Synthesis of Highly Functionalized Bismacycles via Post-Transmetallation Modification of Arylboronic Acids

Bismacycles featuring a sulfone-bridged scaffold have recently been developed as versatile and convenient electrophilic arylating agents. Here, we report that the exocyclic aryl group, which is ultimately transferred to a nucleophilic coupling partner, can be functionalized through cross-coupling, heteroatom substitutions, oxidations and reductions, and protecting group manipulations. This “postsynthetic modification” approach provides concise and divergent access to complex aryl bismacycles. The utility of the functionalized bismacycles in electrophilic arylation of C–H and O–H bonds is demonstrated

Synthesis of Highly Functionalized Bismacycles via Post-Transmetallation Modification of Aryboronic Acids

Bismacycles featuring a sulfone-bridged scaffold have recently been developed as versatile and convenient electrophilic arylating agents. Here, we report that the exocyclic aryl group, which is ultimately transferred to a nucleophilic coupling partner, can be functionalized through cross-coupling, heteroatom substitutions, oxidations and reductions, and protecting group manipulations. This “postsynthetic modification” approach provides concise and divergent access to complex aryl bismacycles. The utility of the functionalized bismacycles in electrophilic arylation of C−H and O−H bonds is demonstrated

Interpreting ancient food practices:Stable isotope and molecular analyses of visible and absorbed residues from a year-long cooking experiment

Chemical analyses of carbonized and absorbed organic residues from archaeological ceramic cooking vessels can provide a unique window into the culinary cultures of ancient people, resource use, and environmental effects by identifying ingredients used in ancient meals. However, it remains uncertain whether recovered organic residues represent only the final foodstuffs prepared or are the accumulation of various cooking events within the same vessel. To assess this, we cooked seven mixtures of C3 and C4 foodstuffs in unglazed pots once per week for one year, then changed recipes between pots for the final cooking events. We conducted bulk stable-isotope analysis and lipid residue analysis on the charred food macro-remains, carbonized thin layer organic patina residues and absorbed lipids over the course of the experiment. Our results indicate that: (1) the composition of charred macro-remains represent the final foodstuffs cooked within vessels, (2) thin-layer patina residues represent a mixture of previous cooking events with bias towards the final product(s) cooked in the pot, and (3) absorbed lipid residues are developed over a number of cooking events and are replaced slowly over time, with little evidence of the final recipe ingredients

Enantioselective Synthesis of α‑Allyl-α-aryldihydrocoumarins and 3‑Isochromanones via Pd-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

An enantioselective Pd-catalyzed DAAA of α-aryl-β-oxo esters has been developed employing the (<i>R,R</i>)-ANDEN-phenyl Trost ligand to prepare a series of α-aryl-α-allyldihydrocoumarins and 3-isochromanones. A variety of aryl groups were successfully employed to afford the dihydrocoumarin and 3-isochromanone products in high yields up to 95% and ee’s up to 96%. Under these conditions, substrates containing di- and mono-<i>ortho</i>-substituted aryl groups gave the highest levels of enantioselectivities. This work represents the first example of the enantioselective preparation of all-carbon quaternary α-allyl-α-aryl dihydrocoumarins and 3-isochromanones

Enantiodivergent Synthesis of Tertiary α‑Aryl 1‑Indanones: Evidence Toward Disparate Mechanisms in the Palladium-Catalyzed Decarboxylative Asymmetric Protonation

Herein, we describe a study into the scope and origin of an enantiodivergent effect in the palladium-catalyzed decarboxylative asymmetric protonation. By switching the achiral proton source, both enantiomers of a series of tertiary α-aryl-1-indanones are readily accessed from the corresponding α-aryl-β-keto allyl esters. In this example of dual stereocontrol, enantioselectivities up to 94% (<i>S</i>) and 92% (<i>R</i>) were achieved using Meldrum’s acid and formic acid, respectively. In an attempt to rationalize this switch in absolute configuration an investigation of the ambiguous mechanism of the decarboxylative asymmetric protonation was conducted. A novel catalytic cycle for the reaction with formic acid is proposed and subjected to a variety of experimental studies

Highly Enantioselective Construction of Sterically Hindered α‑Allyl-α-Aryl Lactones via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Pd-catalyzed decarboxylative asymmetric allylic alkylation has been developed for sterically hindered α-aryl, β-oxo-allyl ester lactone substrates. Pb-mediated α-arylation of the β-oxo-allyl ester was used as the key step to synthesize the substrates for catalysis in moderate to high yields. Optimization studies for decarboxylative asymmetric allylic alkylations (DAAA) were conducted using δ-valerolactone-derived α-aryl β-oxo-allyl ester with 2,4,6-trimethoxyphenyl as the aryl substituent. Using (<i>R,R</i>)-ANDEN-phenyl Trost as the chiral ligand, enantioselectivities of up to >99% ee and 98% ee were achieved with the six-membered and five-membered lactone substrates, respectively. Bulky aryl groups containing di-<i>ortho</i> substitutions and naphthyl groups gave the highest enantioselectivities. This synthetic route allows for the simple modification of aryl groups, giving highly enantioselective access to important structural motifs

Catalytic Asymmetric Synthesis of Sterically Hindered Tertiary α‑Aryl Ketones

The catalytic asymmetric synthesis of a series of tertiary α-aryl cyclopentanones and cyclohexanones has been accomplished via a Pd-catalyzed decarboxylative protonation of the corresponding α-aryl-β-keto allyl esters. Enantioselectivities of up to 92% <i>ee</i> and 74% <i>ee</i> were achieved for cyclopentanone and cyclohexanone substrates, respectively. The route described gives access to these important structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second direct approach for the preparation of tertiary α-aryl cyclopentanones. The synthetic approach allows for simple modification of the aryl group. Significantly, substrates containing sterically hindered aryl groups gave the highest levels of enantioselectivity, and these aryl groups were readily installed by a Pb-mediated arylation of a β-keto allyl ester

Diastereofacial π‑Stacking as an Approach To Access an Axially Chiral P,N-Ligand for Asymmetric Catalysis

A phosphino-imidazoline (PHIM) ligand possessing axial chirality is prepared in a straightforward five-step synthesis. Configurational stability around the chiral axis is achieved by the diastereofacial π-stacking between the pentafluorophenyl and the naphthalene rings. In particular, access to enantiopure ligand (<i>S,S,R</i>_<i>a</i>)-<b>2a</b> was realized by fractional crystallization of the corresponding ∼3:1 atropdiastereomeric mixture. The preliminary application of ligand (<i>S,S,R</i>_<i>a</i>)-UCD-PHIM showed excellent activities in the enantioselective copper-catalyzed A3 coupling (ee’s up to 98.1% and yields up to 98%)