Alkylidene carbenoids

Bis(pinacolato)diboron reacts with 1-halo-l-lithioalkenes, that is, alkylidene carbenoids, affording 1,1-diboryl-1-alkenes in good yields (Scheme 9).76 The reaction proceeds via formation of a borate intermediate, which is followed by 1,2-migration of the boryl group with elimination of the bromo group. 

This reaction apparently proceeds by way of the normal phosphonate condensation product, the diazoalkylidene, which then spontaneously loses nitrogen to form the transient alkylidene car-bene. Careful work showed that, after statistical corrections were applied, the reactivity of a C-H bond toward insertion was approximately 0.003 for primary C-H bonds (methyl), 1.0 for secondary C-H bonds (methylene), 7.5 for benzylic (methylene) C-H bonds and 18.6 for tertiary C-H bonds. These relative reactivities are very similar to those previously observed for intramolecular C-H insertion by an alkylidene carbenoid generated from a vinyl bromide27. It was shown subsequently that the alkylidene carbene insertion reaction proceeds with retention of absolute configuration28. Using this approach, (l )-3-dimethyl-3-phenyl-l-cyclopentene and (i )-4-methyl-4-phenyl-2-cyclohexcnonc were prepared in high enantiomeric purity. 

The insertion reactions described above probably proceed via the free alkylidenes. The analogous alkylidene carbenoids also insert efficiently into remote C.-H bonds. It has been demonstrated that such alkylidene carbenoids are conveniently generated from the corresponding iodinium tosylates29. Depending on the substitution pattern employed, either [5 + 0] cy-clization or [2 + 3] cyclization can be obtained. 

The methylation of sulfoximines 45 with Me30BF4 proceeded readily and gave the corresponding cyclic aminosulfoxonium salts 46 in quantitative yields. Upon treatment with LiN(H)t-Bu first at-78 °C and then at room temperature, salts 46 delivered the enantio- and diastereomerically pure bicyclic 2,3-dihydrofurans 50 cleanly in high overall yields. It is proposed that the reactions of the aminosulfoxonium salts 40 and 46 with the lithium amide at low temperatures afford the vinyl aminosulfoxonium ylides 41 and 47, respectively. These alkylidene carbenoids eliminate sulfinamide 35 at higher temperatures with formation of the alkylidene carbenes 42 and 48, respectively. Subsequently, the alkylidene... 

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

Alkylidene carbenoids are sp carbenoids and are known to be very interesting reactive intermediates. The most famous reaction of alkylidene carbenoids is the Fritsch-Buttenberg-Wiechell rearrangement (equation 33) . ... 

In 1993, Satoh and coworkers reported the preparation of lithium- and magnesium-aUtylidene carbenoids from 1-chlorovinyl phenyl sulfoxides by sulfoxide-metal exchange reaction at low temperature (Scheme 6). 1-Chlorovinyl phenyl sulfoxide (128) is easily synthesized from the corresponding aldehyde and chloromethyl phenyl sulfoxide in high yield. Sulfoxide 128 was treated with f-BuLi in THF at —78 °C to give the terminal alkyne 131. Obviously, the intermediate of this reaction was the alkylidene carbenoid 129. 

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. 

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