Abstract
Extensive attempts to develop a phosphine-catalysed arylation reaction of benzaldehyde Scheme a, to afford benzophenone, employing diaryliodonium salts were unsuccessful. Replacing the phosphine reagents with nitrosobenzene resulted in the formation of azoxybenzene. The use of phenylboronic pinacol ester as the arylating reagent in place of the hypervalent iodine reagent also failed to effect the arylation reaction.An interesting transformation was discovered wherein DMSO was arylated with diphenyliodonium triflate 2.0. The extent of this reaction and the scope was investigated. The highest yield obtained for 2[(methylsulfinyl)methyl]phenol 4.0a was 46% Scheme b. Bis(4-methylphenyl)iodonium triflate 2.3 resulted in the formation of 4-methyl-2-[(methylsulfinyl)methyl]phenol 4.1a in 27% yield. Utilising bis(4-chlorophenyl)iodonium triflate 2.4, phenyl(2,4,6-trimethylphenyl)iodonium triflate 2.6 and phenyl(2,4,6-trimethoxyphenyl)iodonium triflate 2.7 in the foregoing reaction resulted in very low yields of the respective 2-[(methylsulfinyl)methyl]phenols. Dibenziodolium triflate failed to afford the corresponding 2'-iodo-3-[(methylthio)methyl]-(1,1'-biphenyl)-2-ol.
The cyclisation of substituted N-(pent-4-en-1-yl)benzamides to prolinols was readily accomplished using hypervalent iodonium reagents generated in situ. Cyclisation of the model substrate amide 5.0 resulted in 68% yield of prolinol 6.0. A total of 19 amide substrates were subjected to optimised cyclisation conditions and 14 prolinol products were isolated in good to excellent yield and were fully characterised. Pivalamide 5.5, benzenesulfonamide 5.9 and acetamide 5.15 formed the corresponding prolinol product in low yield (<5%), whereas acrylamide 5.6 and chloroacetamide 5.16 failed to afford any prolinol derivatives. The tri-substituted amide 5.20 yielded an interesting bis amide product 6.20 rather than a prolinol Scheme c.
An enantioselective variation of the cyclisation of the N-(pent-4-en-1-yl)benzamide substrates was explored and C2-symmetric pre-catalyst 10.0 was found to give the highest enantiomeric ratio of 78:22 with a yield of 34% for prolinol 6.0. Pre-catalyst 10.0 was prepared via an SN2 reaction starting with methyl 3,5-dihydroxy-4-iodobenzoate 9.1 and triflated lactate 9.3.
| Date of Award | 25 Sept 2025 |
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| Original language | English |
| Supervisor | Mark Heron (Main Supervisor) & Martina Whitehead (Co-Supervisor) |