Telomerization of isoprene

Telomerization of Isoprene.—Reviews have appeared on isoprene and chloro-prene, and on the complex reactions of isoprene to form terpenoids (in Japanese). Isoprene reacts with magnesium, especially in the presence of Lewis acids, and the resulting complex gives adducts with aldehydes. As usual in this type of reaction, a very complex mixture is obtained. The palladium-chloride-catalysed reaction of isoprene with acetic acid gives different products in different solvents. Monomers predominate in benzene [2-methylbut-2-enyl acetate (5) and 3-methylbut-2-enyl acetate (6)] while dimers [(7), (8), neryl (9), and geranyl (10) acetates] tend to be formed in tetrahydrofuran. Further details of the synthesis of Cio alcohols from isoprene and naphthyl-lithium are available, as well as of the in situ oxidation,but there is little of novelty (see Vol. 1, p. 17). 

The dimerization of isoprene was carried out by a catalyst system of PdBr2/bis(diphenylphosphino)-1,2-ethane (39) sodium phenoxide at 150°C for I hour in benzene (85). Catalytic activity was enhanced by the addition 

A successful selective head-to-tail telomerization to give 1-methoxy-2,6-dimethyl-2,7-octadiene (89) by the reaction of isoprene with methanol at room temperature was reported by Yamazaki (59). Although the reaction is the selective head-to-tail addition, unfortunately the methoxy group was introduced at the position opposite to oxygen function in natural products  

Hidai and Uchida reinvestigated this reaction. The product was converted to citronellol (90) by the following sequence of reactions (90)  

Asymmetric telomerization of isoprene and methanol by using chiral phosphines, such as menthyldiphenylphosphine, gave an optical yield of 17.6%. The telomerization of methanol and isoprene using w-allylpalla-dium chloride and PBu3 in the presence of sodium methoxide in a mixed solvent of methanol and isopropyl alcohol at room temperature for 2 days produced l-methoxy-2,6-dimethyl-2,7-octadiene (89) (80%) and 1-meth-oxy-2,7-dimethyl-2,7-octadiene (91) (15%) (91). After 2 days, the reaction mixture was heated at 80°C for 8 hours, and 2,6-dimethyl-l,3,7-octatriene (88) (75%) and 2,7-dimethyl-1,3,7-octatriene (85) (14%) were obtained. Also, NiCl2(Bu3P)2 was used as a cocatalyst for the formation of 88. 

The results in Table VI were obtained by the reactions at 80°C with Pd(acac)2 using different ligands in a mixture of methanol and isopropyl alcohol. From these results, it seems likely that reaction temperature has large influence on the regiospecificity of the telomerization. As another example, a mixture of isomeric telomers was obtained by the reaction of methanol and isoprene at 100° (95). 

In contrast to butadiene, isoprene is an vmsymmetrical molecule. The connection of two isoprene molecules can therefore occur on the head h or on the tail t of the molecule. Consequently, in the telomerization of isoprene the tail-to-tail tt)-, tail-to-head th), head-to-tail ht)- and head-to-head (hh)-products are possible. Because the nucleophile HY can attack the chain at positions 1 and 3, eight telomers occur. The fact that the primary telomers possess an iimer-standing double bond means that these molecules exist as cis- and trans-isomers and that, on the whole, twelve different molecules can be formed in isoprene telomerization. 

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- 

6-dimethyl-2,7-octadiene. This telomer was further treated with [NiCl2(PBuf)2] and sodium methanolate as catalyst, yielding 2,6-dimethyl--1,3,7-octatriene. After hydrogenation using a carbonylchromium catalyst such as [Cr(C0)3(PhC02Me)] the 2,6-dimethyl-2,7-octadiene is formed which can be reacted to citronellol by a hydroboration step (Equation 25). 

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. 

Tanaka 2md Hata [33] reported a synthesis of dihydrocitral from isoprene. They started with isoprene and a dialkylamine yielding the 

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The dimerization of isoprene is possible, but the reaction of isoprene is slower than that of butadiene. Dimerization or telomerization of isoprene, if carried out regioselectively to give a tail-to-liead dimer 18 or a head-to-tail... 

Synthetic methods for the production of citroneUal iaclude the catalytic dehydrogenation of citroneUol (110), the telomerization of isoprene (151), and the Utbium-catalyzed reaction of myrcene with secondary alkylamines (128). 

The isomeric N,N-diethylnerylamine could be obtained in 99% isomeric purity (77-86% yield) by telomerization of isoprene with diethylamine in the presence of n-BuLi [215]. 

The telomerization of the lower reactive isoprene with glycerol was achieved in the presence of palladium-carbene complex but in a dioxane/PEG solvent [15]. Under such conditions, both glycerol and PEG are converted. After 24 h, in the presence of 0.06% [Pd(acac)2/IMes.Cl] (1/1.5) at 90°C, the telomerization of isoprene with glycerol (glycerol/PEG/dioxane/isoprene = 1/2.5/2.5/5) yields 70% of the linear monoether glycerol together with 29% of PEG telomer. 

Although various transition-metal complexes have reportedly been active catalysts for the migration of inner double bonds to terminal ones in functionalized allylic systems (Eq. 3.2) [5], prochiral allylic compounds with a multisubstituted olefin (Rl, R2 H in eq 2) are not always susceptible to catalysis or they show only a low reactivity [Id]. Choosing allylamines 1 and 2 as the substrates for enantioselective isomerization has its merits (1) optically pure citronellal, which is an important starting material for optically active terpenoids such as (-)-menthol, cannot be obtained directly from natural sources [6], and (2) both ( )-allylamine 1 and (Z)-allylamine 2 can be prepared in reasonable yields from myrcene or isoprene, respectively, The ( )-allylamine 1 is obtained from the reaction of myrcene and diethylamine in the presence of lithium diethylamide under Ar in an almost quantitative yield (Eq. 3.3) [7], The (Z)-allylamine 2 can also be prepared with high selectivity (-90%) by Li-catalyzed telomerization of isoprene using diethylamine as a telomer (Eq. 3.4) [8], Thus, natural or petroleum resources can be selected. 

Fig. 1 Possible isomers that can be obtained in the telomerization of isoprene with NuH...

Keim W, Kraus A, Huthmacher K, Hahn R (1999) Method and catalysts for the preparation of 6,10- and 6,9-dimethyl-5,10-undecadienyl-2-ones by the telomerization of isoprene with alkyl acetylacetonates. DE 19730546... 

Maddock SM, Finn MG (2000) Palladium-catalyzed head-to-head telomerization of isoprene with amines. Organometallics 19 2684—2689... 

Telomerization of Isoprene with Dialkylamine- N,N-Diethylnerylamine K. Takabe, T. Yamada, T. Katagiri, and J. Tanaka, Department of Synthetic Chemistry, Faculty of Engineering, Shizuoka University, Johoku, Hamamatsu 432, Japan... 

The dimerization of isoprene, particularly whether head-to-tail or tail-to-tail dimers are formed, has been reviewed by Keim et al. Such dimerizations occur in the presence of a nucleophile and a Pd catalyst. The reaction may be accelerated by the use of ultrasound, but generally, tail-to-tail dimers are favored. A few conditions have been found that favor the naturally occurring, head-to-tail skeleton. Behr and Keim have shown that use of trifluoroethanol as the nucleophile resulted in a majority of the ethers 1, while the Cjo fraction from the telomerization of isoprene with its chlorides yielded up to 54% of geranyl chloride (2). Using a more complex Pd catalyst, up to 80% head-to-tail dimers 3 and 4 have been reported. Titanium catalysts with diethylaluminum chloride also yielded a majority of 2,6-dimethylocta-l,4,6-triene (5). ... 

Further studies on the palladium-catalyzed telomerization of isoprene with diethylamine have appeared, one containing the synthesis of a new head-to-head dimer. The butyllithium-catalyzed dimerization in the presence of dimethylamine (or diethylamine) remains the best method for preparing... 

University of Dortmund Telomerization of isoprene with water Pd Water [45 -48]... 

The technical realization of telomerizations is not very well investigated. In a recent paper the telomerization of isoprene with methanol was studied in detail and different concepts of realization were proposed both for single phase operation as well as for biphasic catalysis [115]. One possible alternative proved to be the bipha-sic telomerization with an aqueous methanolic solution as catalyst phase, followed by distillation of unreacted isoprene and methanol, then finally extracting the telomers from the aqueous layer with isoprene. The second alternative for the product separation is without any extraction step and uses only phase separation and distillation steps. 

The Pd-catalyzed telomerization of isoprene with alcohols is an appealing route for the preparation of terpenoid compoimds. Dos Santos and coworkers demonstrated that the catalytic system Pd(OAc)2/SlPr was capable of promoting the trimerization of isoprene producing sesquiterpenes (Figure 4.28) [84]. Switching to IMes promoted the telomerization of isoprene with methanol, resulting in methoxy-dimers with a head-to-head coupling of the isoprene units at unprecedented activity and selectivity. 

It is noteworthy that natural terpenoids have not yet been prepared by selective dimerization of isoprene with Pd or Ni catalysts. Even telomerization of isoprene with methanol does not lead to citronellol since the methoxy group is not located at the proper position the synthesis of the natural isomer requires additional steps [35, 36]. 

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