Metalated Nitriles:  Cation-Controlled Cyclizations

Abstract

Judicious choice of cation allows the selective cyclization of substituted gamma-hydroxynitriles to trans- or cis-decalins and trans- or cis-bicyclo[5.4.0]undecanes. The stereoselectivities are consistent with deprotonations generating two distinctly different metalated nitriles: an internally coordinated nitrile anion with BuLi, and a C-magnesiated nitrile with i-PrMgCl. Employing cations to control the geometry of metalated nitriles permits stereodivergent cyclizations with complete control over the stereochemistry of the quaternary, nitrile-bearing carbon.

Stereodivergent Quaternization of 2‐Alkyl‐2‐p‐tolylsulfinylacetonitriles: NMR Spectroscopic Evidence of Planar and Pyramidal Benzylic Carbanions

“…It agrees with the higher 13 C d value of the carbanionic carbon observed for 3 a-I' (d = 46.6 ppm) than for 3 a-I (d = 40.6 ppm). In turn, the observed 13 C d value for the cyano carbon signal of 3 a-I' resonates at higher field (d = 134.0 ppm) than that of 3 a-I (d = 137.0 ppm), as expected by the electron-withdrawing effect of the K + on the electronic cloud of the cyano moiety.…”

“…This delocalization is particularly significant on the aromatic NMR-spectroscopy-sensitive nuclei at ortho (6' and 2') and para (4') positions, with respect to the benzylic fragment. Indeed, it is even more evident for the 13 C NMR spectroscopic resonances, as deduced from the HSQC and HMBC experiments. Hence, the carbanionic species show important variations of the chemical shifts of the nuclei at the para position (DdA C H T U N G T R E N N U N G (C-4) ranging between À23.3 and À24.9 ppm and DdA C H T U N G T R E N N U N G (H-4) ranging between À1.8 and À2.0 ppm).…”

“…Additionally, as far as 13 C dA C H T U N G T R E N N U N G (C-6') values for 3 a-I and 3 a-II are concerned, their highfield chemical shifts, relative to that for 3 a-I', may be a consequence of their 1,3-parallel interaction with the methyl group in their presumably proposed more stable conformation [22] (see Figure 1). 3) The relatively low-field chemical shift of H-3' (d = 7.35 ppm) in 3 a-I, relative to that of 3 a-I' (d = 6.90 ppm), can also be accounted for by the anisotropic effect of the S À O bond, which is coplanar to the aromatic ring in 3 a-I.…”

“…To verify the viability of such a proposal, we decided to study the alkylation of 2-alkyl-2-[(2-p-tolylsulfinyl)phenyl]acetonitriles 3 (Scheme 1) under different conditions, which would provide a ready access to the a,a-dialkylphenylacetonitrile fragment, present in biologically active molecules, in either of its two possible configurations. Compounds 3, with intermediate structures between those of 1 and 2, were chosen for this study because marked conformational constrains of differently metalated nitriles have been reported recently as responsible for their stereodivergent evolution in intramolecular [13] and intermolecular [14] alkylation processes. Results obtained in this study are herein reported.…”

“…In addition to these variations, there are other ones that are clearly indicative of the formation of benzylic carbanions. This is the case of the 13 C NMR spectroscopic signal of the benzylic carbon atoms (Figure 2), which resonate at much lower field (d = 40.0-46.6 ppm) than the equivalent signal for 3 a (d = 26.8-27.1 ppm), and the strong deshielding of the CN group (Dd ranging between + 12.3 and + 17.3 ppm) and the ipso carbon C-1' (Dd ranging between + 8.0 and + 12.0 ppm). Taking into account the above-mentioned precedents, these variations allow us to conclude that species 3 a-II, 3 a-I, and 3 a-I' have a carbanionic structure.…”