1-Chlorovinyl p-tolyl sulfoxide

A very interesting synthetic method of bicyclo[n.l.O]alkanes from cychc ketones via this 1,3-C,H insertion of magnesium carbenoid as a key reaction was reported (equation 22) . 1-Chlorovinyl p-tolyl sulfoxide (76) was synthesized from cyclopentadecanone and chloromethyl p-tolyl sulfoxide in three steps in high overall yield. Lithium enolate of tert-butyl acetate was added to 76 to give the adduct 77 in quantitative yield. a-Chlorosulfoxide (77) in a toluene solution was treated with i-PrMgCl in ether at —78 °C and the reaction mixture was slowly warmed to 0°C to afford the bicyclo[13.1.0]hexadecane derivative 79 in 96% yield through the reaction of the intermediate magnesium carbenoid 78. 

The synthesis of bicyclo[n. 1.0]alkanes (82) from various 1-chlorovinyl p-tolyl sulfoxides (80) and lithium enolate of ieri-butyl acetate, propionate and hexanoate through the adducts (81) are summarized in Table 3. As shown in Table 3, addition reaction of tert-butyl carboxylates to 1-chlorovinyl p-tolyl sulfoxides (80) proceeds smoothly to afford the adducts (81) in high to quantitative yields. Cyclopropanation of 81 with i-PrMgCl... 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

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) ° . 

TABLE 6. Synthesis of tetrasubstituted olefins (151) by the reaction of 1-chlorovinyl p-tolyl sulfoxide (147) with ArMgBr followed by addition of electrophiles... 

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. 

On the other hand, when this reaction was carried out with 1-chlorovinyl p-tolyl sulfoxide derived from unsymmetrical dialkyl ketone 167 with Af-lithio 1-aminonaphthalene (entries 7 and 8), Z-ortho-alkenylated arylamine Z-171 was obtained as the main product from both vinyl sulfoxides with low stereoselectivity. The stereospecificity and stereoselectivity mentioned above are explained from the high configurational stability of the magnesium carbenoids generated from 1-chlorovinyl p-tolyl sulfoxides derived from a,/ -unsaturated ketones. 

Magnesium alkyUdene carbenoids were found to be reactive with different nucleophiles to give new alkenyhnagnesium compounds which could be trapped with electrophiles. As a whole, novel methods for the synthesis of tri- or tetrasubstimted olefins from the 1-chlorovinyl p-tolyl sulfoxides in a one-pot reaction are realized. 

The stereochemistry of this reaction was also investigated (equation 42). Thus, geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides Z-178 and -178 were synthesized from 4-phenyl-2-butanone and they were treated with t-PrMgCl followed by iV-lithio indole. As shown in equation 42, this reaction gave a mixture of isomers ( -179 and Z-179) in relatively good yields but with low stereoselectivity. 

A new and efficient method for the synthesis of optically active esters and lactones having a tertiary or a quaternary stereogenic centre at the y -position has been developed.28 Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides having two different substituents at the 2-position with the lithium enolate of t -butyl acetate gave optically active adducts in 99% chiral induction from the sulfur stereogenic centre. 

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. 

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... 

---