Understanding the directed ortho lithiation of (R)-Ph₂P(NCO₂Me)NHCH(Me)Ph. NMR spectroscopic and computational study of the structure of the N-lithiated species

Abstract

A multinuclear magnetic resonance ((1)H, (7)Li, (13)C, (15)N, (31)P) and DFT computational study at the M06-2X(SMD,THF)/6-311+G(d,p)//B3LYP/6-31G(d) level of the structure of a N-lithiated phosphinimidic amide (R)-Ph2P(=NCO2Me)NHCH(Me)Ph 13 has been performed. In THF solution it exists as an equilibrium mixture of monomers and dimers. The monomers consist of a six-membered ring formed by coordination of the lithium atom with the deprotonated nitrogen and the oxygen atom of the carbonyl group. This coordination mode is in contrast to the standard N,N-chelation observed in N-lithiated N,N'-bis(trimethylsilyl)phosphinimidic amides. The calculations showed that the metallacycle adopts a twist-boat conformation and that the lithium atom is in a tetrahedral environment involving O,N-chelation by the ligand and coordination to two/one THF molecules in the monomer/dimer. Dimerization takes place through O-Li bridges. For all species two series of isomers have been identified, which originated by restricted rotation of the methoxy group and ring inversion. The twist-boat conformational interconversion seems to be operating for explaining the pattern of signals observed in the (7)Li and (31)P NMR spectra. The structure found for the most stable dimer is analogous to the molecular structure reported for a related C(α)-lithiated phosphazene 20. The structural study revealed that the chiral side-arm of the N-lithiated species is oriented to the outer face of the pro-S P-phenyl ring, which shows one ortho-proton very close to the nitrogen atom of the carbamate moiety. In this conformation, proton abstraction by a base is highly favoured, in agreement with the experimental results.

Synthesis of P-stereogenic compounds based on the diastereoselective ortho-lithiation of phosphinimidic amides

“…The structural characterization of 10 supports these statements. 21 The chiral amine present in 9 is one of the simplest chiral auxiliaries and both enantiomers are readily available, which warrants access to both antipodes of 12.…”

Synthesis of P-stereogenic diarylphosphinic amides by directed lithiation: transformation into tertiary phosphine oxides via methanolysis, aryne chemistry and complexation behaviour toward zinc(ii)

“…5 We have used a combination of both strategies for accessing P-stereogenic P,P-diarylphosphinimidic amides 2 based on the discrimination of the diastereotopic phenyl rings of the Ph 2 P group through the directed ortho lithiation (DoLi) of a C-chiral substrate 1 (Scheme 1). 7 The products of electrophilic trapping 2 contain additional donor sites at the ortho position, what makes these compounds interesting hybrid ligands. 7 The products of electrophilic trapping 2 contain additional donor sites at the ortho position, what makes these compounds interesting hybrid ligands.…”

Derivatization of (quinolin-8-yl)phosphinimidic amides via ortho-lithiation revisited

“…The apparent insensitivity of the 15 N chemical shift of N11 to the deprotonation is in agreement with the analogous observation for the lithiated nitrogen of complex (R)-2. 11 Unfortunately, no correlations were found for N18 neither in the 1 H, 15 N-nor in the 31 P, 15 N{ 1 H} HMQC spectra of 9. 18 These results, together with the fact that the known X-ray crystal structures of monolithiated phosphinimidic amides 19 consist of a four-membered metallacycle formed by N,N-chelation of the lithium cation, suggest that the anionic system of 9 is acting as an N,N,N-tridentate ligand toward the lithium ion.…”

“…17 The deshielding of C14 promoted by the abstraction of the NH proton of 5 together with the notable decrease of 1 J PC are in agreement with those observed for the N-lithiation of (R)-1. 11 The unequivocal demonstration of the N-lithiated structure of 9 was obtained by the analysis of the 15 N data of compounds 5 and 9 arising from their 1 H, 15 N HMQC spectra (Fig. 1).…”

“…10 The study of the mechanism of this lithiation revealed that mono-deprotonation of 1 afforded the N-lithiated intermediate 2 which exists in a conformation that favours the almost exclusive DoLi reaction of the pro-S P-phenyl ring to give the N,C ortho dianion 3. 11 Scheme 1 C ortho lithiation of phosphinimidic amide (R)-1. † Electronic supplementary information (ESI) available: NMR spectra of the reported compounds, the reaction pathway of NH/CH ortho deprotonation, structures of the most stable monomers and dimers computed and Cartesian coordinates of all the computed structures.…”