N-sulfonyl Ketimines Research Articles

Asymmetric Hydrosilylations of N-Sulfonyl Ketimines and Vicinal Diimines with Chiral Boranes

Asymmetric Hydrosilylations of N-Sulfonyl Ketimines and Vicinal Diimines with Chiral Boranes

Water enables diastereodivergency in bispidine-based chiral amine-catalyzed asymmetric Mannich reaction of cyclic N-sulfonyl ketimines with ketones.

Tuning diastereoselectivity is a great challenge in asymmetric catalysis for the inherent stereochemical bias of the substrates. Here, we report a diastereodivergent asymmetric Mannich reaction of cyclic N-sulfonyl ketimines with ketones catalyzed by a bispidine-based chiral amine catalyst, in which additional water switches the diastereoselectivity efficiently. Both chiral anti- and syn-benzosultams with potential anti-HIV-1 activity are obtained in excellent yields and good to excellent ee values. Control experiments and density functional theory (DFT) calculations were applied to study the diastereodivergent mechanism, which reveal that the diastereodivergent catalysis should be state-determined, and the water reverses the energies of states to realize the diastereodivergency. The findings are quite new and might inspire more diastereodivergent asymmetric synthesis.

Perovskite as Recyclable Photocatalyst for Annulation Reaction of N-Sulfonyl Ketimines.

A sustainable and cost-effective manner for the photocatalytic annulation reaction of N-sulfonyl ketimines with N-arylglycines to synthesize imidazolidine-fused sulfamidates (31 examples) by employing CsPbBr3 as a heterogeneous photocatalyst has been developed. The catalyst CsPbBr3 can be simply recovered from the reaction mixture and reused at least five times without an obvious reduction in its photocatalytic reactivity, exhibiting a high catalyst economic feature.

Iridium-Catalyzed Direct C–H Allylation of Ketimines

AbstractAromatic C–H allylation of N-sulfonyl ketimines with allyl alcohol or allyl phenyl ether as an allyl source is catalyzed by a cationic iridium complex. The presence of a catalytic amount of a pyridine derivative was found to be essential for the reaction. In contrast, direct C–H allylation of ketimines derived from benzophenone derivatives and p-methoxyaniline with allyl phenyl ether proceeded in the absence of pyridine derivatives.

Substrate-Controlled Domino Reaction of N-Sulfonyl Ketimines with 2-Aroyl-1-chlorocyclopropanecarboxylates: Access to Cyclopenta[c]chromenes and Benzo[f]cyclopenta[d][1,2]thiazepine Dioxides.

An unprecedented substrate-controlled annulation method for the synthesis of fascinating classes of angularly fused cyclopenta[c]chromenes and benzo[f]cyclopenta[d][1,2]thiazepine 5,5-dioxide derivatives in good to high chemical yields is reported. This Michael-initiated ring-expansion reaction would enable two C-C and one C-O or C-N bonds by a judicious choice of carbonucleophiles, either 4-alkyl or 3-alkyl-substituted N-sulfonyl ketimines, respectively, with a series of donor-acceptor cyclopropane scaffolds as 4C sources promoted by DBU. Moreover, this eco-friendly method is mild enough to protect different kinds of functionalities. Importantly, the prepared fused fulvene scaffolds were smoothly transformed into a special class of hexahydrocyclopenta[c]chromenes as single cis-cis-cis-cis diastereomers in excellent yields by a simple catalytic hydrogenation reaction.

Contrasting Carboannulation Involving δ-Acetoxy Allenoate as a Four-Carbon Synthon Using DABCO and DMAP: Access to Spiro-carbocyclic and m-Teraryl Scaffolds.

Spiro-annulation involving δ-acetoxy allenoate and alkyl benzoisothiazole dioxide (N-sulfonyl ketimine) triggered by DABCO/MeCO2H combination leads to an essentially single diastereomer via chemo- and regiospecific [4 + 2]-carboannulation and a new hydroxyl group is introduced. In contrast, DMAP-catalyzed benzannulation using the same reactants affords unsymmetrical m-teraryls via Mannich coupling, sequential proton transfers, and C-N bond cleavage. Here, δ-acetoxy allenoate serves as a 4C-synthon and the carboannulation is completely base dependent and mutually exclusive.

Palladium-catalyzed stereoselective (3 + 2) cycloaddition of vinylethylene carbonates with cyclic N-sulfonyl ketimines.

A diastereoselective (3 + 2) cycloaddition of N-sulfonyl ketimines with vinylethylene carbonates (VECs) in the presence of Pd2dba3·CHCl3 and PPh3 has been developed. The reaction of various substituted VECs and diverse cyclic N-sulfonyl ketimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to excellent yields with moderate to good diastereoselectivities. With the use of spiroketal-based diphosphine SKP as a chiral ligand, an asymmetric version of the current (3 + 2) cycloaddition was achieved, and chiral products were obtained in >99% ee in most cases.

Unmasking the reverse reactivity of cyclic N-sulfonyl ketimines: multifaceted applications in organic synthesis.

The chemistry related to the exploration of cyclic N-sulfonyl ketimines and their derivatives has attracted significant attention in the last few decades because of their intriguing structures and properties. They serve broadly as reactive synthons in various reactions to create a diverse set of synthetically and biologically attractive molecules. Furthermore, these moieties, which possess multiple heteroatoms (N, O and S), display or can enhance many biological activities. In the case of synthetic reactions, chemists mainly focus on the chemical manipulation of the highly reactive prochiral CN bond of N-sulfonyl ketimines. Besides their traditional role as electrophiles, N-sulfonyl ketimines possess α-Csp3-H protons, and thus behave as potential carbonucleophiles, where they can undergo several C-X (X = C, N and O) bond-forming reactions with different types of electrophiles under various conditions to form a wide range of fascinating asymmetric and non-asymmetric versions of fused heterocycles, carbocycles, spiro-fused skeletons, pyridines, pyrroles, etc. Herein, we highlight the recent examples from our research work and others covering the scope of cyclic N-sulfonyl ketimines as useful carbonucleophiles. In addition, the detailed mechanistic studies of the above-mentioned reactions are also presented.

Palladium/N,N'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Addition of Arylboronic Acids to Cyclic N-Sulfonyl Ketimines.

The combination of Pd(TFA)2 and an N,N'-disulfonyl bisimidazoline ligand shows high catalytic activity and excellent asymmetric induction in the addition of arylboronic acids to cyclic N-sulfonyl ketimines including benzo[d]isothiazole-1,1-dioxides, benzo[e][1,2,3]oxathiazine-2,2-dioxides, and 1,2,5-thiadiazole-1,1-dioxides, by which three types of chiral quaternary carbon-containing sultams with substantial substitution diversity were synthesized with high yields and excellent enantioselectivities (up to >99% ee). The current catalysis demonstrated a remarkable tolerance to oxygen and thus provided an operationally simple approach for constructing enantioenriched cyclic quaternary stereocenters.

Enantioselective Imino-Ene Reaction of N-Sulfonyl Ketimines with Silyl Enol Ethers: Access to Chiral Benzosultams.

A highly efficient asymmetric imino-ene reaction of cyclic ketimines with silyl enol ethers was developed. Various chiral benzosultam derivatives were obtained in excellent yields (up to 99%), enantioselectivities (up to 99% ee), and diastereoselectivities (up to >19:1 dr) by utilizing a Ni(BF4)2·6H2O/N,N'-dioxide complex as the catalyst. A possible transition state model was proposed to explain the stereoinduction. Furthermore, the synthetic utility of the protocol provided quick access to optically pure HIV-1 inhibitor.

The regioselective annulation of alkylidenecyclopropanes by Rh(iii)-catalyzed C-H/C-C activation to access spirocyclic benzosultams.

Functionalized benzosultams are an essential class of structural motif found in various biologically active molecules. The synthesis of spirocyclic benzosultams from N-sulfonyl ketimine and alkylidenecyclopropanes (ACPs) under the catalysis of Rh(iii) has been developed. This transformation enables the formation of two C-C bonds and a double bond with high E-selectivity through C-H and C-C bond activation. This reaction proceeded smoothly with excellent regioselectivity, high efficiency, and tolerance for various functional groups.

Synthesis of chiral α-substituted α-amino acid and amine derivatives through Ni-catalyzed asymmetric hydrogenation.

Highly efficient Ni-catalyzed asymmetric hydrogenation of cyclic N-sulfonyl ketimino esters was, for the first time, successfully developed, providing various chiral α-monosubstituted α-amino acid derivatives with excellent results (97-99% yields, 90 to >99% ee). Cyclic N-sulfonyl ketimines were also hydrogenated well to afford chiral amine derivatives with 98-99% yields and 97 to >99% ee. The gram-scale asymmetric hydrogenation was performed well with 85% yield and 99% ee using only 0.2 mol% catalyst.

Iridium-catalyzed direct C-H arylation of cyclic N-sulfonyl ketimines with arylsiloxanes at ambient temperature.

An iridium-catalyzed ortho-selective C-H arylation of cyclic N-sulfonyl ketimines has been achieved with environmentally benign aryl siloxanes. The reaction is highly efficient and proceeds at ambient temperature which is the key feature of the methodology considering the weak coordination nature of the substrate as well as the sluggish reactivity of siloxanes. A wide array of pharmaceutically relevant novel biaryls has been synthesized under operationally simple conditions.

NH4OAc-Promoted Domino Route to Hydroxyarylated Unsymmetrical Pyridines under Neat Conditions.

A new metal-, oxidant-, and solvent-free ecofriendly domino method has been established for modular synthesis of a diverse range of medicinally promising hydroxyarylated unsymmetrical pyridines in good to high chemical yields with an excellent regioselectivity. This domino process involves a range of N-sulfonyl ketimines as C,N-binucleophiles, enolizable ketones, and aromatic/heteroaromatic aldehydes using ammonium acetate as an ideal promoter under neat conditions, which creates two new C-C bonds and one C-N bond. Notably, the neutral reaction conditions are mild enough to tolerate a range of functionalities and cover a variety of substrates, thus bestowing a powerful avenue to access tri- and tetrasubstituted pyridines including carbo- and heterocyclic fused ones. Interestingly, a practical, scalable, and high-yielding synthesis of pyridylphenol derivatives was successfully accomplished by our unique method.

Synthesis of chiral quaternary fluorinated cyclic sulfamidates via palladium-catalyzed arylation with arylboronic acids

An enantioselective palladium-catalyzed arylation of fluorinated cyclic N-sulfonyl ketimines with arylboronic acids is described. This methodology provides an efficient and convenient route to chiral quaternary fluorinated cyclic sulfamidates in high yields with up to 99% ee.

Synthesis of Sultams and Cyclic N-Sulfonyl Ketimines via Iron-Catalyzed Intramolecular Aliphatic C-H Amidation.

Cyclic sulfonamides (sultams) play a unique role in drug discovery and synthetic chemistry. A direct synthesis of sultams by an intramolecular C(sp3)-H amidation reaction using an iron complex in situ derived from Fe(ClO4)2 and aminopyridine ligand is reported. This strategy features a readily available catalyst and tolerates a broad variety of substrates as demonstrated by 22 examples (up to 89% yield). A one-pot iron-catalyzed amidation/oxidation procedure for the synthesis of cyclic N-sulfonyl ketimines is also realized with up to 92% yield (eight examples). The synthetic utility of the method is validated by a gram-scale reaction and derivatization of the products to ring-fused sultams.

Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Sulfamidate Imines: Efficient Synthesis of Chiral Cyclic Sulfamidates.

SummaryChiral cyclic sulfamidates are useful building blocks to construct compounds, such as chiral amines, with important applications. Often these compounds can only be generated through expensive precious metal catalysts. Here, Ni(OAc)2/(S, S)-Ph-BPE-catalyzed highly efficient asymmetric hydrogenation of cyclic sulfamidate imines was successfully developed, affording various chiral cyclic sulfamidates with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess [ee]). This Ni-catalyzed asymmetric hydrogenation on a gram scale has been achieved with only 0.1 mol% catalyst loading in 99% yield with 93% ee. Other types of N-sulfonyl ketimines were also hydrogenated well to obtain the corresponding products with >99% conversion, 96%–97% yields, and 97%–>99% ee. In addition, this asymmetric methodology could produce other enantioenriched organic molecules, such as chiral β-fluoroamine, amino ether, and phenylglycinol. Moreover, a reasonable catalytic cycle was provided according to the deuterium-labeling studies, which could reveal a possible mechanism for this Ni-catalyzed asymmetric hydrogenation.

Asymmetric Organocatalyzed Reaction Sequence To Synthesize Chiral Bridged and Spiro-Bridged Benzofused Aminals via Divergent Pathways.

A highly efficient asymmetric organocatalysis-triggered reaction sequence is developed. 2-Hydroxy cinnamaldehydes and cyclic N-sulfonyl ketimines were both used as multisite substrates (more than two reactive sites) to access structurally diverse chiral bridged and spiro-bridged benzofused aminal derivatives, where an inseparable equilibrating mixture of isomers can be regioselectively converted into bridged benzofused aminals with different ring connectivities via divergent pathways. Several stereoselective transformations of the resulted bridged aminals are presented.

Diastereoselective Spirocyclization of Cyclic N-Sulfonyl Ketimines with Nitroalkenes via Iridium-Catalyzed Redox-Neutral Cascade Reaction.

An Ir(III)-catalyzed [3 + 2] annulation of weakly coordinating N-sulfonyl ketimines with challenging α, β-unsaturated nitro olefins has been achieved via redox-neutral C-H functionalization in the presence of a catalytic amount of silver hexafluoroantimonate. The generation of three consecutive stereogenic centers in a single step via direct C-H functionalization is the prime feature of this methodology. A wide array of pharmaceutically relevant nitro-substituted spirocyclic benzosultams was synthesized with good to excellent diastereoselectivity as well as in high yield starting from easily accessible substrates.

Chemoselective cyclization of N-sulfonyl ketimines with ethenesulfonyl fluorides: access to trans-cyclopropanes and fused-dihydropyrroles.

An interesting stereo- and chemoselective cyclization reaction of several N-sulfonyl ketimines as C/N-donors with a variety of α,β-unsaturated sulfonyl fluorides promoted by DBU is reported. This substrate-dependent selective C-C vs. C-N bond cyclization process leads to important classes of trans-cyclopropane and fused dihydropyrrole scaffolds in satisfactory yields with excellent diastereoselectivities (dr up to ≤99 : 1). High-yield single-stage synthesis of biologically interesting sulfamate-fused-pyrrole and 2-pyrrolyl phenol derivatives was successfully established.