Catalytic Enantioselective Synthesis of Tetrahydocarbazoles and Exocyclic Pictet-Spengler-Type Reactions

A synthetic strategy for the synthesis of chiral tetrahydrocarbazoles (THCAs) has been developed. The strategy relies on two types of 6-<i>exo-trig</i> cyclization of 3-substituted indole substrates. Enantioselective domino Friedel–Crafts-type reactions leading to THCAs can be catalyzed by chiral phosphoric acid derivatives (with up to >99% ee), and the first examples of exocyclic Pictet–Spengler reactions to form THCAs are reported

Resolution and Determination of the Absolute Configuration of a Twisted Bis-Lactam Analogue of Troger's Base: A Comparative Spectroscopic and Computational Study

The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in a chiral space group P212121 using Cu-irradiation resulting in a very low Flack parameter of -0.06(3), despite the heaviest element being an oxygen atom, thus unambiguously confirming the results from the spectroscopic studies. We conclude that, for the Tröger's base (TB) analogue (2), we may rank the reliability of the individual methods for AC determination as AXRD ≫ VCD > ECD, while the synergy of all three methods provides very strong confidence in the assigned ACs of (+)-(R,R)-2 and (-)-(S,S)-2

Highly Diastereo- and Enantioselective CuH-Catalyzed Synthesis of 2,3-Disubstituted Indolines

A diastereo- and enantioselective CuH-catalyzed method for the preparation of highly functionalized indolines is reported. The mild reaction conditions and high degree of functional group compatibility as demonstrated with substrates bearing heterocycles, olefins, and substituted aromatic groups, renders this technique highly valuable for the synthesis of a variety of cis-2,3-disubstituted indolines in high yield and enantioeselectivity.National Institutes of Health (U.S.) (Award GM46059)Danish Council for Independent Research (Postdoctoral Fellowship

Controlling the stereochemistry and regularity of butanethiol self-assembled monolayers on Au(111)

© 2014 American Chemical Society. The rich stereochemistry of the self-assembled monolayers (SAMs) of four butanethiols on Au(111) is described, the SAMs containing up to 12 individual C, S, or Au chiral centers per surface unit cell. This is facilitated by synthesis of enantiomerically pure 2-butanethiol (the smallest unsubstituted chiral alkanethiol), followed by in situ scanning tunneling microscopy (STM) imaging combined with density functional theory molecular dynamics STM image simulations. Even though butanethiol SAMs manifest strong headgroup interactions, steric interactions are shown to dominate SAM structure and chirality. Indeed, steric interactions are shown to dictate the nature of the headgroup itself, whether it takes on the adatom-bound motif RS•Au(0)S•R or involves direct binding of RS• to face-centered-cubic or hexagonal-close-packed sites. Binding as RS• produces large, organizationally chiral domains even when R is achiral, while adatom binding leads to rectangular plane groups that suppress long-range expression of chirality. Binding as RS• also inhibits the pitting intrinsically associated with adatom binding, desirably producing more regularly structured SAMs

Enantioselective CuH-Catalyzed Reductive Coupling of Aryl Alkenes and Activated Carboxylic Acids

A new method for the enantioselective reductive coupling of aryl alkenes with activated carboxylic acid derivatives via copper hydride catalysis is described. Dual catalytic cycles are proposed, with a relatively fast enantioselective hydroacylation cycle followed by a slower diastereoselective ketone reduction cycle. Symmetrical aryl carboxyclic anhydrides provide access to enantioenriched α-substituted ketones or alcohols with excellent stereoselectivity and functional group tolerance