Heteroconjugate addition

Isobe and coworkers407 found an interesting diastereoselective heteroconjugate addition of methyllithium to 314. The stereochemical control was considered to be determined at the stage of the intermediate 315. Since methyllithium is considered to be coordinated strongly with the methoxyethoxymethoxyl (OMEM) group, the methyl anion would attack the -carbon of the olefin only from one side, as shown below. 

Finally, useful stereoselectivities have been recorded for the heteroconjugate addition of organometallic reagents to 1-silyl substituted vinyl sulfones.22 The synthesis of such sulfones can be achieved starting from phenylthioacetylene.6 1 11 23 The synthesis of the dicobalt hexacarbonyl complex24 and the polymerization of phenylthioacetylene25 have been described. 

This isomerization was used in the heteroconjugate addition to the acyclic system. Therefore, the substituted olefin 72, in which the double bond is conjugated with both sulfone and silicon atoms, undergoes a diastereoselective addition of CHsLi. The resulting lithium alcoholate is quantitatively converted into the silyl ether dianion 73 and the addition of deuterium oxide afforded the functionalized product 74 in excellent yield (equation 16. 

Heteroconjugate addition (9. 311). The diastcrcoselcctive conjugate addition of methyllithium to a secondary allylic alcohol substituted with a SO,C,H, and a Si(CH,)< group to give the. yvn-adduct as the only or major product (equation I) has been extended to other alkyllithiums and used to prepare sytt and u/(//-diastercomcrs with different... 

Heteroconjugate addition. The addition of methyllithium to the heleroalkene 1 is accompanied by high asymmetric induction (>99%) to give 2 in 95% yield, in which Cl and C2 are in the threo orientation. The MEM group is undoubtedly responsible for the stereochemical control by coordination of the oxygen atoms with the lithium reagent. ... 

To return to the retro synthesis in Scheme 7, it was possible to provide the unsaturated aldehyde 56 from the sulfone derivatives 57 and 58 utilizing the function of the sulfonyl group in heteroconjugate addition strategy. 

In the course of total synthesis of maytansine 1 (Fig. 8.1), an ansa-macrocyclic lactam from Maytenus serrata, M. buchananii, etc., the heteroconjugate addition [1-3] of methyllithiiun to the pyranosyl heteroolefin such as 2 (Fig. 8.2) proceeded with the complete acyclic stereoselection [1]. The authors explained the high diastereoselective C-C bond formation by efficient conformational and chelational control. 

Isobe M, Kitamura M, Goto T (1979) Complete asymmetric induction in heteroconjugate addition on an acyclic system. A new synthetic approach directed toward ansamacrolide maytansine. Tetrahedron Lett 36 3465-3468... 

Isobe M, Kitamura M, Goto T (1980) Heteroconjugate addition of lithium alkyls to substituted hetero-olefins conjugated with sulfur and silicon atoms. Chem Lett 331-334... 

Epoxides can also be accessed asymmetrically using hypervalent iodine reagents in combination with imidazolidinone catalysts 78 (Scheme 30). The methodology developed by MacMillan et al. includes participation of hypervalent iodine reagent in a 1,4-heteroconjugate addition reaction for the organocatalytic, asymmetric epoxidation of a,p-unsaturated aldehydes 77. This organocatalytic reaction allows for the enantioselective formation of epoxides 78 from a wide array of electronically and sterically diverse a,p-unsaturated aldehydes [92]. 

Isobe, M., Ichikawa, Y., Bai, D.-I., and Goto, T. (1985) Synthetic studies toward marine toxic polyethers (4). Synthesis of segment A of okadaic acid via anti-selectivity by heteroconjugate addition. Tetrahedron Lett., 26, 5203-5206. 

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