Anita E. Mattson

Chiral Silanediols in Anion‐Binding Catalysis

A perfect pair: Silanediols are effective catalysts for the addition of silyl ketene acetals to N-acylisoquinolinium ions. Importantly, this is the first example of a silanediol plausibly participating in anion-binding catalysis, a relatively new direction in the field of hydrogen-bond-donor catalysis. The chiral, enantiopure C2 -symmetric silanediol 1 catalyzes enantioselective transformations.

Silanediol-catalyzed carbon dioxide fixation.

Carbon dioxide is an abundant and renewable C1 source. However, mild transformations with carbon dioxide at atmospheric pressure are difficult to accomplish. Silanediols have been discovered to operate as effective hydrogen-bond donor organocatalysts for the atom-efficient conversion of epoxides to cyclic carbonates under environmentally friendly conditions. The reaction system is tolerant of a variety of epoxides and the desired cyclic carbonates are isolated in excellent yields.

Silanediols: A New Class of Hydrogen Bond Donor Catalysts

Silanediols are introduced as a new class of hydrogen bond donor catalysts for the activation of nitroalkenes toward nucleophilic attack. Excellent yields of product are obtained for the conjugate addition of indole to β-nitrostyrene catalyzed with a stable, storable dinaphthyl-derived silanediol. The preparation and structural characterization of a C(2)-symmetric chiral silanediol is also reported along with its ability to catalyze the conjugate addition reaction.

Internal Lewis acid assisted hydrogen bond donor catalysis.

Boronate ureas are introduced as a new class of noncovalent catalysts for conjugate addition reactions with enhanced activity. Through intramolecular coordination of the urea functionality to a strategically placed Lewis acid, rate enhancements up to 10 times that of more conventional urea catalysts are observed. The tunable nature of boronate ureas is a particularly attractive feature and enables the rational design of catalysts for optimal performance, in terms of both activity and stereocontrol, in new bond-forming processes.

Urea-catalyzed construction of oxazinanes

Highly functionalized oxazinanes are efficiently prepared through urea-catalyzed formal [3 + 3] cycloaddition reactions of nitrones and nitrocyclopropane carboxylates. The reaction system is general with respect to both the nitrocyclopropane carboxylates and nitrones enabling the preparation of a large family of oxazinanes, typically in high yield. This method affords access to enantioenriched oxazinane products through chirality transfer from enantioenriched nitrocyclopropane carboxylates.

A Highly Convergent Approach toward (−)-Brevenal

Progress toward a highly convergent, asymmetric synthesis of brevenal is reported. Construction of the AB-ring and E-ring cyclic ether fragments was achieved through asymmetric alkylation/ring-closing metathesis strategies. A Horner-Wadsworth-Emmons olefination was used in a key bond-forming step to couple the advanced cyclic fragments and enable rapid access to the AB-E ring system.

Arylation of Diazoesters by a Transient NH Insertion Organocascade

It takes two: A unique organocatalyzed cascade for the unsymmetric double arylation of α-nitrodiazoesters is described. This organocascade features the strategic use of carbene-activating anilines in conjunction with a urea catalyst, thus allowing for the synthesis of pharmaceutically attractive α-diarylesters through a transient NH insertion process.

Transition metal and hydrogen bond donor hybrids: catalysts for the activation of alkylidene malonates.

Advances within synthetic organic chemistry have largely led to the development of transition metal catalysis and organic catalysis into two distinct catalyst systems. The combination of these two catalyst systems is a relatively recent, new direction enabling access to useful bond-forming processes that are inaccessible with either catalyst system alone. Driven by the advantageous prospect of combined catalyst systems, we anticipated the design of hybrid catalysts: single molecules containing both transition metal and organocatalytic sites. More specifically, we reasoned that the strategic merger of transition metals and hydrogen bond donor (HBD) catalysts would present opportunities for the development of single catalyst systems benefitting from enhanced activity and unprecedented reactivity. This account describes the successful and strategic incorporation of palladium into a urea scaffold to generate urea palladacycle catalysts (1) for the activation of alkylidene malonates. The inspiration for the development of urea palladacycle catalysis grew from the separate and exceptional successes in the catalytic development of the two key components: palladium and the hydrogen bonding functionality of the urea. Individually, the fields of palladium catalysis and urea catalysis have allowed significant advances in synthetic chemistry, and we reasoned a hybrid palladium–urea catalyst might offer an opportunity to coalesce the best of both fields. Our urea palladacycle design (1) was inspired by boronate ureas (Figure 1), a recently disclosed family of tunable urea catalysts that exhibit enhanced activity when compared with conventional urea catalysts. This improvement in activity is proposed to arise from the increased polarization of the urea functionality as a result of internal Lewis acid coordination. We speculated that similarly placed transition metals on the urea scaffold would give rise to hybrid catalysts with interesting reactive properties. We were particularly excited to explore several specific features of our new hybrid catalysts including: 1) enhanced hydrogen bond donor catalyst activity; 2) tunable ligands and their effect on catalyst reactivity; 3) ease of preparation; 4) stability, and 5) the promising nature of future, bifunctional catalysis involving the enhanced hydrogen bonding site and the transition metal center. To explore the promise of urea palladacycles as a new family of hybrid catalysts, we set out to probe their ability to catalyze the conjugate addition of indole to alkylidene malonates. The activation of alkylidene and arylidene malonates for nucleophilic attack is a useful synthesis technique typically achieved with traditional Lewis acid catalysts like CuACHTUNGTRENNUNG(OTf)2.[8] Conventional ureas and thioureas, although easily able to activate nitroalkenes (2) and a,b-unsaturated imides (3) through proposed hydrogen bonding interactions, have rarely been reported as catalysts for alkylidene malonate (4) activation (Figure 2). These few reports rely on bifunctional urea or thiourea catalysts that may operate to activate both the nucleophile and electrophile; no simple ureas have been reported in the activation of alkylidene malonates. Prompted by this lack of reactivity, we considered this process an ideal testing ground to study urea palla-

Urea‐Induced Acid Amplification: A New Approach for Metal‐Free Insertion Chemistry

The enhanced catalytic activity of difluoroboronate ureas proved to be essential as an acidity amplifier to promote metal-free O-H and S-H insertion reactions of α-aryldiazoacetates in high yield. This methodology was found to be generally applicable to a broad substrate scope and presents a conceptually new approach for organocatalytic diazo insertion reactions. Mechanistic investigations suggest that the reaction pathway involves a urea-induced protonation of the α-aryldiazoester.

Urea-Catalyzed N–H Insertion–Arylation Reactions of Nitrodiazoesters

The power of hydrogen-bond donor catalysis has been harnessed to elicit and control carbene-like reactivity from nitrodiazoesters. Specifically, select ureas have been identified as effective catalysts for N-H insertion and multicomponent coupling reactions of nitrodiazoesters, anilines, and aromatic nucleophiles, thereby preparing a variety of α-aryl glycines in high yield. Experimental and computational studies designed to probe the plausible reaction pathways suggest that difluoroboronate ureas are particularly well-suited to catalyze reactions of nitrodiazoesters with a range of anilines through a polar reaction pathway. Urea-facilitated loss of nitrite followed by addition of a nucleophile conceivably generates the observed aryl glycine products.