Structures of Highly Twisted Amides Relevant to Amide N−C Cross‐Coupling: Evidence for Ground‐State Amide Destabilization

Herein, we show that acyclic amides that have recently enabled a series of elusive transition‐metal‐catalyzed N?C activation/cross‐coupling reactions are highly twisted around the N?C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N‐glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α‐carbon atom. The ¹⁵N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground‐state twist as a blueprint for activation of amides toward N?C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non‐planar amide bonds.     

(+)‐Gibberellin C: hydrogen‐bonding pattern of the monohydrate of a non‐racemic pentacyclic diterpenoid

In the monohydrate of the title compound, (+)‐2β,4aα‐di­hydroxy‐1,7‐di­methyl‐8‐oxo‐4bβ,7α‐gibbane‐1α,10β‐di­carb­ox­yl­ic acid‐1,4a‐lactone, C₁₉H₂₄O₆·H₂O, intermolecular hydrogen bonding progresses helically along b from carboxyl to ketone [O?O = 2.694 (5) Å]. The carboxyl and lactone carbonyl groups in translationally related mol­ecules within a helix both accept hydrogen bonds from the same water of hydration. The oxy­gen of this water in turn accepts a hydrogen bond from the hydroxyl group of a third screw‐related mol­ecule in an adjacent counterdirectionally oriented helix, yielding a complex three‐dimensional hydrogen‐bonding array. Intermolecular O?H—C close contacts were found to the carboxyl and lactone carbonyls, the hydroxyl, and the water.     

Phenyl‐ and mesitylglyoxylic acids: catemeric hydrogen bonding in two α‐keto acids

α‐Oxo­benzene­acetic (phenyl­glyoxy­lic) acid, C₈H₆O₃, adopts a transoid di­carbonyl conformation in the solid state, with the carboxyl group rotated 44.4 (1)° from the nearly planar benzoyl moiety. The heterochiral acid‐to‐ketone catemers [O?O = 2.686 (3) and H?O = 1.78 (4) Å] have a second, longer, intermolecular O—H?O contact to a carboxyl sp³ O atom [O?O = 3.274 (2) and H?O = 2.72 (4) Å], with each flat ribbon‐like chain lying in the bc plane and extending in the c direction. In α‐oxo‐2,4,6‐tri­methyl­benzene­acetic (mesityl­glyoxy­lic) acid, C₁₁H₁₂O₃, the ketone is rotated 49.1 (7)° from planarity with the aryl ring and the carboxyl group is rotated a further 31.2 (7)° from the ketone plane. The solid consists of chiral conformers of a single handedness, aggregating in hydrogen‐bonding chains whose units are related by a 3₁ screw axis, producing hydrogen‐bonding helices that extend in the c direction. The hydrogen bonding is of the acid‐to‐acid type [O?O = 2.709 (6) and H?O = 1.87 (5) Å] and does not formally involve the ketone; however, the ketone O atom in the acceptor mol­ecule has a close polar contact with the same donor carboxyl group [O?O = 3.005 (6) and H?O = 2.50 (5) Å]. This secondary hydrogen bond is probably a major factor in stabilizing the observed cisoid di­carbonyl conformation. Several intermolecular C—H?O close contacts were found for the latter compound.     

The gold(III) tetra­chloride salt of L‐cocaine

The title salt, methyl (1R,2R,3S,5S,8S)‐3‐benzoyl­oxy‐8‐methyl‐8‐aza­bicyclo­[3.2.1]octane‐2‐carboxyl­ate tetra­chloro­aurate(III), (C₁₇H₂₂NO₄)[AuCl₄], has its protonated N atom intra­molecularly hydrogen bonded to the O atom of the methoxy­carbonyl group [N⋯O = 2.755 (6) Å and N—H⋯O = 136°]. Two close inter­molecular C—H⋯O contacts exist, as well as five C—H⋯Cl close contacts. The [AuCl₄]⁻ anion was found to be distorted square planar.     

()‐3‐Ethyl‐2‐methyl‐4‐oxo­cyclo­hexane­carboxyl­ic acid: catemeric hydrogen bonding in a cyclic δ‐keto acid

In the title compound, C₁₀H₁₆O₃, the two mol­ecules of the asymmetric unit form acid‐to‐ketone hydrogen‐bonded chains. The two species differ only very slightly and are related by a pseudo‐center, so that the apparent translational relationship among the units of the hydrogen‐bonded chain is actually a pseudo‐translation, with the mol­ecules alternating in type. Two counterdirectional pairs of chains proceed through each cell [O⋯O = 2.743 (2) and 2.683 (2) Å, and O—H⋯O = 171 (3) and 157 (3)°]. Three intermolecular C—H⋯O close contacts were found, involving all three O atoms of one of the mol­ecules.