Chiral Organometallic Reagents, III. On the Configurational Stability of α‐Bromoalkyllithium Compounds

Abstract

The carbenoids 2 undergo at -110°C a bromine/lithium exchange reaction with 1,l-dibromo alkanes. This leads to partial equilibration of the carbenoids 2 during their generation from the 1,l-dibromo compound 1. In the absence of the precursor 1, the carbenoids 2 have been found to be configurationally stable at -110°C.Diastereoselectivity in the formation of the products 3 from the dibromo compound 1 via the diastereomeric carbenoids 2*) depends on the relative magnitude of the various rate constants for (a) the kinetic diastereoselectivity in the exchange of the diastereotopic bromine atoms in 1 ( = kl), (b) the epimerisation of the carbenoids 2 (= k2) and (c) the trapping of the carbenoids 2 by electrophiles (= k3). We report here on investigations to gain a better understanding of the mechanistic aspects of this reaction. Me3Si0Br c --

On the Mechanism and Stereochemistry of Chiral Lithium‐Carbenoid‐Promoted Cyclopropanation Reactions

“…This is in good agreement with the experimental observations that a-bromoalkyllithium compounds are www.chemeurj.org both chemically and configurationally stable over the reaction temperature range of the cyclopropanation reactions. [39] It is interesting that the reaction barriers for the carbometalation mechanism are as high as those relative free energies computed for the formation of free carbenes. This provides further evidence that the carbometalation mechanism is not reasonable for the cyclopropanation reactions of carbenoids 1 and 2.…”

Lithium Carbenoids

“…As shown in equation 8, the reaction is also feasible with configurationally stable α-bromo-α-lithioalkanes 66 This type of cyclobutanone annelation is feasible with various dibromocyclopropanes. When diaryl ketones are used as electrophiles, the oxaspiropentane-cyclobutanone rearrangement occurs spontaneously, so that the cyclobutanone is obtained directly (equation 63) 110,357 .…”

“…At a glance, this result shows that the carbenoid 16 is configurationally stable at −110 • C. When, however, the same carbenoid 16 has been generated by means of a bromine-lithium exchange, partial epimerization leading to 18 occurs (equation 9) 66 . …”

“…Thus, the exo-bromine atom in dibromocyclopropane 25 is exchanged exclusively due to the methoxy substituent, which encourages the lithium to occupy the cis orientation (equation 16) 103 An alternative access to alkyl bromo lithio carbenoids is provided by the tin-lithium exchange reaction, as shown in equation 8 66,74 . When the carbenoid carbon atom is substituted by electron-withdrawing groups like carboxylic ester or keto groups, the carbenoid character is no longer maintained.…”

“…Both the glyceraldehyde-derived bromoalkene 45 The tin-lithium exchange reaction does not play an important role for the generation of 1-halo-1-lithioalkenes. Whereas in α-bromoalkylstannanes tin-lithium exchange occurs upon treatment with n-butyllithium 66 , the bromine rather than the tin is replaced against lithium, when α-bromovinylstannanes are allowed to react with n-butyllithium 196 . …”