copper iodide (table 2, entry 5). From these results, it was hypothesized that copper(!) was undergoing oxidation to a copper(II) species, which is known to facilitate the homocoupling of stannanes 15• In order to test this hypothesis, the reaction was run in an inert atmosphere glovebox, thus rigorously excluding oxygen. To our delight, the desired product was obtained in high yield (table 2, entry 6). Table 2: Examining the Role of Copper Iodide Pd Source, ligand, Cui 14c + 30 Sa Stannane consumed? Yield 100% yes 4S%b S% no trace Pd(PPh3)4 0% no no reaction 4 Pd(PPh3) 4 100"/o no iodoenone Sa yes decomposition s Pd(PPh3)4 0% no iodoenone Sa no no reaction Entry Pd Source Ligand Cul (mol"'o) Pd2(dbab PPh3 2 Pd2(dbab PPh3 3 Other 6 Pd(PPh3)4 100"/o in glovebox no • 5 mol% Pd, 20 mol% ligand. 0.1 M in Sa, 1 equiv Sa, 1.2 equiv 14c. b Isolated yield. Having found that rigorously anaerobic conditions were optimal for this reaction, a variety of other substrates were examined. It was discovered that subtle changes in molecular structure had a large impact on the effectiveness of the oxaelectrocyclization. For some substrates the Stille coupling was successful, but the product would exist primarily as the 1,3 ,5oxatriene (Scheme 11). In other cases, the Stille coupling was Scheme 11 0 successful, and the oxaelectrocyclization yielded an equilibrium mixture of products )6 + 14a Pd(PPhJ)4 Cui, DM F 23"C (50% yield) 17 (Table 3). These equilibrium mixtures were 0 difficult to characterize because the species in solution were rapidly interconverting on the ·~ NMR timescale, causing the peaks in the NMR + 14a Pd(PPhJ)4 Cui, DMF 23"C {62"k yield) 32 21 spectrum to be very broad. To alleviate this problem, the 1H NMR spectra were taken at -30 °C. These products were obtained in useful yields and often in a good ratio of cyclized to uncyclized product. Table 3 Cyclized Product Uncycllzed Produtc Ratio { Cyclized :Uncyclized)" 7:1 90% 10 : 1 66% 10 : 1 73% 1 :3 62"/o ~, 0 mo~ rl 0 34a 34b ffiDPSO~ ffiDPSO~ r I--=::: Ph 0 35a Ph I 0 35b • Ratio determined by 1 H NMR spectroscopy. 0 Isolated y1eld. When varying the substitution at the 4-position of the resulting pyran ring, it was found that a phenyl ring was not well tolerated in the reaction. These reactions yielded complex mixtures of products (Scheme 13). The most successful substrates were Scheme 12 those incorporating iodoenones Sa or 18 with a 0 stannane that had alkyl substitution in the 4- + position of the resulting pyran ring, while both ·~ ........ , .. 0 5a complex mixture alkyl and aromatic substitution worked well in 0 the 2-position. These products could be obtained + '& 0 exclu sive formation of the desired 2H-pyran 5a 37 product (Table 4). Table 4 Yield" Yield" 65% 92% TBDPM I~ 0 94% rnoP:M I~ ...,,, o 67% 0 0~0 I 41 30 TBDPSO 0 94% ffiDPSO~ I~ Ph Ph 0 42 • Isolated Yield o 92% ... ... ...-tr Theoretical Calculations One of the key difficulties in developing oxaelectrocyclizations as a useful synthetic tool is a typically small (or even unfavorable) thermodynamic driving force for the reaction. This often leads to the formation uncyclized products or equilibrium mixtures of products. Rather than relying solely on trial and Table 5: Enthalpy of Reaction for Oxaelectrocyclizations Entry 1, 3,5-oxatriene 2H-pyran AH (kcaVmol) 2 error, we turned to theoretical 2.046 calculations to examine substrates for the tandem Stille0.083 oxaelectrocyclization reaction. 2 Using Spartan '02 for Macintosh, AM 1 calculations were used to evaluate the enthalpy -3.71 3 of reaction for the conversion of -3.84 1,3,5-oxatriene to 2H-pyran. In 4 order to simplify the calculations, methyl groups were used to s -1.62 approximate longer alkyl groups • AMl resun based on lowest energy conformation of 1.3,5-hexatriene and 2H-pyran. in the 4-position of the pyran ring. The results agreed well with the observed experimental observation. In the cases where the calculated enthalpy was endothermic, the 2H-pyran product was not observed experimentally (Table 5, entries 1, 2). In the cases where the calculated enthalpy was exothermic, the 2H-pyrans were obtained as the major products from the tandem stille-oxaelectrocyclization process (Table 5, entries 3,4,5). While these methods are not as precise as higher level calculations 16 , they clearly offer some degree of predictive power for evaluating potential oxaelectrocyclization substrates. Conclusions While the tandem Stille-oxaelectrocyclization reaction is not yet a general method for the synthesis of 2H-pyrans, many interesting subtleties of the reaction have been explored. The key problem with this process is that unfavorable thermodynamics limit the substrate scope of the oxaelectrocyclization. Nonetheless, several highly substituted 2H-pyrans were synthesized using this reaction. This work demonstrates the utility of tandem reactions for the construction of complex molecular architectures, and also shows the potential, and inherent difficulties, of using oxaelectrocyclizations as a synthetic tool. Experimental Section Material and Methods. Unless stated otherwise, reactions were performed in flame-dried glassware under a nitrogen atmosphere, using deoxygenated solvents dried over activated alumina. All other commercially available reagents were used as received. Thin-layer chromatography (TLC) was performed using E. Merck silica gel 60 F254 precoated plates (0.25 mm). Silica gel (particle size 0.032-0.063 mm) was used for flash chromatography. 1H and 13C NMR chemical shifts are reported relative to Me4 Si (6 0.0). Mass spectra were performed at the California Institute of Technology mass spectrometry facilities. General Procedure for the Preparation of Propargyl Alcohols. A terminal alkyne (18 mmol, 1 equiv) was added to a stirred solution of ethyl magnesium bromide (18 mmol, 1 equiv) in diethyl ether ( 10 mL) at 23 oc. This reaction mixture was stirred for 30 minutes. Aldehyde (21 mmol, 1.2 equiv) was added dropwise and the reaction mixture was stirred until the reaction reached completion as determined by TLC. After quenching with 1 M HCl, the organic layer was washed three times with water and once with brine. The organic layer was separated and dried over MgS04 • Following concentration in vacuo, a portion of the resulting crude mixture was carried on to the oxidation step. General Procedure for the Preparation of Ynones by Jones Oxidation. The crude alcohol (7 .2 mmol, 1 equiv) was dissolved in acetone (15 mL). This solution was cooled to 0 oc and Jones reagent (15 mmol, 2.1 equiv) was added slowly to the stirred reaction mixture. After stirring 30 minutes, the excess Jones reagent was quenched with isopropanol. The reaction mixture was extracted three times with ether, washed once with aqueous NaHC03 , and once with brine. After drying over MgS04 and concentrating in vacuo, the crude ynone was purified by flash column chromatography on silica gel. General Procedure for the Preparation of Ynones via the Sonagashir a Reaction. A Schlenk tube was charged with Cui (0.2mmol, 2 mol%), Pd(PPh3) 2Cl 2 (0.06 mmol, 0.5 mol%), and terminal alkyne (10.8 mmol, 1 equiv). Next, triethylamine (22 mL) was added to the Schlenk tube and the mixture was degassed by the freeze-pump-thaw method. Then, an acid chloride (14.2 mmol, 1.3 equiv) was added dropwise to the stirred reaction mixture at 23 oc. The reaction mixture was stirred 12 hours. Once the reaction was complete, water was added to the reaction mixture and the organic material extracted three times with pentane. The organic layer was then washed thrice with water and once with brine and then dried over MgS04 • After concentrating in vacuo, the crude ynone was purified by flash column chromatography on silica gel. General Procedure for the Preparation of (Z)-Vinyl Stannanes. n-B utyllithiurn (4.5 rnmol, 1.2 equiv) was added to a stirred solution of bis(tributyltin) (4.5 rnrnol, 1.2 equiv) in THF (40 rnL) at 0 °C. After stirring 30 minutes, CuSPh (4.5 rnrnol, 1.2 equiv) was added. After an additional 30 minutes of stirring, the reaction mixture was cooled to -78 oc. Alkynone (3.8 mrnol, 1 equiv) was added slowly to the reaction mixture and stirred for 30 minutes at -78 °C. The reaction was then warmed to -40 oc and stirred for an hour and then allowed to warm to room temperature. Aqueous ammonium chloride was added to quench the reaction, and the organic material was extracted with ether. After separating the organic layer, methanol was added, forming a yellow slurry that was filtered through celite. The filtrate was concentrated in vacuo to provide the crude (Z)-vinyl stannane, which was then purified by flash column chromatography on silica gel. General Procedure for Tandem Stille-oxaelectrocyclization Reactions. Pd(PPh3) 4 (3 .3x IO..o moles, 5 mol %), Cui (5.7xl0·5 moles, 1 equiv) and iodoenone (5.7xl0-5 moles, 1 equiv) were weighed into a oven-dried vial. The stannane (6.8x10·5 moles, 1.2 equiv) was concentrated in vac uo from benzene in a separate flask. These materials were then taken into the glovebox. Next, the stannane was dissolved in DMF (0.7 mL) and the resulting solution was transferred into the vial containing the other reagents. The reaction was stirred for 24 hours. Then, water was added and the reaction mixture extracted with ether. The organic layer was dried by passing it over a short silica plug. The material was concentrated in vacuo to yield the crude product, which could then be purified by flash column chromatography on silica gel. Sometimes after flashing a compound, some alkyl tin contaminants remained. These were removed by dissolving the material in acetonitrile and washing three times with hexane. Concentrating the acetonitrile layer in vacuo produced the desired product free of alkyl tin byproducts. Furan Appended Tricycle 3. Prepared using the general procedure for the tandem Stilleoxaelectrocyclization reaction using Sa (43.5 mg, 0.15 mmol) and 14a (130.7 mg, .0.18 mmol). Purified by flash chromatography on silica gel (10:1 hexanes:EtOAc -7 7:1 hexanes:EtOAc). 80-92% yield, yellow foam/oil; 1H NMR (300 MHz, CDC13) o7.714 (s, UI), 7.656-7.612 (comp. m , 4H), 7.448-7.3 17 (comp. m, 7H), 6.4565 (d, J=2.1 Hz, lH), 5.817 (s, 1H), 4.7435 (d, J=11.1 Hz, 1H), 3.967-3.880 (comp. m, 3H), 3.095 (dt, J=2.4, 6Hz, 2H), 2.68-2.2 .368 (comp. m, 2H), 2.044-1.996 (comp. m, 2H), 1.542 (s, 3H), 1.071 (s 9); 13C NMR (75 MHz, CDC1 3) o 194.666, 179.206, 151.477, 144.311, 143.059, 135.579, 133.654, 133.595, 129.722, 172.707, 120.713, 113.925, 107.301, 105.496, 86.5143,71.5361, 63.3087, 44.9139, 36.6156, 34.9895, 27.8237, 26.8780, 19.2637 , 14.8827; IR (film) 2932.0, 2857.7, 1785.0, 1659.4, 1112.1 cm·1; HRMS (FAB+) m/z calc'd for [C34H370 6Sit: 569.2359, found 569.2346. Bicyclic lodoenone Sa. Used as received from Taichi Kano. H NMR (300 MHz, CDC13) o 1 4.97 (d, J=15 Hz, 1H), 4.83 (d, J=15 Hz, lH) , 2.86-2.8 1 (comp. m, 2H), 2.31-2.13 (comp. m, 2H) , 1.56 (s, 3H); 13 C NMR (75 MHz, CDC13) o 189.20, 176.80, 166.48, 99. 13, 73.16, 45.96, 31.97, 29.48, 21.59: HRMS (FAB+) mlz calc'd for [C9H 100 3It: 292.9675, found 292.9685 . Ynone lOb. Prepared using the general procedure for the preparation of ynones VIa a Sonagashira coupling with llb (1.65 mL, 14.0 mmol) and 7 (3.3g, 10.8 mmol). Purified by flash chromatography on silica gel (8: 1 hexanes:EtOAc eluent). 27%, clear, brownish oil; 1 H NMR (300 MHz, CDC13 ) b 8.174-8. 143 (camp. m, 2H), 7.725-7.686 (comp. m, 4H), 7.583 (tt, 1=9.6, 1.5 Hz, 1H), 7.467-7.354 (camp. m, 8H), 3.918 (t, 1=6.6 Hz, 2H), 2.748 (t, 1=6.6 Hz, 2H), 1.12 (s, 9H); 13 C NMR (75 MHz, CDC13 ) o 178.138, 136.814, 135.584, 133.969, 133.240, 129.876, 129.685, 128.515, 127.831, 93.796, 80.369, 61.510, 26.802, 23.482, 19.232; IR (film) 2931.3, 2857.7, 2237.9, 2207.1, 1645.4, 1645.4, 1263.9, 1112.6 cm· 1; HRMS (FAB+) m/z calc'd for [C27H 270 2SW: 411.1780, found 411.1792. Ynone lOc. Prepared using the general procedure for the preparation of ynones via a Sonagashira coupling with llc (1.8 mL,14.2 mmol) and 7 (3.36g, 10.8 mmo1). Purified by flash chromatography on silica gel ( I: 1 hexanes:DCM eluent). 58%, clear, brownish oil; 1 H NMR (300 MHz, CDC13) b 7.700-7.662 (comp. m, 4H), 7.470-7.364 (comp. m, 6H), 3.828 (t , 1=6.6 Hz, 2H), 2.632 (t, 1=6.6 Hz, 2H), 1.197 (s, 9H), 1.051 (s, 9H); 13C NMR (75 MHz, CDC1 3) b 194.345, 135.563, 133.265, 129.839, 127.796,92.624, 79.536, 61.523, 44.639, 26.760, 26.068, 23.260, 19.188; IR (film) 2932.2, 2858.7, 2210.5, 1809.8, 1670.4 cm· 1; HRMS (FAB+) m/z calc'd for [C25H31 0 2Sit: 391.2093, found 391.2098. Stannane 14b. Prepared using the general procedure for the preparation of (Z)-vinyl stannane from ynone lOb (1.1 g, 2.5 mmol). Purified by flash chromatography on silica gel (10:1 hexanes:EtOAc -7 6:1 hexanes:EtOAc) . 31% yield, clear, light brown oil; 1H 1\TMR. (300 MHz, CDC13) () 7.977-7.947 (camp. m, 2H), 7.702-7.670 (comp . m, 4H), 7.634 (s , 1H), 7.551 (camp. m, 1H), 7.481-7.353 (comp. m, 8H), 3.794 (t, 1=6.6 Hz, 2H), 2.830 (t, 1=6.6, 1snH=42 Hz, 2H), 1.479-1 .416 (comp. m, 6H), 1.271 (m, 1=7.2 Hz, 6H), 1.058 (s, 9H), 0.985-0.931 (comp. m, 6H), 0.848 (t, 7.5H); 13 C NMR (75 MHz, CDC13) c 189.487, 175.368, 138.328, 135.614, 134.100, 133.812, 132.575, 129.670, 128.519, 128.496, 127.696,62.856, 43.504, 29.321, 27.493, 26.884, 19.273, 13.752, 11. 151; IR (film) 1651.2 cm· 1; HRMS (FAB+) m/z calc'd for [C39H550 2SnSit: m/e 703.2993, found 703.3007. Stannane 14c. Prepared using the general procedure for the preparation of (Z)-vinyl stannane using ynone lOc (2.3 g, 5.8 mmol). Purified by flash chromatography on silica gel (50: I hexanes:EtOAc). 28% yield, clear, light brown oil; H NMR (300 MHz, CDC1 3) o 7.715-7.683 1 (comp. m, 4H), 7.455-7.3477 (comp. m, 6H), 7.105 (s, 1H), 3.7003 (t, 1=6.65 Hz, 2H), 2.692 (t, 1=6.65, 1snH=43.56 Hz, 2H), 1.4385-1.33658 (comp. m, 6H), 1.240 (m, 1=7.7 Hz, 7H), 1.1337 (s, 9H), 1.04245 (s, 9H), 0.894-0.813 (comp m., 14H): 13C NMR (75 MHz, CDC13) o 204.562, 171.438, 135.601, 133.812, 133.564, 129.645, 127.665, 62.882, 43.239, 42.518, 29.278, 27.477, 26.859, 26.427, 19.239, 13.748, 11.016; IR (film) 2956.1, 2857.3, 1671.1,1113.1 em·•; HRMS (EI+) m/z calc'd for [C33 H5 .0 2SiSnt: 627.2680, found 627.2666. Iodopyranone 18. Compound 33 (0. 1 mL, 1.16 mmol) was dissolved in CC14 (1 ml) and pyridine (1 ml). Then, a solution of iodine (0.9 g, 3.4 mmol), in 1:1 pyridine/CC1 4 (6 mL) was slowly added at 0 oc. The reaction was quenched with aqueous sodium thiosulfate and the organic material was extracted using CH2Cl2 • The organic layer was then washed once with brine and dried over MgS0 4 • Following concentration in vacuo, the crude product was purified 1 by flash chromatography on silica gel (1 0:1 hexanes:EtOAc). 85% yield, yellowish solid. H NMR (300 MHz, CDC1 3) o 7.595 (t, 1=4.65 Hz, 1H), 4.484 (t, 1=6 Hz, 2H), 2.515 (dt, 1=4.65, 6 Hz, 2H); 13 C NMR (75 MHz, CDC1 3) o 159.654, 154.392, 89.487, 67.044, 28.238; IR (NaCl, CC14) 1723.7 cm- 1; HRMS (FAB+) mlz calc'd for [C5H60 2 It: 224.9413, found 224.9405. Iodocyclohexenone 22. Used as received from David Ebner. 1 H NMR (300 MHz, CDC1 3) o 7.790 (t, 1=4.5 Hz, 1H), 2.704-2_659 (camp. m, 2H), 2.466 (dt, 1=4.5, 6Hz, 2H), 2.149-2.064 (camp m, 2H); 13C NMR (75 MHz, CDC13) o 192.233, 159.518, 103.874, 37.275, 29.964, 22.871; HRMS (FAB +) m/z calc'd for [C6 H80It: 222.9620, found 222.9622. Iodocyclopentenone 23. Us~d as received from David Ebner. H NMR (300 MHz, CDC13) o 1 8.003 (dt, 1=0.9, 3 Hz, 1H), 2.782-2.739 (camp. m, 2H), 2.495-2.464 (camp_ m, 2H); 13C 1\TMR (75 MHz, CDC13) o 204.080, 169.694, 102.879, 31.299, 30.966. Bicyclic Stannane 25. Bromoenone Sb (4g, 16.3 mmol), bis(tributyltin) (16.5 ml, 32.6 mmol), and Pd(PPh 3) 4 (280 mg, 1.5 mol %) were added to toluene (2 10 mL) under an atmosphere of argon. The reaction mixture was stirred at reflux for 48 h. Following filtration through celite and concentration in vacuo, the crude product was purified by flash column chromatography (1 0: I hexanes:EtOAc -7 7:1 hexanes:EtOAc). 58% yield, brownish-orange oil. 1H NMR (300 MHz, CDCl 3) o 5.028 (d, 1=14.65 Hz, 1H), 4.790 (d, 1=14.65 Hz, 1H), 2.666-2.468 (camp. m, 2H), 2.2318 (ddd, 1=13.3 , 5.3, 2.1 Hz, 1H), 2.040 (td, 1=13.3, 6.6 Hz, 1H), 1.663-1.581 (comp. m, 3H), 1.483 (s, 3H), 1.471 -L240 (camp. m, 13H), 1.029-0.861 (camp. m, 14H); 13C 1\TMR (75 MHz, CDC13) o 178.361, 169.627, 139.507 , 69.887, 42.200, 32.142, 29.199, 28.292, 27.244, 26.800, 21.580, 17.307 , 13.655, 10.964; IR (film) 1783.6, 1654.0 cm-1; HRMS (FAB+) m/z calc'd for [C21 H35 0 3Snt:455.1608, found 455.1603. tert-Butyl Appended Tricycle 30. Prepared using the general procedure for the tandem Stilleoxaelectrocyclization reaction using 14c (43 mg, .063 mmol) and Sa (15.3 mg, 0.0525 mmol). Purified by flash chromatography on silica gel (hexanes -7 5:1 Hexanes/EtOAc). 94% yield, yellow oil. 1H NMR (300 MHz, CDC1 3) 6 7.658-7.620 (comp. m, 4H), 7.46-7.33 (comp. m, 6H), 5.4527 (s, IH), 4.6363 (d, 1=10.8 Hz, lH), 3.971-3.828 (comp. m, 3H), 3.11 (app. dt, 1= 12, 5Hz, 1H), 2.83745-2.75063 (comp. m, 1H), 2.620-2.460 (m, 1=9 Hz, 1H), 2.38 (app. dt, 1H), 1.95 (app. q, 1=5 Hz, 2H), 1.4696 (s, 3H), 1.10635 (s, 9H), 1.04435 (s, 9H); 13C NMR (75 MHz, CDC13) 6 194.790, 179.381, 168.713, 151.825, 135.568, 133.675, 129.707, 127.681, 112.935, 103.354, 85.983, 71.353, 63.514, 44.869, 36.735, 35.692, 34.986, 27.801, 27.185, 26.882, 19.286, 14.677; IR (film) 2932.3, 2858.1, 1787.3, 1663.2 cm·1; HRMS (FAB+) m/z calc'd for [C34 H43 0 5Sit: 559.2880, found 559.2878. Phenyl Appended T r icycle 39. Prepared by the general procedure for the tandem Stilleoxaelectrocyclization reaction using Sa (16.6 mg, 0.057 mrnol) and 14b (48 mg, 0.068 mmol). Purified by flash chromatography on silica gel (hexanes -7 5:1 Hexanes/EtOAc eluent). 94% yield, yellow oil 1H NMR (500 MHz, CDC13) 6 7.620 (m, 5H), 7.3875 (m, 10H), 6.149 (s, 1H), 4.759 (d, 1= 11 Hz, 1H), 3.950 (m, 3H), 3.103 (t, 1=6 Hz, 2H), 2.579 (m, 1H), 2.443 (dt, 1=7.4, 13.5 Hz, 1H), 2.051 (m, 2H), 1.566 (s, 3H), 1.031 (s, 9H); 13C NMR (125 MHz, CDC1 3) 6 194.855 , 179.327, 156.397, 151.482, 135.580, 133.670, 132.074, 131.001, 129.708, 128.769, 127.700, 126.089, 114.161, 105.541, 86.686, 71.479, 63.330, 45 .006, 36.652, 35.029, 27.830, 26.884, 19.273 , 14.945; IR (thin film) 2931.9, 2857.4, 1785.6, 1661.5 crn·1; HRMS (FAB+) m/z calc'd for [C36H 390 5 Sit: 579.2567, found 579.2565. Furan Appended Bicycle 40. Prepared using the general procedure for the tandem Stilleoxaelectrocyclization reaction using 14a (53 mg, 0.076 rnrnol) and 33 (14 mg, 0.063 rnmol). Purified by flash chromatography on silica gel (hexanes -7 10:1 hexanes:EtOAc). 65% yield, yellow oil. H :NMR (500 MHz, CDC13) o 7.732 (s, 1H), 7.645 (app. d, 1=6.5 Hz, 4H), 7.414- 1 7.262 (comp. rn, 7H), 6.488 (s, lH), 5.912 (s, 1H), 4.667 (t, 1=5 Hz, 1H), 4.365-4.217 (cornp. m, 2H), 3.925 (t, 1=6 Hz, 2H), 3.111-3.011 (comp. m, 2H), 2.329 (app. q, 1=5 Hz, 2H), 1.03387 (s, 9H) ; 13C NMR (125 MHz, CDC13) o 164.95, 153.886, 153.084, 144.219, 142.95, 135.864, 134.018, 131.14, 129.816, 127.867, 120.775, 107.969, 106.427, 73.1035, 63.8558, 63.3764, 35.8515, 29.2876, 27.1138, 19.4388; IR (film) 2930.8, 28.56.9, 1702.7, 1529.5, 1112.8 crn·1; HRMS (FAB+) m/z calc'd for [C30H33 0 5 Sit: 501.2097, found 501.2105. tert-Butyl Appended Bicycle 41. Prepared using the general procedure for the tandem Stilleoxaelectrocyclization reaction using 14c (87 mg, 0.127 mmol) and 33 (24 rng, 0.106 mmol). Purified by flash chromatography on silica gel (hexanes -7 5:1 hexanes:EtOAc). 67% yield, yellow oil; 1H NMR (300 MHz, CDC1 3) o7.666-7.6352 (comp. m, 4H), 7.435-7.3313 (comp. m, 6H), 5.5386 (s, IH), 4.444 (t, 1=5.3 Hz, 1H), 4.3222 (m, 1=6 Hz, IH), 4.1 835 (m, 1=6 Hz, 1H), 3.06775 (m, 1=5.4 Hz, 1H), 2.8792 (m, 1=5.4 Hz, IH), 2.260 (app. q, 1=5.3 Hz, 2H), 1.118 (s, 9H), 1.04343 (s, 9H); 13C NMR (75 MHz, CDC13) o 172.294, 164.904, 153.152, 135.662, 133.793 , 129.58, 127.621, 105.032, 103.956, 72.8219, 63.6526, 63.4769, 35.6848 , 35.61 , 29.0423, 27.9097, 26.8967, 19.2263; IR (film) 2960.8, 2857.9, 1706.3 , 1542.9, 1113.3 em·'; HRMS (FAB+) m/z calc'd for [C30H370 4 Sit: 489.2461 , found 489.2473. Phenyl Appended Bicycle 42. Prepared by the general procedure for tandem Stille- oxaelectrocyclization reactions using 14b (32.9 mg, 0.046 mmol) and 33 (8.7 mg, 0 .038 mmol). Purified by flash chromatography on silica gel (Hexane -7 5: I Hexane!EtOAc eluent). 92%, yellow oil; 'H NMR (500 MHz, CDC13) o 7.629-7.672 (comp. m, 5H), 7.306-7.418 (comp. m , IOH), 6.249 (s, lH), 4.703 (t, 1=5.5 Hz, IH), 4.387 (comp. m, lH), 4.256 (comp m, 1H), 3.952 (t, J=6 H z, 2H), 3.149 (comp. m, 1H), 3.054 (comp. m, 1H), 2.392 (t, 1=6 Hz, 2H), 1.029 (s, 9H); 13 C J\TMR (125 MHz, CDC13) o 165.027, 159.058, 153.132, 135.868, 133.956, 132.371, 130.731, 129.808, 128.764, 127.865, 126.384, 106.533, 106.394, 73.288, 63.925, 63.603, 35.901, 29.319, 27.109, 19.433; IR (thin film) 2930.6, 2856.8, 1702.9, 1532.1 , 1103.8 em·'; HRMS (FAB+) m/z 1 Mossa, 1. S.; Cassady, J. M.; Antoun, M.D.; Byrn, S.R.; McKenzie, A. T.; Kozlowski, J. F.; Main, P. J. Org. Chern. 1985, 50, 916. 2 Winkler, J.D.; Doherty, E. M. J. Am. Chern. Soc. 1999, 121,7425. 3 Boeckman, R. K.; Ferreira, M. R. R. ; Mitchell, L. H.; Shao, P. J. Am. Chern. Soc. 2002, 124, 190. 4 Stoltz, B. M.; Tambar, U.K.; Kano, T. California Institute of Technology, Pasadena, CA. Unpublished work .. 5 Li, C.; Johnson, R. P.; Porco, J. A., Jr. J. Am. Chern. Soc. 2003, 125, 5095 6 Cole, K. P. ; Hsung, R. P. Tetrahedron Lett. 2002, 43, 8791 7 Malerich, J.P.; Trauner, D. J. Am. Chern. Soc. 2003, ASAP 8 Tohda, Y.; Sonogashira, K.; Hagihara, N. Synthesis 1977, 777. 9 For si milar reaction conditions, see: Nielsen, T . E.; Cubillo de Dios, M . A.; Tanner, D. J. Org. Chern. 2002, 67, 7309-7313. 10 Johnson, C. R. ; Adams, J.P.; Braun, M.P.; Senanayake, C. B. W. Tetrahedron Lett. 1992,33 11 Liebeskind, L. S.; Fengl, R. W. J. Org. Chern. 1990, 55, 5359. 12 Han, X.; Stoltz, B.M. ; Corey, E. J. J. Am. Chern. Soc. 1999, 121, 7600. 13 Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S. J. Org. Chem. 1994, 59, 5905. 14 A. L. Casado, Espinet, P. Organometallics 2003, 22, 1305. t5 16 Han, X.; Corey, E. J. Org. Lett., 1999, I, 1871 For more rigorous calculations of simpler 1,3,5-oxatriene systems, see: Rodriguez-Otero , J.; J. Org. Chern. 1999, 64,6842 - o N -("") I t ~-~ I .......:,_..., 0 8 -Ln - I 0 f N' -< ~ a ~ ("') r rI cu -.. (.) I :c r- t "Q - <.O Q "2 Q) ~ ~ t:::: ~ ...::... 0 c..... I 0 ~ ~ Lee ~ :-' ..::J (...) 0 (/) CL 0 CD 1- l C"l cu a. Ci ') c.:: ~ 2: _:r:: ~ N Q,) ;3 ·O!l t.I.. I 200 180 140 120 100 80 60 J.~-- 40 I I I I I I I I I I l ' n I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I n - 1-rr IT I I I I 160 I I I Figure 2.1 b: JJC NMR Spectrum of Furan Appended Tricycle 3 (75 MHz, CDCl). 20 II I I I I I I I I I I I I I I I I I I II I I I I 3 II 20 I I I I I I I I 0 ppm II I I I II I I I 1 8 1 3.74 22.11 YY ,- , -r -.,--, 39 7 2 . 50 6 '--r---1 - , - ,-,-, 5 2.43 y I 7.92 '-r' 4 5.06 L,-J 3 .-, c...,-' 5.23 Figure 2.2a: 11-J NMR Spectrum of Phenyl Appended Tricycle 39 (500 MHz, CDCI;J. 9 ~--,-,---.---,-. Ph TBDPSO 2 5.31 y 9.59 '-r' 1.98 24.14 1 TY ppm ,- ,- , 220 39 180 160 140 120 100 J Figure 2.2b: uc NMR Spectrum ofPhenyl Appended Tricycle 39 (75 Mllz, C DC/ .). 200 Ph TBDPSO ppm ""' I r ~ u It) 8 N~ ~ f[ 0 <:::> ~ 1.0 - ..0 ""t ...... (!) I c::: :0 § t1l c/) lo.., 0 E ::3 b <.> C!) :J' m ~ c en co .Q ~ 0 en c.. c m 1- ~l ~ ~ ~ :r; CIS ("'\ C'l 0'\ Q) '"' ::1 OJ) t L L ~ 14b 0 180 160 140 120 Figure 2.3b: 13 C NMR Spectrum ofStaiW811C 14b (75 MJ-lz, CD CJ). 200 100 80 60 40 I I I I I I I I I I I I I I ,- r I I I I I I ,, - , I I I I I I I I I I I I I I I I rrn- r rrrrrrTrrr rrt ., I' I rrrrrn I I I I I I I I I I I I I I I I I I I I I I I I I I I II 220 I I I I I I I I I I I I I I I I I I rn.-r 20 0 ppm ~~~·-~ TBDPSO 8 r - l 7 6 1 < 5 F igure 2.4a: 'H NMR Spectrum of Alkynone lOc (300 MHz, CDC/). 9 1 U 10c ------...J ~ O~ OTBDPS 4 m 1 < 3 r--r--r--r-.---, m 2 1 1- r - 1 1 1 1 ppm r---r-11---,--, LJ'"'......___ _ 10c 160 140 120 100 80 60 40 ~~ Figure 2.4b: 13C NMR Spectrum of Alkynonc JOe (75 MHz, CDCJ). 180 ----~~~~~m~~~~~ ~ O~OTBOPS 20 0 ppm '~* r (J) c. 0 CD 1- 0 2£2'6:---211V ' H _ _ __ 2011'92 _ _ __ OTS: 'l 9 _ _ __ LZS'SL- f: 50 ' LL -7======~===­ so·u 69£'011 96L'f:6 _ _ __ lf:'ii'LZl\ 5t5'11ZT\\ 589 6l ~~ ' 9L'il' 6Zt 011Z'f:f:T (/) Q. c ID 5 ..0 0 II 0 'ilf:t''iiLl _ _ __ I 10 8 , -r-,,--r-r-.-.-o--r-r-T~~~ 6 ,-,-r'-r-1 Figure 2.6a: 111 NMR Sp ectrum of Bicyclic Stam1anc 25 (300 MJlz, CDC13). 12 ro-r~~ro-r~~~l'~-ro- 25 C( Bu,Sn~ 0 r _,. J ,--- ,- I II r-· r-1 2 ~1·-,- , r -0 r...,.......,--. ---- ppm Bu,SnD rn I I 160 rrrrrr n I I 140 120 I I I I I I I I I I I I '''T'''--r-T' I 1 -~~ ' . I "" ...., .,.., 100 80 60 40 20 I' I I I r I Tl"T T I r 1 IT I I 1'1111 f ' l l I I I I I I I I I I I I I I I I I ~~~t.~ I I : I Figure 2.6b: 13 C NMR Spectrum of Bicyclic Stannane 25 (75 Mllz, CDC/). 180 I I I I I I1 I I r ~~~~~~~-~~ 25 ({ 0 0 ppm I~·~:·::~ fi..A. •.l.... , _•.uloJ..• ...uo _.oi __. L, .. ,,,,\ N I r I r L N r -qt r r 0 r-t [ 1 1 160 140 1 1 1 1 1 1 1 1 1 120 1 r ]- r r T 1 100 80 60 40 20 ppm '1"-,-,-1 1 1 1 1 1 1 r r r1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 -,-1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 W~l~t~WJ,\~~~~!1\Iut~~MU,.~t Figure 2.7b: 13C NMR Spectrum ofCompound 42 (125 MHz, CDCJ). 180 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 -r~ ..,-,- 1 1 - ~ ~'M~!JMI'~\j~~~)J 9 r-r-' r 8 ~- 14c 0 1 r--r- ~ -snsu. 7 6 I 5 Figure 2.8a: 1H NMR Spectrum ofStarmane 14c (300 MHz, CDCJ). - , - -,---,--- I TBDPSO 4 1- r-1 3 - 1- l 2 1 ~ -· ppm 200 14c 0 180 160 140 120 figure 2.8b: 13C NMR Spcctrwn ofStnnnane 14c (75 MHz, CDClJ. 220 TBDPSO 100 80 60 40 20 0 ppm ~ 0.60. [ r - - .-l f ~N t ~ LM I f F ~ ... f~ ~ ov ....... "'CJ § 0.. '-- - § u t,.... 0 § !::t u cu [ ~ I .... ~ c c 0 ~~ - N~ ~ ~ I... ..._ 8 00 t~ - .......:.. ..., 0 co (I) ~ f- l- 0\ ~ ~ z ~ t..j 0\ c--i ~ ::I .btl ti: 200 180 160 140 120 Figure 2.9b: 13C NMR Spectrum ofCompouncl lB (75 MHz, CDCl.J. 220 18 'D 100 80 60 40 20 0 ppm I I ~ I I N -..'"' '<.J """ lfl 8 N~ ~ ~ 0 0 ~ ID ;- ........ ~ "1::) § 0 Cl. ..... ..... .., 8 ['- Co.., 0 t:l .... E u u ~ ... rv '<t 0 en a.. Cl IX) ..... CX) ~ ~ l :@ ~ ~ ~ 0 0\ ...... C"i II) ~ ~ Figure 2.10b: '-'C NMR Spectrum of Compound 41 (75 MHz , CDCJ). TT""f"' I I' I I I rrm-, T I I fTT'' I I' I I I I' I I I In I I I' I I I I I I I 'l' I I I I' I IT rrrn I rr I r"fTTTTTT I ITTTTI I I' I I I l' rTTTI ' " I ' I I I II I I I I'' 11TJITI 180 160 140 120 100 80 60 40 20 ppm 220 200 0 . .,.. ~~~--~irt~M-IItfpl. . .lfliojril~o,N, 41 r- I 8 1- I 7 6 ~--r- ~ -r ~- 1 5 ,----,- -,----,-----, 4 ~- ~ ~ - -~ 3 ~~J Figure 2.lla: 1H NMR Spectnun oftert-Dutyl Appended Tricycle 30 (300 MHz , CDC/). 9 rr- ~ ~- ~ ___U 2 1 ~ 1 1 ~ -· r -~ r 1 1 ppm 1 200 I I I 180 160 140 120 100 80 60 40 20 0 ppm ~~-~ orrrrn I I I I I I I I I I I I I I I I r· r n 1 1- n I I I I I I I I I I rl I I I I I I I I I I I I rrrn n .]1 I fTTTI r T l l I I I I I I rrr I rrrr I I I I I I I I fTTT"l- Figure 2.1 1b: uc NMR Speclrwn oflert-Bulyl Appended Tricycle 30 (75 MHz, CDCI:J. 220 T""rfl T I I J I I I I I I I I I 12 I 11 10 11~ 1 9 1111111 8 I I I I 7 I I , -1· Figure 2.12a: 'H NMR Spectrum of l odoenone 5a (300 MI-Jz, CDC!/ 13 5a ·~ 0 I 6 I I I I I 5 I I I 1 -, 4 1 1 1 1 1 3 1 1 1 1 2 r1 1 1 1 1 1 1 1 1 1 1 1 r- ppm 1 0 200 180 160 140 120 Figure 2.12b: uc NMR Spectrum of Jodoenone Sa (75 MHz, CDCJ) 220 100 80 60 40 20 0 ppm -~~~-~~-~~~ Sa I~ 0 Index of Compounds Compound 3 Sa 7 9a 9b 9c lOa lOb 10c 13 14a 14b 14c 15 17 18 20 21 25 29 30 32 33 34 35 36 39 40 41 42 Notebook I-197, I281, I-289, II-65, II-245 From TK I-37, I-87,!-217, I-235 , II-97 1-219 I-39, I-59, 1-83, I-175 1-213 I-63, I-221 1-45, I 97, I-225, II-115 I-215, I-223, I-295, TI-95, TI-105 I-127, I-133, I-233 I-53, l-57, I-67, I-69, I-279. II-241 I-245, II-133 I-229, II-69, ll-109, II-153, II-157 I-129, I-139, I-147, I-243 I-27 , I-29, I-31 , I-3 3, I-43 , I-137 II-211 ll-199 II-203 III-37 I-75,1 93, I-109, I-115 , II-67, ll-71 , II-73, II-75, II89, TI-91 , TI-93 , IT- 197 I-239, I-265, ll-3 ll-285 ll-183 II-123 , II-179 ll-187, II-303 ll-201 II-185 ll-215 ll-301, III-41 II-217