Dehydroiridodiol

In the cyclopentanoid monoterpene family, compounds containing an iridoid-structure exhibit various bioactivities in Nature. For example, dehydroiridodiol, isolated from dry leaves of the cat-attracting plant Actinidia polygama Miq., is known to be an attractant for the male adults of the Chrysopidae and shows activity in amounts as small as lO"" pg [35]. Dehydroiridodial, a more oxidized product, was isolated as a pungent principle of Actinidia polygama Miq. and was characterized by T. Sakan et al. in 1978 [36]. 

Besides the synthesis of racemic dehydroiridodiol [37], some ex-chiral-pool syntheses using (S)-limonene have been described [38]. Dehydroiridodial was synthesized in the same manner [39]. Since the increasing number of cyclopentanoid natural products and their interesting biological activity has stimulated considerable interest in the synthesis of such compounds, we have used our methodology to provide a new asymmetric synthesis of dehydroiridodial, dehydroiridodiol, as well as analogues [40]. 

The methyl group was introduced by a two-step procedure. Thus, the hydrazone Michael adducts 52 were converted into the enol pivaloates 53 in excellent yields and diastereomeric excesses de > 96%) by treatment with pivaloyl chloride and triethylamine. After treatment with lithium dimethylcuprate the chiral auxiliary was removed by addition of 6n HCl in order to obtain the 5-substituted 2-methylcyclopentene carboxylate 54 in good yields and with excellent stereoselectivity (de, ee > 96%). Finally, the asymmetric synthesis of dehydroiridodiol (55, R = Me, = H) and its analogues was accomplished by reduction of 54 with lithium aluminum hydride or L-selectride leading to the desired products in excellent yields, diastereo- and enantiomeric excesses (de, ee > 96%). 

Since the primary alcohol groups of dehydroiridodiol can be converted to the corresponding aldehydes, a pathway to dehydroiridodial (56) could be opened by Swern oxidation in excellent yield as well (Scheme 1.2.13). 

Diastereoselective Michael additions of enolates, prepared from the chiral amides (127) and (128), to prochiral a.p-unsaturated esters were utilized in the synthesis of (+)-dehydroiridodiol (129) and its isomer (130 Scheme 49).143... 

The stereochemical assignments of the products were confirmed and the technology developed was demonstrated by the synthesis of (+ )-aromatin, ( )-isodehydroiridodiol, and ( )-dehydroiridodiol. These synthetic pathways are shown in Scheme 43. 

Et3B as a simple radical initiator was first discovered in hydrostannylation of alkynes [5], The reactions were performed at room temperature or below in the presence of a trace amount of oxygen (Scheme 2). Hydrostannylation was applied to the synthesis of dehydroiridodiol (1) and a-methylene-y-butyrolactone (2). Et3B-induced radical addition reactions of triphenylgermane [7], tris(trimethylsilyl)silane... 

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