Studies towards the total synthesis of lintenone

• Main Author: Price, Richard Alan
• Language: English
• Published: 2009
• Online Access: http://hdl.handle.net/2429/13269

A 32 step synthesis of the racemic compound (1R*,3S*,4R*,7R*,8R*,10R*,11S*)-10-tert butyldimethylsiloxy-4,7,8,ll-tetramethyl-3-triethylsilyoxytricyclo[5.3.1.0⁴‧¹¹]undecane (224) is described. This is a highly advanced intermediate in the attempted total synthesis of racemic lintenone (1). The novel trifunctional reagent 76 was developed and was used to synthesis the series of substituted cyclohex-2-en-ones 104-106 and 78. The substituted cyclohex-2-en-lones 104-106 and 78 underwent copper(I) cyanide mediated intramolecular conjugate addition reactions to give the ketones 112-114 and 71. Ketone 71 was subsequently utilized in the attempted total synthesis of lintenone (1). Ketone 71 was converted into the enone 73. Addition of Me₂CuLi to enone 73 occurred stereoselectively to give the ketone 74. Ketone 74 was subsequently converted into the nitrile 166, which was alkylated stereoselectively with benzyl chloromethyl ether to give the alkylated nitrile 173. Alkylated nitrile 173 was converted into the diazoketone 177. Treatment of diazoketone 177 with dimeric rhodium acetate gave exclusively the tricyclic keto nitrile 178 with complete stereoselectivity. Reduction of the tricyclic keto nitrile 178 with LiAlH₄ followed by immediate protection as the TES ether and then treatment with carbon disulfide and DCC in methylene chloride gave the isothiocyanate 222. Reduction of isothiocyanate 222 with Bu₃SnH and AIBN led to the formation of the tricyclic disilyl ether 224. [formulas not included]