Allylic Chlorination of Terpenic Olefins using a Combination of MoCl5 and NaOCl

MoCl5 é usado como eficiente agente na cloração alílica de olefinas terpênicas na presença de NaOCl como doador de cloro. Vários terpenóides são convertidos aos cloretos de alila correspondentes em moderados a bons rendimentos em condições reacionais brandas e otimizadas. Diferentes precursores de molibdênio são estudados. Dentre eles, MoO3 fornece bom rendimento, mas depois de um tempo de reação maior.


Introduction
][10][11] Chloride compounds can be prepared directly by bubbling molecular chlorine, but the difficulty of handling chlorine gas limits this procedure. 12Other authors have shown a convenient method for this transformation using solid CO 2 and calcium hypochlorite 13,14 or a combination of Vilsmeier reagent and H 2 O 2 . 15However, this procedure is limited to non acid-sensitive substrates. 15][14][15][16] In line with our continuous interest in the functionalization of natural terpenic olefins, [5][6][7] we report here the result of our investigation on the allylic chlorination using a combination of sodium hypochlorite and molybdenum pentachloride.

Results and Discussion
In order to optimize the allylic chlorination of natural terpenes, b-pinene 1 was chosen as a model substrate (Scheme 1).The reaction was conducted firstly using various concentrations of MoCl 5 in the presence of NaOCl at room temperature in different reaction times (Table 1).
To confirm the role of molybdenum pentachloride, a blank reaction was carried out under similar reaction conditions with b-pinene 1 as substrate.In the presence of NaOCl, no corresponding chlorinated product was observed even after stirring for a long reaction time (entry 1).The same result is observed when using MoCl 5 without NaOCl (entry 2) even at high temperature (80 °C).3][14][15][16] This investigation shows clearly the role of MoCl 5 /NaOCl system in the activation and orientation of the reaction toward the desired product.
As it can be seen in Table 1, the stoichiometry of the reaction is also a key point.Using 0.5 equivalent of MoCl 5 , perillyl chloride 2 was obtained selectively in 67% yield after 30 min (entry 3).The replacement of MoCl 5 by CeCl 3 under similar reaction conditions gives the same product in only 32% yield.When it was used more than 0.5 equiv. of MoCl 5 , both mono-and dichlorinated compounds 2 and 3 were obtained with a variable ratio (entries 4 and 5).At higher amounts of MoCl 5 (2 equiv.), the selectivity decreases considerably (entry 6).
It appears from these results that dichlorinated compound 3 formation is related to the use of high amount of MoCl 5 .In this context, Ceschi et al. 16 have already shown that the conversion of b-pinene to the dichlorinated product was achieved using InCl 3 or CeCl 3 in a longer reaction time.Liu et al. 17 has reported that both a-pinene and b-pinene led to quantitative formation of monochlorinated compounds in DMSO as solvent and phenyldichlorophosphate or phosphorus oxychloride as chlorine donor.It can be noted that the obtained compounds 2 and 3 are chiral with respective optical rotation [a] D 20 = −68 (1.96) and [a] D 20 = −62 (2.01) in agreement with those reported in the literature. 16n order to gain a better insight on this point, a kinetic study was carried out with 1.5 equiv. of MoCl 5 using GC (gas chromatography) to determine the conversion and product distribution (Figure 1).As depicted in Figure 1, the evolution of perillyl chloride 2 and 3 versus time, shows that 2 was formed immediately.This compound reached a maximum after 20 min (62%) and then disappeared in favour of 3 whose amount, insignificant at the early stage of the reaction, rapidly increased after 5 min and then much more slowly after 35 min.This observation proves that perillyl chloride 2 behaves, in the presence of an excess amount of MoCl 5 , as an intermediate that reacts to give the dichlorinated 3, whereas it remains stable when using 0.5 equiv. of MoCl 5 .
A study of the influence of the nature of the molybdenum precursor is reported in Table 2.Among the Mo compounds studied, MoCl 5 appears the most suitable (entry 3).MoO 3 gives good yield but only after a long reaction time (entry 7).In order to confirm the low activity of MoO 3 , other terpenes were checked, such as carvone and limonene with MoO 3 /NaOCl (0.5 equiv. of MoO 3 ) under similar conditions.The reaction took place, although in low yields and after 24 h (30 and 19%, respectively).Other sources of Mo present very low activity (entries 9 and 10).
To assess the scope and limitation of this reaction, different monoterpenes were studied (Table 3).With MoCl 5 /NaOCl system under the optimized b-pinene conditions, all the substrates are converted to the corresponding chlorinated products in good to excellent yields.
a-Pinene 4 gave perillyl chloride 2 selectively (entry 12).However, both mono-and dichlorinated products 2 and 3 were obtained with the increasing of the amount of MoCl 5 (1 equiv.)(entry 13).Entry 14 shows good conversion of limonene 5 to   the same products 2 and 3 in 38 and 21% yields, respectively.The difference of the optical rotation values of 2 and 3 obtained from the chlorination of pinenes and limonene is due to the fact that the ring opening of the pinenes can result in partial racemization.With carvone 6, limonene oxide 8 and geraniol 10, the reaction also works well to give the corresponding monochlorinated derivatives (entries 15-17).

Conclusions
In conclusion, we have described an efficient and facile method for the transformation of naturally occurring monoterpenes to the corresponding allylic chlorides using an inexpensive and readily available Lewis acid (MoCl 5 ).The reaction processes in short reaction time, under mild conditions to afford the expected products in moderate to good yields.A rearrangement of a-pinene and b-pinene to perillyl chloride is observed.Some other molybdenum precursors have been checked and interesting results have been obtained with MoO 3 /NaOCl and b-pinene as substrate.These results lead us to believe that this allylic chlorination method may represent a valuable alternative to the existing procedures reported in the literature.

Experimental
Instruments NMR studies were performed on a Bruker Avance 300 spectrometer in CDCl 3 , chemical shifts are given in ppm

Table 2 .
Allylic chlorination of b-pinene by different sources of molybdenum a Conversion is determined by GC.