Lithium carbenoids generation

Ring expansion of silacyclobutanes. The lithium carbenoid generated from LDA-CH2I2 inserts into the cyclic C-Si bond to give 2-iodosilacyclopentanes, which have found some interesting synthetic applications. 

It appears that neither the lithium carbenoid pathway nor the cyclopropanation of buta-trienes are general routes to [3]radialenes. More successful is the cyclotrimerization of 1,1-dihaloalkenes via copper or nickel carbenoids, provided the substituents at the other end of the C=C double bond are not too small. Thus, tris(fluoren-9-ylidene)cyclopropane 27 was formed besides butatriene 28 from the (l-bromo-l-alkenyl)cuprate 26 generated in situ from (9-dibromomethylene)fluorene (Scheme 3)10. The cuprate complexes formed... 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

III. LITHIUM CARBENOIDS AS REACTIVE INTERMEDIATES IN SYNTHESIS A. Generation of Lithium Carbenoids... 

Due to the acidifying effect of a second halogen atom, dihalo-snbstituted lithium carbenoids 30 can be obtained by deprotonation of geminal dihaloalkanes, the most frequently applied method for the generation of lithium carbenoids with this snbstimtion... 

Whereas the halogen-lithium exchange is of limited importance for the generation of a-lithiated ethers, the reductive lithiation of 0/S-acetals has been applied more frequently, the versatility being enhanced by remarkable diastereoselective variants. Thus, a single diastereomer of the lithium carbenoid 52 results from the diastereomeric mixture 51 (equation 34) . Representative examples of a-lithiated ethers generated by this method and their reactions with electrophiles are given in Table 4. 

A conversion typical of a-halo-a-lithioaUcanes is the formation of epoxides that results from their reaction with aldehydes or ketones. As illustrated in equation 61, the bromo-lithium carbenoid is usually generated by halogen-lithium exchange. The intermediate lithium aUcoxide 113 undergoes an in situ ring closure to give the oxirane 114 . 

The dibromoalkene S-40 can be prepared from S-ethyl lactate by introduction of the MEM (methoxyethoxymethyl) protecting group, reduction to the O-protected lactaldehyde and Corey-Fuchs carbonyl olefination (Scheme 19). The l -enantiomer of 40 is available analogously from f -isobutyl lactate and serves as the reagent in the enantiomeric series. The lithium carbenoid S-41 is generated from S-40 by treatment with n-butyllithium in diethyl ether and reacted with aliphatic and aromatic aldehydes in tetrahydrofuran. High diastereoselectivities are reached, as shown in Scheme 19 . ... 

Reactions of halogen-stabilized carbenoids with imines have been carried out using preformed lithium species e.g. equation or via a carbenoid generated from diiodomethane utilizing zinc-copper... 

Reactions of halogen-stabilized carbenoids with imines have been carried out using prefoimed lithium species (e.g. equation 36), or via a carbenoid generated from diiodomethane utilizing zinc-copper couple (Simmons-Smith conditions). A stereospecific ring closure is observed after the addition of lithiodichloromethane to a benzaldimine (equation 37).The addition of lithiochloro(phenylsulfon-yl)methane to aromatic imines affords 2-phenylsulfonyl-substituted aziridines, which can be deproton-ated and alkylated in excellent yield (Scheme 20). 

Carbene (or carbenoid), generated via reaction of lithium diisopropylamide with 1,1-di-chloro-2-methyl-2-phenylpropane, did not form a 1,3-C-H insertion product, but yielded an alkene, via 1,2-Ph migration, instead. ... 

Allene and its derivatives react with the chloro(methyl)carbenoid, generated with butyllithium, and gives both mono- as well as diadducts. A significant amount of the adduct of chloro(methyl)carbenoid to hex-2-ene was formed hex-2-ene results from the reaction of butyl-lithium with 1,1-dichloroethane. For example, formation of 3-7 and 8-10. 

Note added in proof. ktotA synthesis of (-)-xialenon A using bicyclic alcohol 77 [Eq. (26)] represents the first application of enantioselective a-hthiation transannular C-H insertion of epoxides in natural product synthesis [78]. The first enantioselective generation - intermo-lecular nucleophile trapping of a lithium carbenoid has been described, via enantioselective a-deprotonation of the epoxides of oxa- and aza-bicyclic alkenes [e.g. 93 Eq. (30)] using alkyl-lithiums in the presence of (-)-sparteine or bisoxazoline 5 [Eq. (3)] [79]. Insertion of a second... 

The originally formed 1,3-biradical is an interesting species in its own right because it is also vinylcarbene. Such species were generated independently from diazo compounds and as lithium carbenoids and were shown to give cyclopropenes (Scheme 4.8). ... 

The chemistry of lithium carbenoids has been reviewed by Kobrich, who has also reported the preparation of the anti-Bredt olefin (65). The vinylidene carbenoid, which was generated by reaction of (64) with methyl-lithium,... 

Vinylidenecarbene or allenylidene3 (R)2C=C=C has a lance-shaped, unsubstituted and sp-hybridized carbene center and, therefore, will not be easily subject to steric hindrance in its insertion reactions. On this assumption, (2-methyljpropenylidenecarbene or its carbenoid was chosen as a prototype of typical vinylidenecarbenes and its insertion reaction with several different types of alkoxides was investigated by employing two methods (A and B, Scheme 10) for carbene generation.20 The insertion products 20 were obtained almost exclusively except lithium allyloxide (Table 4, entry 10).21 By-products such as propargyl ether and allenyl ether were not formed at all. To be noted here, in... 

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