SmI2-mediated intermolecular addition-elimination of piperidine and pyrrolidine N-α-radicals with arylacetylene sulfones.

An efficient approach to access α-arylacetylene-substituted pyrrolidine and piperidine derivatives has been developed through a samarium diiodide-mediated addition-elimination process of pyrrolidine and piperidine N-α-radicals with arylacetylene sulfones.

AgNTf2-Catalyzed Regioselective C-H Alkenylation of N,N-Dialkylanilines with Ynamides.

Regioselective C-H alkenylation of N,N-dialkylanilines with ynamides was developed using AgNTf2 as a catalyst. This approach represents a facile hydroarylation of ynamides, allowing for the introduction of an alkenyl group exclusively at the para position of aniline derivatives. As a result, a series of 4-alkenyl N,N-dialkylanilines were synthesized with excellent regioselectivities.

A One-Pot Approach to 2-Substituted-2-(Dimethoxyphosphoryl)-Pyrrolidines from Substituted tert-Butyl 4-Oxobutylcarbamates and Trimethyl Phosphite.

A novel approach to 2-substituted-2-(dimethoxyphosphoryl)-pyrrolidines 7a-7o and 9a-9r has been developed, which features a TMSOTf-mediated one-pot intramolecular cyclization and phosphonylation of substituted tert-butyl 4-oxobutylcarbamates. The major advantages of this method include simple operation under mild reaction conditions, the use of cheap Lewis acid, and good to excellent yields with high diastereoselectivities (dr up to 99:1).

Cu(OTf)2 catalyzed Ugi-type reaction of N,O-acetals with isocyanides for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides.

The Cu(OTf)2 catalyzed Ugi-type reactions of N,O-acetals with isocyanides have been described for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides. 4-Hydroxy-5-substituted-prolinamides can be obtained in high diastereoselectivities (2,4-cis/trans > 19 : 1) and a stereoselective model was proposed for 2,4-cis selectivity. Moreover, 4-F-VH 032, a novel analog of the VHL ligand, was conveniently obtained by utilizing the present method.

Nickel-Catalyzed Regioselective Hydroamination of Ynamides with Secondary Amines.

The first Ni(OTf)2-catalyzed hydroamination of ynamides 2 was developed by reacting with secondary amines (1 and 4). This protocol features excellent regioselectivity, a broad substrate scope of secondary aryl amines, and good functional group tolerance for ynamides. Using this method, a variety of substituted ethene-1,1-diamine compounds were prepared in moderate to excellent yields with high regioselectivities.

Synthesis of Functionalized Bicyclo[2.2.2]octan-2-ones Skeleton via Tandem Process of Amino Acid Involved Formal [4 + 2] and Decarboxylative-Mannich Sequence.

An efficient approach to a functionalized bicyclo[2.2.2]octan-2-one scaffold has been developed through a one-pot cascade process including amino acid involved successive Michael addition and decarboxylative-Mannich sequence. Starting from α,ß-unsaturated ketones and amino acids, a series of desired products 7a-7m and 8a-8o were obtained with moderate yields. In addition, the tandem process was reasonably explained by the results of DFT calculations.

Sc(OTf)3-catalyzed [3 + 2]-cycloaddition of nitrones with ynones.

An efficient approach to access functionalized (2,3-dihydroisoxazol-4-yl) ketones has been developed by reacting nitrones 4 with ynones 7 or terminal ynones 10 in a one-pot fashion. The reaction went through a formal Sc(OTf)3-catalyzed [3 + 2]-cycloaddition process to generate a number of functionalized (2,3-dihydroisoxazol-4-yl) ketones 11aa-11aw, 11ba-11la and 12aa-12ae in moderate to good yields.

Synthesis of a 3,4-Dihydro-1,3-oxazin-2-ones Skeleton via an Intermolecular [4 + 2] Process of N-Acyliminium Ions with Ynamides/Terminal Alkynes.

An approach to access functionalized 3,4-dihydro-1,3-oxazin-2-ones has been developed by reacting semicyclic N,O-acetals 5 and 6 with ynamides 7 or terminal alkynes 8 in a one-pot fashion. The reaction went through a formal [4 + 2] cycloaddition process to generate a number of functionalized 3,4-dihydro-1,3-oxazin-2-ones 9a-9ak and 10a-10bc in yields of 34-97%. In addition, the utility of this transformation was demonstrated by the synthesis of (±)-sedamine 13.

Synthesis of 1-benzylisoindoline and 1-benzyl-tetrahydroisoquinoline through nucleophilic addition of organozinc reagents to N,O-acetals.

A new approach to access 1-benzylisoindoline and 1-benzyl-tetrahydroisoquinoline has been developed through nucleophilic addition of organozinc reagents to N,O-acetals. A number of substituted organozinc reagents were amenable for this transformation, and the desired products were obtained with excellent yields. Moreover, Sc(OTf)3 proved to be an effective catalyst for the formation of 1-benzylisoindoline and 1-benzyl-tetrahydroisoquinoline using such nucleophilic addition.

Gold-Catalyzed Addition-N-Boc Cleavage-Cyclization of N,O-Acetal with Ynamides for Construction of 6-(tert-Butyldimethylsilyl)oxy-tetrahydropyrrolo[1,2-c][1,3]oxazin-1-ones.

A highly efficient gold-catalyzed approach between N,O-acetals and ynamides for the construction of 6-(tert-butyldimethylsilyl)oxy-tetrahydropyrrolo[1,2-c][1,3]oxazin-1-ones was developed. This reaction tolerated a wide range of substituted N,O-acetals and TsN-substituted ynamides, leading to novel heterocycles in moderate to good yields and with excellent diastereoselectivities (dr > 99:1).

Synthesis of Amide Enol Carbamates and Carbonates through Cu(OTf)2-Catalyzed Reactions of Ynamides with t-Butyl Carbamates/Carbonates.

A highly regioselective approach to access amide enol carbamates and carbonates 5a-5c', 7a-7h, and 9 was developed through Cu(OTf)2-catalyzed reactions of ynamides 4 with t-butyl carbamates 2 and 8 and t-butyl carbonates 6. Moreover, this strategy was successfully applied to generate amide enol carbamates 11a-11s and 14a-14f from imides 10 and 13 with ynamides through an N-Boc cleavage-addition ring-opening process. A range of substituents was amenable to this transformation, and the desired amide enol carbamates and carbonates were obtained in moderate to good yields.

Divergent synthesis of N-heterocyclic 1,6-enynes through a zinc-catalyzed decarboxylative A3 reaction.

A zinc-catalyzed decarboxylative A3 reaction of cyclic amino acids, α,ß-unsaturated aldehydes and terminal alkynes has been developed. A series of functionalized N-heterocyclic 1,6-enynes have been successfully obtained with excellent regioselectivities through this novel approach. In addition, the utility of this straightforward process is demonstrated by the preparation of a polycyclic nitrogen-containing heterocyclic compound.

Approach to Tertiary-Type ß-Hydroxyl Carboxamides Through Sc(OTf)3-Catalyzed Addition of Ynamides and Ketones.

An efficient approach to access functionalized tertiary-type ß-hydroxyl carboxamides has been developed through Sc(OTf)3-catalyzed addition of ynamides and substituted ketones. Water was found to be an important reaction substrate, and the solvent was not needed in this process. A broad range of substituted ynamides and ketones was well applicable to the reaction with excellent chemical selectivities. Moreover, several chiral ß-hydroxyl carboxamides 3j-3r were prepared with excellent regioselectivities and outstanding diastereoselectivities.

Synthesis of 1,4- and 1,5-Amino Alcohols via Nucleophilic Addition of Semicyclic N,O-Acetal with Organozinc Reagents.

An efficient approach to access functionalized 1,4- and 1,5-amino alcohols has been developed through the nucleophilic addition of semicyclic N,O-acetal with organozinc reagents. A number of substituted benzyl zinc reagents (including nitrile and ester substituted) could react with semicyclic N,O-acetals 1 and 2, affording the desired products 3a-3p and 4a-4o in good to excellent yields.

Stereoselective Synthesis of Pyrido- and Pyrrolo[1,2- c][1,3]oxazin-1-ones via a Nucleophilic Addition-Cyclization Process of N, O-Acetal with Ynamides.

An efficient asymmetric approach to access functionalized pyrido- and pyrrolo[1,2- c][1,3]oxazin-1-ones has been developed through a nucleophilic addition-cyclization process of N, O-acetal with ynamides. A number of substituted ynamides 8a-8o and 3-silyloxypyrrolidine or piperidine N, O-acetals 6a, 7 were amenable to this transformation, and the desired products 9a-9o, 10a-10m were obtained with excellent regioselectivities and outstanding diastereoselectivities. Moreover, chiral ynamides 14a-14f could also experience this addition-cyclization process to afford products 15a-15f in excellent yields.

Zinc-Mediated Decarboxylative Alkylation of Gem-difluoroalkenes.

An efficient and mild zinc-mediated decarboxylative alkylation of gem-difluoroalkenes with N-hydroxyphthalimide (NHP) esters, to give monofluoroalkenes in moderate to excellent yields with high Z-selectivity is reported. The reaction tolerates a broad range of functional groups and can be easily scaled up, which thus may pave the way for its further applications in medicinal chemistry and materials science.

Approach to Chiral 1-Substituted Isoquinolone and 3-Substituted Isoindolin-1-one by Addition-Cyclization Process.

An approach to access 1-substituted isoquinolones has been developed through the addition-cyclization of imines with Grignard reagents in the presence of 2,2'-dipyridyl. A number of substituted aromatic magnesium reagents were amenable to this process, and the desired products were obtained with excellent yields and outstanding diastereoselectivities ( dr > 99:1). The utility of this convenient approach is demonstrated by the formal synthesis of ( S)-cryptostyline II. Moreover, N-methylmorpholine (NMM) was found to be an effective additive for the formation of 3-substituted isoindolin-1-ones using one-pot addition-cyclization-deprotection of imine with Grignard reagents.

Regio- and Stereoselective Cascades via Aldol Condensation and 1,3-Dipolar Cycloaddition for Construction of Functional Pyrrolizidine Derivatives.

An efficient and step-economical approach to access functionalized pyrrolizidine derivatives by a one-pot tandem sequence, including an aldol condensation and subsequent 1,3-dipolar cycloaddition process, has been developed, starting from acetone, aldehyde, and proline. A number of substituted aromatic aldehydes were amenable to this transformation, and the desired products, racemic 7a-7w and chiral 9a-9m, were obtained with excellent regioselectivities and outstanding diastereoselectivities. Moreover, in situ NMR studies revealed MgSO4 could effectively promote the aldol condensation pathway in this tandem process.

Asymmetric Synthesis of Rupestonic Acid and Pechueloic Acid.

In this report, the originally proposed rupestonic acid (5) and pechueloic acid (3) were efficiently synthesized. The chiral lactone 13, recycled from the degradation of saponin glycosides, was utilized to prepare the key chiral fragment 11. During the exploration of this convergent assembly strategy, the ring-closing metathesis (RCM), SmI2-prompted intermolecular addition, and [2,3]-Wittig rearrangement proved to be effective transformations for the synthesis of subunits.