Chemoselective Synthesis of Unsymmetrical Dithioacetals through Sequential Carbene Insertion and Acetal Exchange of Acylsilanes and Thiols under Visible Light Irradiation.

Dithioacetals are a frequently used motif in synthetic organic chemistry, and most existing reports discuss only symmetrical dithioacetals. Examples of unsymmetrical dithioacetals are scarce, and few general methods for the selective synthesis of these compounds exists. An intriguing visible-light-induced strategy has been established in this work for sequential reactions of S-H insertion and acetal exchange between acylsilanes and two different thiols that deliver a wide variety of unsymmetrical dithioacetals in moderate yields. The unsymmetrical dithioacetals were obtained with high selectivity, and a great variety of functional groups were tolerated.

Friedel-Crafts Reaction of Acylsilanes: Highly Chemoselective Synthesis of 1-Hydroxy-bis(indolyl)methanes and 1-Silyl-bis(indolyl)methanes Derivatives.

A novel double Friedel-Crafts reaction of acylsilanes in water is described. This strategy enables synthesis of bis(indolyl)methane derivatives with 1-hydroxy or 1-silyl substituents in moderate to high yield. Compared to the 1-silyl-bis(indolyl)methane derivatives from indole substrate, 1-hydroxy-bis(indolyl)methane derivatives were synthesized from the 5-hydroxyindole, and the hydrogen bonds in the 5-hydroxyindole play a crucial role in regulating the reaction selectivity.

Nucleophilic Allylation of Acylsilanes in Water: An Effective Alternative to Functionalized Tertiary α-Silylalcohols.

A nucleophilic allylation of acylsilanes in water was developed, generating versatile functionalized tertiary α-silyl alcohols in high yields. With the assistance of hydrogen bonding, a reaction model of less reactive acylsilane was achieved. Unlike the conventional strategy, transition metals and an additional Lewis acid catalyst were not required, and rate acceleration was observed in water.

Organobase-Catalyzed Umpolung of Amides: The Generation and Transfer of Carbamoyl Anion.

A novel organobase-catalyzed umpolung reaction of amides was disclosed. This method provides an efficient method to generate and transfer carbamoyl anions. In this transformation, some of the inherent disadvantages of carbamoyl metal were avoided. The mechanistic analysis revealed that the reaction proceeds through polarity inversion of amide, and various carbamoyl anions were applied in the reaction. Moreover, a wide range of substrates was achieved with moderate to excellent yield.

Hydrogen-Bond-Assisted Sequential Reaction of Silyl Glyoxylates: Stereoselective Synthesis of Silyl Enol Ethers.

A novel hydrogen-bond-assisted sequential reaction of silyl glyoxylates is described. This method provides an efficient strategy for the synthesis of silyl enol ethers with high selectivity. In these transformations, hydrogen bonds from 2-nitroethanol and its derivatives are critical to the stereochemical outcome. Both E- and Z-isomers are achieved via Henry reaction/Brook rearrangement/elimination and Henry reaction/Brook rearrangement/retro-Henry reaction/elimination processes, respectively (up to 99:1 Z-selectivity, and 9.2:1 E-selectivity).

Aqueous ZnCl2 Complex Catalyzed Prins Reaction of Silyl Glyoxylates: Access to Functionalized Tertiary α-Silyl Alcohols.

An efficient Prins reaction of silyl glyoxylates in the presence of an aqueous ZnCl2 complex as a catalyst was developed, providing functionalized tertiary α-silyl alcohols in high yields under mild conditions. A preliminary investigation indicated that the aqueous ZnCl2 complex acted as a dual functional catalyst of Brønsted and Lewis acid to activate the carbonyl groups of silyl glyoxylates via a dual-activation model.

"On Water" Direct Catalytic Vinylogous Aldol Reaction of Silyl Glyoxylates.

The unique reactivity of water in the direct catalytic vinylogous aldol reaction of silyl glyoxylates is reported. With the hydrogen-bonding networks from water, the unfavorable homogeneous reactions in organic solvents were severely suppressed, and the "on water" relay chemistry for the vinylogous aldol reaction was realized in heterogeneous conditions (water as solvent), providing the desired α-hydroxysilanes with a quaternary carbon center in high yields. Moreover, new insights on the role of water in biological systems were demonstrated.

Visible-light-induced deboronative alkylarylation of acrylamides with organoboronic acids.

A visible-light-induced deboronative alkylarylation of acrylamides with organoboronic acids was developed. In this transformation, boronic acids could be activated by the organic photocatalyst of eosin Y, generating alky free radicals in high efficiency. A broad range of substrate scope was examined and a number of 3,3-disubstituted oxindoles were synthesized in high yields.

A catalyst-controlled switchable reaction of ß-keto acids to silyl glyoxylates.

A catalyst-controlled switchable reaction of ß-keto acids to silyl glyoxylates was developed under mild conditions, providing two distinct products in good yields. Compared to decarboxylative addition-Brook rearrangement, the decarboxylative addition products could be controlled by using a simple bifunctional organocatalyst thiourea derivative instead of DABCO. This new reaction model of silyl glyoxylates offered a facile and alternative route to organosilicon compounds.

Organocatalytic Asymmetric Vinylogous Aldol Reaction of Allyl Aryl Ketones to Silyl Glyoxylates.

A direct organocatalytic asymmetric vinylogous aldol reaction of allyl aryl ketones to silyl glyoxylates has been developed through the bifunctional catalyst, giving the α-hydroxysilanes with excellent enantioselectivity (up to 95% ee) and in high yields (up to 96%). The success of this catalytic methodology offers an opportunity to tackle the problems in the nucleophilic addition to acylsilanes. To activate both allyl aryl ketones and acylsilanes, the utilized bifunctional catalyst was an ideal organocatalyst in this unprecedented transformation.

Organocatalyzed Direct Aldol Reaction of Silyl Glyoxylates for the Synthesis of α-Hydroxysilanes.

A novel organocatalyzed direct aldol reaction of aldehydes to silyl glyoxylates is disclosed. This method provides an efficient route to α-hydroxysilanes with excellent enantioselectivities (up to 99% ee) and high diastereoselectivities (up to >20:1 dr). In the new activation model of silyl glyoxylates, the hydrogen bond is critical to the reaction. A carbonyl group directly attached to silicon in acylsilanes could be activated by coordination to the proton of hydroxyl and carboxylic acid via a hydrogen bond. Moreover, commercially available cis-l-4-hydroxyproline is an ideal organocatalyst for activating both aldehydes and acylsilanes.

Organobase-catalyzed [1,2]-Brook rearrangement of silyl glyoxylates.

A highly efficient [1,2]-Brook rearrangement of silyl glyoxylates has been developed using DBU as the organobase-catalyst. This [1,2]-Brook rearrangement is applicable to a number of thiols and secondary phosphine oxides containing acidic protons. These nucleophiles afford the corresponding Brook products in high yields. Using this methodology, a formal synthesis of anti-HIV drug compound lamivudine was realized.

Insights into the asymmetric heterogeneous catalysis in porous organic polymers: constructing a TADDOL-embedded chiral catalyst for studying the structure-activity relationship.

Construction of porous organic polymers (POPs) as asymmetric catalysts remains as an important but challenging task. Herein, we exploit the "bottom-up" strategy to facilely synthesize an α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based chiral porous polymer (TADDOL-CPP) for highly efficient asymmetric catalysis. Constructed through the covalent linkages among the three-dimensional rigid monomers, TADDOL-CPP possesses hierarchical porous structure, high Brunauer-Emmett-Teller (BET) surface area, together with abundant and uniformly-distributed chiral sites. In the presence of [Ti(OiPr)4], TADDOL-CPP acts as a highly efficient and recyclable catalyst in the asymmetric addition of diethylzinc (Et2Zn) to aromatic aldehydes. Based on the direct observation of the key intermediates, the reaction mechanism has been revealed by solid-state (13)C magic-angle spinning (MAS) NMR spectroscopy. In combination with the catalytic testing results, characterization on the working catalyst provides further information for understanding the structure-activity relationship. We suggest that the catalytic activity of TADDOL-CPP is largely affected by the structural rigidity, cooperative catalysis, local chiral environment, and hierarchical porous framework. We expect that the information obtained herein will benefit to the designed synthesis of robust POP catalysts toward practical applications.

A concise synthesis of L-pyrrolysine.

Organocatalysis: A concise synthesis of L-pyrrolysine has been accomplished in six steps from simple starting materials. The facile synthetic strategy relies on an organocatalytic Michael addition, an efficient amide coupling, and a challenging method for the imine-bond construction.