Sequential Double α-Arylation of N-Allylureas by Asymmetric Deprotonation and N→C Aryl Migration

Abstract

On lithiation with lithium amides, N-allyl-N'-aryl ureas undergo rearrangement with transfer of the aryl ring from N to the allylic α carbon. From the α-arylated products, a further aryl transfer under the influence of a chiral lithium amide allows the enantioselective construction of 1,1-diarylallylamine derivatives. Stereoselectivity in these reactions results from the enantioselective formation of a planar chiral allyllithium under kinetic control.

The Mechanism of the Stereospecific Intramolecular Arylation of Lithiated Ureas: The Role of Li+ Probed by Electronic Structure Calculations, and by NMR and IR Spectroscopy

“…LDA has been used experimentally as an alternative to alkyllithiums in rearrangements of more sensitive ureas, [16,19] and is essential for stereospecific rearrangements of the corresponding 1,4-aryl shift in carbamates. [17,18] We note that a crystal structure of an LDA-THF complex [35] shows a dimer with each Li + ion coordinated to a single THF molecule and sharing two amide ligands with the second lithium ion.…”

“…Reactions analogous to this are well known for related carbamates, amides, and allylic ureas. [8,19,36] We employed model M2 and found that the TS (Figure 10) connected to a reactant structure higher in energy (by 43.3 kJ mol -1 ) than R1. This TS is higher in energy than R1 by 102.6 kJ mol -1 , and is thus unfavourable compared with both 1,4-aryl shift reactions.…”

“…Furthermore, related reactions occur with allylic ureas, [19] cyclic ureas, [20] lithiated ureas generated by carbolithiation, [21] and benzylic thiocarbamates. [22] Conversion of the rearranged ureas 7 or carbamates 8 into the amines 9 or alcohols 10 results in an overall stereospecific arylation of an α-methylbenzylamine or α-methylbenzyl alcohol derivative.…”

Advances in the Chemistry of Chiral Lithium Amides

“…CLAs (18a, 22b, 23, 24a, 28, 29, 58, 1.1 equiv) were also shown to effect the enantiotopic deprotonation of benzylsulfonium ions such as 166, leading to a dearomatizing thia-Sommelet rearrangement from which chiral trienes were formed in ee up to 50% (Scheme 10.11, line 3) [42]. As a last reaction in this section, an aryl transfer has been observed under the influence of a CLA (4a, 2 equiv) in the presence of LiCl, which allowed the construction of the enantioenriched urea 168 from 167 (ee up to 88%) with good control of the stereochemistry of a quaternary center (Scheme 10.11, line 4) [43].…”

“…ketones [4c,e,j,o,p,q,r,s, 20-28], (iii) the deprotonation of bridgehead carbons followed by either trapping with an electrophile or β-elimination (and thus a ring opening) [4b,g,h,i,k,l,n, [29][30][31][32][33][34], and (iv) the deprotonation of arylic appendages, directly on the aryl moiety or its benzylic position [4f,m, [35][36][37][38][39]. Few other types of transformations have also been explored, which are mentioned at the end of this chapter [40][41][42][43]. Note that a recent review (2010) by Simpkins and Weller [1b] summarizes the advances made in this field during the period 2000-2010.…”