Citronellol from isoprene

The selective telomerization exclusively to natural type terpenoids with a head-to-tail connection has not been achieved so far, but some interesting initial steps have been done. In 1975 Hidai et al. had investigated the synthesis of the terpenoid citronellol starting from isoprene [30]. They reacted isoprene and methanol, yielding the telomer 1-methoxy-... 

Formic acid behaves differently. The expected octadienyl formate is not formed. The reaction of butadiene carried out in formic acid and triethylamine affords 1,7-octadiene (41) as the major product and 1,6-octadiene as a minor product[41-43], Formic acid is a hydride source. It is known that the Pd hydride formed from palladium formate attacks the substituted side of tt-allylpalladium to form the terminal alkene[44] (see Section 2.8). The reductive dimerization of isoprene in formic acid in the presence of Et3N using tri(i)-tolyl)phosphine at room temperature afforded a mixture of dimers in 87% yield, which contained 71% of the head-to-tail dimers 42a and 42b. The mixture was treated with concentrated HCl to give an easily separable chloro derivative 43. By this means, a- and d-citronellol (44 and 45) were pre-pared[45]. 

So far, selective dimerization of isoprene with a palladium catalyst to form natural type terpenoids has not been achieved. The reaction of isoprene with methanol under certain conditions results in a head-to-tail addition product (158). However, the me-thoxy group is introduced at a position differing from that of the oxygen-containing group in natural products61. This telomer is converted to citronellol (159) by the sequence of reactions described in Scheme 4562. ... 

The epoxidation of terpenic substrates is of interest in the flavor and fragrance industry [55,56]. Terpenes are derivatives of isoprene, which has formula CsHg (2-methyl-frans-butadiene). There are tens of examples of terpenes, including limonene, a-pinene, geraniol, citronellol, myrcene, ocimene, camphene, a-terpin-eol, menthol, and isopugelol. Limonene is an abundant monoterpene extracted from citrus oil, which can be epoxidized to obtain fragrances, perfumes, and... 

Precursors for the synthesis of ( + )- and (—)-citronellol (2) are enantioselectively prepared via palladium-catalyzed dimerization of isoprene in the presence of methanol which gives ( )-8-methoxy-3,7-dimelhyl-l,6-octadiene (1) in up to 93 % yield with optical purities of up to 35% when 71-allylpalladium chloride dimer, with the addition of optically active phosphane ligands derived from menthol, is used as catalyst31,32. 

Another way to get citronellol is by the reductive dimerization of isoprene with formic acid and triethylamine using a 1% pcdladium phosphine catalyst [32]. The two head-to-tail dimers are formed in up to 79% yields, which can easily be separated from the head-to-head and tail-to-tail dimers by conversion with aqueous hydrochloric acid, yielding 7-chloro-3,7-dimethyl-l-octene. Hydroboration and pyrolysis of this chloro derivative produces a 1 3-mixture of a- and jS-citronellol. The mono-chloro compound can also be oxidized with tert- mty peracetate and a cuprous bromide catalyst to the chloroacetate, which is reduced with LiAJH4 and pyrolyzed to linalool in 64% overall yield. 

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