Magnesium alkylidene carbenoids

A. Generation and Nucleophilic Property of Magnesium Alkylidene Carbenoids, the Fritsch-Buttenberg-Wiechell Rearrangement... 

On the other hand, treatment of (Z)-l-chlorovinyl p-tolyl sulfoxide (138) with EtMgCl for 5 min gave a mixture of Z-chloroaUtene 142 accompanied by its ii-isomer (141) in a ratio of 1.8 1. Prolonging the reaction time to 60 min gave an almost equimolar mixture of 142 and 141 in a 1 1.1 ratio. These results indicated that magnesium alkylidene car-benoid 140 isomerizes even at —78 °C. Magnesium alkylidene carbenoid 139 is therefore thermodynamically more stable than 140. 

From a synthetic organic chemistry point of view, the electrophilic nature of magnesium alkylidene carbenoids is much more interesting than their nucleophilic nature. Satoh and coworkers found that treatment of 1-chlorovinyl p-tolyl sulfoxide (147) with an excess of PhMgBr in THF at —85 to —50 °C for 2 h followed by CD3OD gave the deuterio styrenyl derivative 150 in 80% yield with a complete deuterium incorporation (equation 37) ° . 

The electrophilic reaction of magnesium alkylidene carbenoids with other nucleophiles than the original Grignard reagent can also be carried out. For example, treatment of magnesium alkylidene carbenoid 157, derived from 147, with a-sulfonyl lithium carbanion afforded allenes 159 in moderated yields (equation 39/. ... 

A very interesting direct alkenylation of aryiamines at the ortho-position by the reaction of magnesium alkylidene carbenoids with A-lithio aryiamines to give 162 was reported by Satoh and coworkers (equation 40) . Magnesium alkylidene carbenoid 157, derived... 

Very interesting results were obtained from the reaction of magnesium alkylidene carbenoids with mefa-substituted arylamines (Table 8) . The reaction of magnesium alkylidene carbenoids 157 and 161 with three mefa-substituted anilines was carried out and the results are summarized in Table 8. The reaction of 157 with meta-anisidine gave two products 163 and 164 (in a 30 13 ratio) in 43% yield. The main product was found to have the alkenyl group at the more hindered position (163). As shown in the Table, all the other meto-substituted aniline derivatives also gave the more hindered alkenylated compounds as the main product in variable ratio. 

Stereochemistry of this reaction is also quite interesting. Thus, both geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides (165-167) were synthesized from 2-cyclohexenone, methyl vinyl ketone and 2-heptanone respectively, and the corresponding magnesium alkylidene carbenoids were generated and treated with A-lithio aniline or A-lithio 1-aminonaphthalene. The results are summarized in Table 9. 

TABLE 8. Synthesis of ort/to-alkenylated arylamines 163 and 164 by reaction of magnesium alkylidene carbenoids with meta-substituted A-hthio arylamines... 

For a better understanding of the structure and the substitution reactions of magnesium alkylidene carbenoids, computational studies were performed. The result for the calculation of magnesium alkylidene carbenoid 161 is shown in Figure 1, and two different optimized structures were found depending on the basis set used for the theoretical calculations. It seems that the MP2 structure is closer to the reality. 

TABLE 9. The reaction of magnesium alkylidene carbenoids derived from E- and Z-l-chlorovinyl p-tolyl sulfoxides with A-hthio aniline and A-hthio 1-aminonaphthalene... 

TABLE 10. Reaction of magnesium alkylidene carbenoid 157 with A-lithio nitrogen-containing heterocycles... 

TABLE 12. Synthesis of enyne 183 from magnesium alkylidene carbenoids 134a with lithium acetylides and electrophiles... 

Lithium acetylides and lithium thiolates have been shown to add to magnesium alkylidene carbenoids yielding conjugated enynes and vinyl sulfides.94... 

The direct alkenylation of arylamines at the ortho -position with magnesium alkylidene carbenoids has been investigated using both theoretical and experimental approaches." In some cases, the reaction has proceeded in a highly stereospecific manner at the carbon bearing the chlorine and the sulflnyl group. 

Satoh has developed a related sulfoxide-magnesium exchange reaction between aryl a-chloroalkyl- and a-chlorovinylsulfoxides, and has extensively studied the chemistry of the resulting magnesium carbenoids and magnesium alkylidene carbenoids. ... 

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl /)-tolyl sulfoxide 161 with isopropylmagnesium chloride at —78°C in toluene, with AT-lithioindazole 162 (or pyrazole) gave N-alkenylated indazole 163 in moderate yield (Scheme 5) <2005TL4855>. Reaction of lithiopyrazole gave the N-alkenylated pyrazole but in a lower yield. 

The magnesium alkylidene carbenoid generated occurs in equilibrium between... 

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