Oxygenated organolithiums chelation

The addition reactions of alkyllithium-lithium bromide complexes to a-trimethylsilyl vinyl sulfones that have as a chiral auxiliary a y-mono-thioacetal moiety derived from ( + )-camphor are highly diastereoselective. A transition state that involves chelation of the organolithium reagent to the oxygen of the thioacetal moiety has been invoked. The adducts are readily converted via hydrolysis, to chiral a-substituted aldehydes22. 

In contrast with unreactive, unfunctionalised terminal alkenes, allylic and homoallylic ethers (22, 24) and alcohols (20) from which the product organolithiums (21, 23, 25) can be chelated in a (preferably) five-membered, oxygen-containing ring, carbolithiate rapidly and cleanly.23 Coordination overrides any preference for the lithium to be bonded to the primary carbon, but cannot overcome the unfavourability of forming a tertiary organolithium - 26 gives 27, but 28 cannot be carbolithiated. Coordination to sulfur in similar thioethers 29 works too. 

Addition of organolithium or organomagnesium reagents to N-methoxy- N-methyl amides gives a tetrahedral intermediate that is stabilized by chelation of the magnesium atom by the two oxygen atoms. This intermediate collapses, to give a ketone, only when acid is added at the end of the reaction. 

Threo diastereoselectivity is consistent with a chelation-controlled (Cram cyclic model) organolithium addition (Figure 8a). Since five-membered chelation of lithium is tenuous, an alternative six-membered chelate involving the dimethylamino nitrogen atom of the thermodynamically less stable (Z)-hydrazone (in equilibrium with the ( )-isomer) cannot be discounted. The trityl ether (entry 4, Table 9) eliminates the chelation effect of the oxygen atom such that the erythro diastereomer predominates (via normal Felkin-Ahn addition) (Figure 8b). 

Pyridine is an aromatic 6n electron heterocycle, which is isoelectronic with benzene, but electron deficient. Nucleophiles thus add almost invariably to carbon C2 of the imine-like C=N double bond. Perhaps the best known nucleophilic addition is the Chichibabin reaction with sodium amide in liquid ammonia, giving 2-aminopyr-idine. Reactions of the quinoline moiety of cinchona alkaloids can be more complex. Although expected 2 -addition can be achieved easily with organolithium reagents to yield 13 (Scheme 12.6) [9], LiAlH4, for example, has been shown to attack C4 en route to quincorine and quincoridine (Schemes 12.4 and 12.5). C4 selectivity is due to chelation of aluminum by the C9 OH oxygen. 

All organolithium and organosodium chelates are extremely reactive toward water, oxygen, polar compounds, etc. They are almost invariably more reactive than the corresponding unchelated compounds. 

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