The synthesis of 4-2H-α-farnesene and 1-2H-α-farnesene

α-Farnesene deuterated at C1 or C4 was synthesised by regiospecific deuteration of 2-geranyl-3-methylsulpholene (2). Treatment of (2) with butyl lithium in dimethylpropenylurea (DMPU) mediated THF resulted in deprotonation at C2. Quenching with D2O/CH3CO2D gave a mixture of deuterated sulpholenes (43-68%). Thermal elimination of sulphur dioxide gave 4-2H-α-farnesene (85%) but with low deuterium incorporation (60%) and poor regiospecificity. Treatment of (2) with butyl lithium in TMEDA mediated THF resulted in deprotonation at C5 with minimal bond migration (1%). Quenching with D2O/CH3CO2D yielded 5-2H-2-geranyl-3-methylsulpholene (75%) which on thermolysis gave 1-2H-α-farnesene (86%) with high regiospecificity and improved deuteration (85%). Some mechanistic aspects of the alkylation of 3-methylsulpholenes are discussed. (Author)