2-Isopropyl-5-oxohexanoic acid is a degradation product of cembrenoids and an important component of the acidic fraction in Oriental tobacco. It produces the hay-like odor and gives slightly grassy smell to smoke. This study is aimed at synthesizing a series of 2-alkyl-5-oxohexanoic acids and their esters and determining the effect of these compounds on cigarette smoke. 4-Diethylamino-2-butanone is obtained by modified Mannich reaction in yields of 70%. Methiodised 4-diethylamino-2-butanone and diethylmalonates are submitted to a thermal-induced Michael addition reaction to synthesize the acids in one step. It is found that 2-isopropyl-5-oxohexanoic acid and its esters have a noticeable effect in organoleptic tests. They enhance and improve the flavour of smoke and reduce the irritation of blended type cigarettes and contribute to flue-cured type cigarettes. Meanwhile it is revealed that the isopropyl radical in C-2 of the acids play an important role in enhancing the flavour of cigarette smoke.