On the control of secondary carbanion structure utilising ligand effects during directed metallation

Andrew E H Wheatley,Jonathan Clayden,Joanna Haywood,Ian H Hillier,Alison Campbell Smith,Mark A Vincent,Laurence J Taylor

doi:10.3762/bjoc.8.5

Andrew E H Wheatley, Jonathan Clayden + Show 5 more

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https://doi.org/10.3762/bjoc.8.5

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Abstract

N,N-Diisopropyl-2-propylbenzamide 6-H undergoes lateral deprotonation by t-BuLi in the presence of the Lewis base PMDTA (N,N,N′,N″,N″-pentamethyldiethylenetriamine) to give a benzyllithium 6-Lil·PMDTA that incorporates a trigonal planar secondary carbanion. In the solid state, the amide directing group and the PMDTA additive work together to abstract the metal ion from the deprotonated α-C of the propyl group (4.107(4) Å). A short distance of 1.376(3) Å is observed between the deprotonated carbon centre and a planar aromatic system that shows a pattern of bond lengths which contrasts with that reported for related tertiary carbanion systems. Analogous benzylic deprotonation is seen if 6-H is treated with t-BuLi in the presence of diglyme to give 6-Lil·DGME. X-ray crystallography now shows that the metal ion more closely approaches the tertiary carbanion (2.418(6) Å) but that the planarity of the deprotonated carbon centre and the bonding pattern in the organic anion seen in the PMDTA complex are retained. DFT analysis corroborates both the short distance between aromatic ring and carbanion centre and the unperturbed nature of aromaticity in 6-Lil·L (L = Lewis base). The observation of two structure-types for the carbanion in solution is explained theoretically and by NMR spectroscopy in terms of cis and trans isomerism imparted by partial double bond character in the arene–(α-C) bond.

Highlights

Directed deprotonative lithiation – where the directing group generally combines inductive electron withdrawal with the presence of an electron-rich metal-coordinating atom [1] – has established itself as an enormously powerful tool for the elaboration of aromatic and heteroaromatic compounds [2,3,4,5,6,7,8,9] and continues to find new applications today [10,11]
Based on our knowledge of the ability of Lewis base solvent or additives to influence the chemoselectivity of lithiation, 6-H was treated at −78 °C with t-BuLi in a hydrocarbon medium to which 1 equiv of PMDTA had been added
Though the analysis of charge delocalisation has recently been undertaken for benzylic tertiary carbanions, revealing a pentadienyl bonding pattern with alternating short and long bonds noted between the deprotonated (α-C) and the aromatic carbon centre para to it, the situation for secondary carbanionic 6-Lil·PMDTA is different

Summary

Introduction

Directed deprotonative lithiation – where the directing group generally combines inductive electron withdrawal with the presence of an electron-rich metal-coordinating atom [1] – has established itself as an enormously powerful tool for the elaboration of aromatic and heteroaromatic compounds [2,3,4,5,6,7,8,9] and continues to find new applications today [10,11]. Consistent with the observation of essentially trigonal planar geometry at C8 in the solid-state structure of 6-Lil·PMDTA (Figure 1), both solution isomers reveal significantly deshielded deprotonated carbon centres.

Results

Conclusion