Synthesis of 2-boron substituted-1,3-dienes and their Diels-Alder/Suzuki cross coupling reactions

Full title: 

Synthesis of 2-boron substituted-1,3-dienes and their Diels-Alder/Suzuki cross coupling reactions

Author: 

Wang, Liqiong

Year: 

2012

Reference type: 

Thesis

ISBN/ISSN: 

9781267625687

Abstract: 

Clerodane diterpenoids represent a large group of secondary metabolites which are distributed widely in nature. Over a thousand members have been isolated to date, many of which possess interesting biological activities: antifeedant, antitumor, antifungal, antibiotic, anti-peptic ulcer and so on. Although synthetic approaches to the trans -clerodanes abound, cis -clerodane syntheses are rare. The long term objective of this research is to make highly reactive dienes which would undergo Diels-Alder (D-A) reactions with sterically crowded dienophiles to construct cis -clerodane compounds.In previous work, 2-boron-1,3-dienes had shown a high propensity toward self D-A dimerization. Different strategies were tried to prepare dienes without dimerization and seven boron substituted dienes were prepared in good yields. The tri-coordinated boron dienes are less stable than the tetra-coordinated dienes because the boron atom is stabilized by donating electron pairs or groups in the latter type. The reactivity of these boron substituted dienes (2-diethanolaminoborate-1,3-butadiene) in D-A and Suzuki cross coupling reactions were tested and evaluated.Testing concluded that in D-A reactions high yields (> 90%) were found in the reactions of boron substituted 1,3-dienes and N-phenyl maleimide at room temperature or lower. The fastest diene (2-diethanolaminoborate-1,3-butadiene) reacted with a t1/2 less than 4 minutes at -10°C. The 2-diethanolaminoborate-1,3-butadiene has a high HOMO energy compared to its BF3 diene counterpart which accelerates its D-A reactions. High regioselectivities (16:1) were found in the D-A reactions of unsymmetrical dienophiles and 2-diethanolaminoborate-1,3-butadiene. Both high yields and regioselectivities were achieved in Suzuki cross coupling reactions of the resulting boron substituted D-A cycloadducts. Using this methodology, 2-diethanolaminoborate-1,3-butadiene is a promising precursor in providing a potential tool to asymmetric synthesis.Three boron substituted dienes reacted with n-phenylmaleimide very quickly, from seconds to 2 hours. All three dienes are stable at 0°C for more than 2 years. The research also revealed that 4 dienes can be used in tandem D-A/Suzuki cross coupling reactions. High yields and good selectivities were obtained. The possible mechanism of tandem reactions showed that Pd(II) acts as a Lewis acid catalyst to catalyze the D-A reaction between boron substituted dienes and dienophiles followed by Suzuki cross coupling reactions. A possible unstable novel intermediate, a palladium substituted diene, was observed in the reaction by NMR.