Microwave-Assisted Phospha-Michael Reactions with Internal Alkenes

The atom efficient phospha-Michael reaction between bis 4-methylphenyl phosphine oxide and several activated internal alkenes has been shown to occur under microwave irradiation without added solvent or catalyst. The alkenes used for this study were ethyl 4-nitrocinnamate, two chalcones ((E)-3-(4-methoxy-phenyl)-1-(4- nitrophenyl)-prop-2-en-1-one and (E)-1-(4-methoxyphenyl)-3-(3-nitro-phenyl)-prop-2- en-1-one), and 2-phenylmethylene-propanedinitrile. In the case of ethyl 4-nitrocinnamate, reaction with bis 4-methylphenyl phosphine oxide for sixty minutes at 130 °C yielded the desired phospha-Michael product in a 55% yield after purification. Varying the location of the nitro group on the phenyl rings of the chalcones did not seem to have a large effect on their reactivity. By NMR, both chalcones seemed to react to the same extent when the reaction times and temperatures were held constant. Interestingly, a phospha-Michael reaction was observed at a reaction temperature of 65°C for experiments involving 2- phenyl-methylene-propanedinitrile while the other substrates required a reaction temperature of 130 °C. Similar experiments were carried out with bis mesityl phosphine oxide and two internal alkenes: 2-phenylmethylene-propanedinitrile and ethyl-2-cyano-3- methyl-2-butenoate. These experiments did not yield any of the predicted phospha- Michael products, which suggest steric limitations to the Michael donor for this reaction.

Microwave-Assisted Bond Forming Reactions

ABSTRACT FOR PART I: PHOSPHA-MICHAEL ADDITIONS TO ACTIVATED INTERNAL ALKENES: STERIC AND ELECTRONIC EFFECTS A method for the phospha-Michael addition of bis(4-methyl)phenyl phosphine oxide to activated internal alkenes has been developed. Michael acceptors including cinnamates, crotonates, chalcones, and internal alkenes containing multiple activating groups were all successfully utilized in this reaction. The reaction was fairly tolerant of electron-donating and electron-withdrawing substituents on the Michael acceptor, and moderate to excellent yields (49-96%) of the adducts were isolated. When steric bulk was increased by a second substituent on the -position of the Michael-acceptor the reaction was suppressed. This was usually overcome by adding a second activating substituent to the -position. ABSTRACT FOR PART II: MICROWAVE-ASSISTED ARYLGOLD BOND FORMATION A microwave-assisted method was developed for the formation of arylgold complexes containing (2-Biphenyl)di-tert-butylphosphine (JohnPhos) as the supporting phosphine ligand. Arylboronic acids with increasingly bulky aromatic groups were screened to determine the steric limitations of the reaction. Arylgold complexes (JohnPhos)Au(p-methoxyphenyl), (JohnPhos)Au(2,4,6-trimethylphenyl), and (JohnPhos)Au(4-bromo-10-anthracene) were all synthesized by microwave irradiation at 70ºC in the presence of Cs2CO3 in either THF or iPrOH. Reactions performed with arylboronic acids containing unhindered ortho positions were carried out in THF. Arylboronic acids with substituents on the ortho position required iPrOH as the reaction solvent. Arylboronic acids with extreme steric hindrance on the ortho position of the aryl substituent, 2,4,6-triisopropylpphenylboronic acid, were unreactive. It was determined that increasing the irradiation temperature increased the formation of side products, therefore to promote conversion to the arylgold complex the duration of the reaction time was increased while maintaining a temperature of 70ºC. Arylgold complexes (JohnPhos)Au(p-methoxyphenyl), (JohnPhos)Au(2,4,6-trimethylphenyl), and (JohnPhos)Au(4-bromo-10-anthracene) were synthesized with moderate yields (40-69%).