Hydrogen Bond Assisted l to d Conversion of α-Amino Acids.

l to d conversion of unactivated α-amino acids was achieved by solubility-induced diastereomer transformation (SIDT). Ternary complexes of an α-amino acid with 3,5-dichlorosalicylaldehyde and a chiral guanidine (derived from corresponding chiral vicinal diamine) were obtained in good yield as diastereomerically pure imino acid salt complexes and were hydrolysed to obtain enantiopure α-amino acids. A combination of DFT computation, NMR spectroscopy, and crystal structure provide detailed insight into how two types of strong hydrogen bonds assist in rapid epimerization of the complexes that is essential for SIDT.

Catalytic Stereoinversion of L-Alanine to Deuterated D-Alanine.

A combination of an achiral pyridoxal analogue and a chiral base has been developed for catalytic deuteration of L-alanine with inversion of stereochemistry to give deuterated D-alanine under mild conditions (neutral pD and 25 °C) without the use of any protecting groups. This system can also be used for catalytic deuteration of D-alanine with retention of stereochemistry to give deuterated D-alanine. Thus a racemic mixture of alanine can be catalytically deuterated to give an enantiomeric excess of deuterated D-alanine. While catalytic deracemization of alanine is forbidden by the second law of thermodynamics, this system can be used for catalytic deracemization of alanine with deuteration. Such green and biomimetic approach to catalytic stereocontrol provides insights into efficient amino acid transformations.

Highly stereoselective recognition and deracemization of amino acids by supramolecular self-assembly.

The highly stereoselective supramolecular self-assembly of α-amino acids with a chiral aldehyde derived from binol and a chiral guanidine derived from diphenylethylenediamine (dpen) to form the imino acid salt is reported. This system can be used to cleanly convert D-amino acids into L-amino acids or vice versa at ambient temperature. It can also be used to synthesize α-deuterated D- or L-amino acids. A crystal structure of the ternary complex together with DFT computation provided detailed insight into the origin of the stereoselective recognition of amino acids.

Stereospecific synthesis of a twinned alanine ester.

Reaction between 1,2-bis(2-hydroxyphenyl)-ethylenediamine (hpen) and methyl pyruvate gives the diaza-Cope rearrangement product with good yield and excellent stereospecificity. The product containing two chiral quaternary carbon centers is characterized by high performance liquid chromatography and X-ray crystallography. DFT computation provides insight into why the diaza-Cope rearrangement takes place readily with methyl pyruvate but not with other ketones like acetone and substituted acetophenones.

Understanding the interplay of weak forces in [3,3]-sigmatropic rearrangement for stereospecific synthesis of diamines.

Chiral diamines are important building blocks for constructing stereoselective catalysts, including transition metal based catalysts and organocatalysts that facilitate oxidation, reduction, hydrolysis, and C-C bond forming reactions. These molecules are also critical components in the synthesis of drugs, including antiviral agents such as Tamiflu and Relenza and anticancer agents such as oxaliplatin and nutlin-3. The diaza-Cope rearrangement reaction provides one of the most versatile methods for rapidly generating a wide variety of chiral diamines stereospecifically and under mild conditions. Weak forces such as hydrogen bonding, electronic, steric, oxyanionic, and conjugation effects can drive this equilibrium process to completion. In this Account, we examine the effect of these individual weak forces on the value of the equilibrium constant for the diaza-Cope rearrangement reaction using both computational and experimental methods. The availability of a wide variety of aldehydes and diamines allows for the facile synthesis of the diimines needed to study the weak forces. Furthermore, because the reaction generally takes place cleanly at ambient temperature, we can easily measure equilibrium constants for rearrangement of the diimines. We use the Hammett equation to further examine the electronic and oxyanionic effects. In addition, computations and experiments provide us with new insights into the origin and extent of stereospecificity for this rearrangement reaction. The diaza-Cope rearrangement, with its unusual interplay between weak forces and the equilibrium constant of the reaction, provides a rare opportunity to study the effects of the fundamental weak forces on a chemical reaction. Among these many weak forces that affect the diaza-Cope rearrangement, the anion effect is the strongest (10.9 kcal/mol) followed by the resonance-assisted hydrogen-bond effect (7.1 kcal/mol), the steric effect (5.7 kcal/mol), the conjugation effect (5.5 kcal/mol), and the electronic effect (3.2 kcal/mol). Based on both computation and experimental data, the effects of these weak forces are additive. Understanding the interplay of the weak forces in the [3,3]-sigmatropic reaction is interesting in its own right and also provides valuable insights for the synthesis of chiral diamine based drugs and catalysts in excellent yield and enantiopurity.

Stereoselective recognition of vicinal diamines with a Zn(II) complex.

Zn(II) complex of L (N,N'-bis(2-pyridylmethyl)-N,N'-dimethyl-trans-1,2-diaminocyclohexane) binds chiral vicinal diamines (1,2-diphenylethylenediamine (dpen) and 1,2-diaminocyclohexane (dach)) stereoselectively. Crystallographic studies reveal that the ternary complex has the C2 symmetric cis-alpha topology. 1H NMR shows that the R,R form of the tetradentate zinc complex binds rapidly and reversibly to the R,R form of the diamine over the S,S form with a stereoselectivity of about 5:1. Although the diamine exchange rate is rapid it is slower than the NMR time scale, and distinct signals for the diastereomeric complexes are observed when racemic mixtures of the host and guest molecules are mixed. Origin of stereoselectivity is discussed in terms of steric effects.

A new metal-organic open framework consisting of threefold parallel interwoven (6,3) nets.

Threefold parallel interwoven (6,3) nets were assembled from Ni(II) cyclam complex and 1,3,5-tris[2-(4-carboxyphenyl)-1-ethynyl]benzene. The network generates triangular voids of effective size ca. 18.4 x 14.7 x 9.5 A. It contains 35% free volume of the crystal volume and is stable up to 300 degrees C.

A concise, modular synthesis of chiral peraza-macrocycles using chiral aziridines.

[reaction: see text] Novel chiral peraza-macrocycles were synthesized from chiral aziridines as a common building block. Efficient syntheses of chiral [26]-N(6), [12]-N(4), [9]-N(3), and [14]-N(4) systems were accomplished.