1.3- Enynes carbolithiation

When butyllithium was added to thioethyl-substituted enyne, a carbolithiation reaction occurs to give the allenyllithium species, which may further react with allylzinc (equation 42). This reaction affords thioalkyl-substituted gem-dimetal66. 

Other internal dienes are not reactive towards carbolithiation, but enynes are. Although the yields are variable, the products are valuable allenyllithiums such as 13.16... 

The addition of lithium organometallics to unfunctionalized conjugated enynes, originally described by Petrov [31] and Miginiac [32], provides the corresponding products in low yields. However, the carbolithiation of silylated enynes was investigated very recently, and it has been found that the presence of silicon reinforces the substantial activation already provided by the enyne system [33], as shown in Scheme 7-33. 

This intramolecular carbolithiation of silylated conjugated enynes was then successfully applied to the construction of small carbocycles such as cyclopropanes and cyclobutanes [35]. Due to the stabilization of the propargylic organolithium after carbocyclization, the reversibility of the intramolecular carbometallation of strained carbocycles was impeded (Scheme 7-37), e.g., for the cyclobutane synthesis. 

Tomida Y, Nagaki A, Yoshida J (2009) Carbolithiation of conjugated enynes with aryllithiums in microflow system and applications to sjmthesis of allenylsilanes. Org Lett 11 3614-3617... 

Tomida Y, Nagald A, Yoshida J (2011) Asymmetric carbolithiation of conjugated enynes a flow microreactor enables the use of configurationally unstable intermediates before they epimerize. J Am Chem Soc 133 3744—3747... 

Scheme 10.15 Carbolithiation/aryl migration of enynes bearing a directing O-carbamate moiety [13].

The carbolithiation- N C aryl migration sequence was performed in TH F, with and without the addition of DMPU, followed by the carbamate cleavage leading to highly substituted propargyl alcohols 47. When the enyne 48 was treated with n-BuLi in toluene without the addition of DMPU, allene products were observed after the protonation step (Scheme 10.16). The addition of (—)-sparteine and carrying out the reaction at —78 °C led to the product 49 as a racemic mixture or at best with moderate enantiomeric excess. 

Scheme 10.16 Synthesis of enantioenriched allenes by intermolecular carbolithiation of enynes 48 [13].

Scheme 10.17 Enantioselective carbolithiation of O-carbamoyl enynes in a continuous flow microreactor system [15].

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