Copper-Catalyzed Aza-Benzyl Transfer Michael Addition via C-C Bond Cleavage.

A non-noble Cu-catalyzed transfer aza-benzyl Michael addition via the C-C bond cleavage of aza-benzyl alcohols has been disclosed. The unstrained C(sp3)-C(sp3) bond of an alcohol was selectively cleaved. This aza-benzyl transfer strategy provides a selective and environmentally benign approach for the C-alkylation of α,ß-unsaturated carbonyl compounds that employs readily available alcohols as carbon nucleophiles and is characterized by a wide range of substrates and good to excellent yields.

Alkynyl Borrowing: Silver-Catalyzed Amination of Secondary Propargylic Alcohols via C(sp3)-C(sp) Bond Cleavage.

The silver-catalyzed alkynyl borrowing amination of secondary propargyl alcohols via C(sp3)-C(sp) bond cleavage has been developed. This new strategy was based on the ß-alkynyl elimination of propargyl alcohols and alkynyl as the borrowing subject. This alkynyl borrowing amination featured high atom economy, wide functional group tolerance, and high efficiency.

Sulfonylation of Propargyl Alcohols with Sulfinamides for the Synthesis of Allenyl Sulfones.

A regio- and chemoselective sulfonylation of propargyl alcohols with sulfinamides in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) was developed. It provided straightforward and mild access to multi-substituted allenyl sulfones by using sulfinamides as the sulfonyl sources. This transformation was promoted by HFIP and did not require any catalysts or oxidants, which allowed for the successful conversion of various tertiary and secondary propargyl alcohols into allenyl sulfones in high yields.

Rhodium-Catalyzed Enantioconvergent Isomerization of Homoallylic and Bishomoallylic Secondary Alcohols.

We present herein an unprecedented enantioselective isomerization of homoallylic and bishomoallylic secondary alcohols, catalyzed by a commercially available rhodium-complex and a base. This catalytic redox-neutral process provides an effective access to chiral ketones in high efficiency and enantioselectivity, without the use of any stoichiometric reagent or generation of any waste. For the reaction of homoallylic alcohols, this system achieved not only a stereoconvergent access to chiral ketones bearing a ß-stereocenter (up to 95%, 86% ee) but also a concomitant oxidative kinetic resolution of the alcohol substrates (S > 20). In the case of bishomoallylic alcohols, an intriguing ligand-induced divergent reactivity was observed. A terminal-to-internal alkene isomerization promoted by Rh/L7 followed by redox isomerization using Rh/BINAP system produced chiral ketones bearing a γ-stereocenter with high yield and enantioselectivity. Mechanistic studies provided strong support for the redox-isomerization pathway with chain walking of the key alkyl-Rh intermediate.

Pd-Catalyzed Enantioselective [6+4] Cycloaddition of Vinyl Oxetanes with Azadienes to Access Ten-Membered Heterocycles.

We report herein the first enantioselective cycloaddition of vinyl oxetanes, the reaction of which with azadienes provided unprecedented access to ten-membered heterocycles through a [6+4] cycloaddition. By using a commercially available chiral Pd-SIPHOX catalyst, a wide range of benzofuran- as well as indole-fused heterocycles could be accessed in excellent yield and enantioselectivity. A unique Lewis acid induced fragmentation of these ten-membered heterocycles was also discovered.

Rhodium-Catalyzed Enantioselective Isomerization of Secondary Allylic Alcohols.

The first catalytic enantioselective isomerization of secondary allylic alcohols to access ketones with a α-tertiary stereocenter is presented. The racemic allylic alcohol substrates can be converted to the enantioenriched ketone products in a stereoconvergent fashion. The use of commercially available catalysts and mild reaction conditions makes this an attractive method in stereoselective synthesis.

Synthesis of 1,2,4,5-tetra-substituted benzenes via copper-catalyzed dimerization of γ,δ-unsaturated ketones.

An efficient cyclization for the synthesis of 1,2,4,5-tetra-substituted benzenes via copper catalyzed dimerization of γ,δ-unsaturated ketones has been described. This one-pot procedure employs the γ,δ-unsaturated ketones as the sole substrate with multiple C-C bond formation. This protocol features broad substrate scope and provides a facile and robust method to construct polysubstituted benzene derivatives under mild conditions.

Rhodium(III)-catalyzed three-component C(sp2)-H activation for the synthesis of amines.

Rhodium-catalyzed three-component C-H bond activation of aromatics with amides and aldehydes to synthesize amines was established. The addition of copper was found to be essential to ensure the high reactivity. The mechanistic studies indicated that key intermediates formed by the transmetallization between rhodium and copper could further promote the addition between 2-(pyridin-2-yl)-phenyl-metal species and imines. A series of densely substituted amines could be conveniently prepared by this one-step, three-component procedure from commercially available substrates via C-H bond activation with water as the only by-product.

Stereoselective construction of spiro(butyrolactonepyrrolidines) by highly efficient copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar cycloaddition.

Pyrrole into one: The catalytic asymmetric 1,3-dipolar cycloaddition of cyclic aldimino esters has been accomplished for the first time, enabling facile access to spiro(butyrolactonepyrrolidines) containing one spiro quaternary center and three tertiary stereogenic centers (see scheme). The catalytic system performs well with a broad range of substrates, furnishing synthetically useful adducts in high yields, with excellent diastereo- and enantioselectivities under mild conditions.

Ruthenium-Catalyzed 1,3-Aryl Redox Isomerization of Allylic Alcohols.

The isomerization of allylic alcohols to the corresponding carbonyl compounds is a well-established reaction in organic synthesis. However, 1,3-carbon migration is a quite challenging field, and thus transformation has remained elusive until now. Herein, we present the ruthenium-catalyzed intramolecular 1,3-aryl migrative isomerization, which provides a mild and environmentally friendly method to synthesize various ketones with high step- and atom-economy and broad substrate scope. Meanwhile, the Ru(III)-catalyzed C(sp3)-C(aryl) bond cleavage of unactivated allylic alcohols may serve as a heuristic paradigm for transition-metal-catalyzed C-C activation.

Silver-Catalyzed 1,3-Aza-Benzyl Migration of Allyl Alcohol.

Carbon migration of alkenyl alcohols has been recognized as an increasingly viable methodology in organic synthesis. Herein, we disclose a silver-catalyzed 1,3-aza-benzyl migration of allyl alcohols by utilizing chelation-assisted selective cleavage of an unstrained C(sp3)-C(sp3) bond. This approach provides an available, efficient, high atom-economic, and environmentally benign procedure, leading to alkylation products with broad substrate scopes and excellent yields. The migration proceeds via a one-pot, two-step process involving a free-state alkyl metal species.

1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP)-Assisted Catalyst-Free Sulfonation of Allylic Alcohols with Sulfinyl Amides.

A highly regioselective and catalyst-free sulfonation of allylic alcohols with sulfinyl amides has been realized. Such a mix-and-go procedure provides a convenient approach to synthetically various allylic sulfones under mild reaction conditions. Furthermore, this novel reaction shows ample substrate scope and outstanding functional group tolerance and could also be scaled-up. Meanwhile, it is the first example that sulfinyl amides act as a powerful sulfur nucleophile in the reactions. 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) as a solvent plays a critical role in allylic sulfonation.

Catalytic asymmetric 1,3-dipolar cycloaddition of N-unprotected 2-oxoindolin-3-ylidene derivatives and azomethine ylides for the construction of spirooxindole-pyrrolidines.

Asymmetric 1,3-dipolar cycloaddition of N-unprotected 2-oxoindolin-3-ylidene with azomethine ylides for the construction of spirooxindole-pyrrolidines bearing four contiguous stereogenic centers has been achieved with AgOAc/TF-BiphamPhos complexes for the first time. This catalytic system performance well over a broad scope of substrates, providing the synthetically useful adducts in high yields and excellent diastereoselectivities and moderate enantioselectivities.

Cyano-borrowing: titanium-catalyzed direct amination of cyanohydrins with amines and enantioselective examples.

The direct amination of cyanohydrins with amines via a catalytic cyano-borrowing reaction was developed. The transformation features broad substrate scope, excellent functional group compatibility, and very mild and simple operations. Moreover, a titanium catalyst supported by quinine and (S)-BINOL ligands enabled an asymmetric cyano-borrowing reaction with moderate to high enantioselectivity.

Cyano-borrowing reaction: nickel-catalyzed direct conversion of cyanohydrins and aldehydes/ketones to ß-cyano ketone.

A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented "cyano-borrowing reaction" has been developed. Cleavage of the C-CN bond of cyanohydrins followed by aldol condensation and conjugate addition of cyanide to α,ß-unsaturated ketones proceeded to deliver a range of racemic ß-cyano ketones with good to high yields. The practical procedure with the use of a commercial and less-toxic CN source bodes well for wide application of this protocol.

Titanium-Catalyzed Cyano-Borrowing Reaction for the Direct Amination of Cyanohydrins with Ammonia.

α-Aminonitrile was an important building block in natural products and key intermedia in organic chemistry. Herein, the direct amination of cyanohydrins with the partner of ammonia to synthesis N-unprotected α-aminonitriles is developed. The reaction proceeds via titanium-catalyzed cyano-borrowing reaction, which features high atom economy and simple operation. A broad range of ketone or aldehyde cyanohydrins was tolerated with ammonia, and the N-unprotected α-aminonitriles were synthesis with moderate to high yields under mild reaction conditions.

Divergent reactivities in fluoronation of allylic alcohols: synthesis of Z-fluoroalkenes via carbon-carbon bond cleavage.

An unconventional cleavage of an unstrained carbon-carbon bond in allylic alcohols can be induced by the use of N-fluorobenzenesulfonimide (NFSI) under catalyst-free conditions. By using this simple procedure, a wide range of functionalized Z-fluoroalkenes can be accessed in high yield and selectivity from cyclic and acyclic allylic alcohols.

Highly enantioselective synthesis of chiral cyclic allylic amines via Rh-catalyzed asymmetric hydrogenation.

Highly regioselective and enantioselective asymmetric hydrogenation of cyclic dienamides catalyzed by an Rh-DuanPhos complex has been developed, which provides a readily accessible method for the synthesis of chiral cyclic allylic amines in excellent enantioselectivities (up to 99% ee). The products are valuable chiral building blocks and could be easily transformed to multisubstituted cyclohexane derivatives.

Catalytic enantioselective desymmetrization of meso cyclic anhydrides via iridium-catalyzed hydrogenation.

A novel method to desymmetrize meso-anhydrides into lactones via asymmetric hydrogenation catalyzed by the Ir-C3*-TunePhos complex has been developed. Various chiral lactones were synthesized with full conversion and excellent enantioselectivity under high reaction temperature.