α‐Substituted β‐acetyl amides could undergo C C bond cleavage to form α‐keto amides when treated with copper(II) chloride (CuCl2) and boron trifluoride diethyl etherate (BF3⋅OEt2) under an oxygen atmosphere. The yield can be increased by the addition of tert‐butyl hydroperoxide which alone can also effect the reaction. The reaction provides a new protocol for the synthesis of α‐keto amides.
A new copper‐mediated synthesis of α‐sulfonylethanone oximes from styrenes, sodium arylsulfinates and tert‐butyl nitrite (t‐BuONO; TBN) is presented. This intermolecular three‐component method enables the one‐step formation of C N and C S bonds under mild conditions, and represents a new, straightforward approach to α‐sulfonylethanone oximes.
A mild and efficient transition metal‐free approach has been developed for the synthesis of highly substituted chiral morpholines from alkenols by amino acid‐derived iodine(III) reagents via a 6‐exo‐trig cyclization. The key features of this work include the formation of three chiral centers with a high diastereomeric ratio, broad functional group compatibility, and atom/time economic methodology.
Two transformations initiated by photoinduced one‐electron transfer to α‐bromo ketones have been demonstrated. Hantzsch esters donate one electron to α‐bromo ketones under photoirradiation, promoting reductive debromination. Subsequent reactions of the resulting radical species of the ketones with molecular oxygen and Hantzsch esters lead to α‐hydroxylation or debromination, respectively. The relative dominance of the two pathways depends profoundly on the reaction conditions, including solvent, O2 levels, and the concentration of the Hantzsch esters. The synthetic protocols feature advantages because they require the environmentally benign sources, molecular oxygen and visible light.
The rhodium(I)‐catalyzed cycloisomerization of enynes with tethered (S)‐2‐methyl‐2‐propanesulfinyl imine affords 5‐ or 6‐membered cyclic compounds containing exocyclic 1,3‐diene moieties in a stereoselective manner. The reaction proceeds through β‐hydride elimination of a 7‐membered azarhodacycle intermediate, which is generated from three unsaturated bonds (i.e., alkene, alkyne, and CN bonds) and an Rh(I) complex. The resultant cyclic compounds could be reacted with various dienophiles to afford spiroamides as single isomers through the Diels–Alder reaction.
Recent progress in asymmetric organocatalysis has led to the development of several asymmetric transformations that employ various substrates. Among these, cyanoacetates have emerged as excellent nucleophiles in conjugate addition, alkylation, Mannich and α‐heterofunctionalization reactions. In this review we discuss the enantioselective functionalization of 2‐cyanoacetates through organocatalytic reactions.
The highly catalytic asymmetric α‐hydroxylation of β‐indanone esters and β‐indanone amides using peroxide as the oxidant was realized with a new C‐2′ substituted Cinchona alkaloid derivatives. The two enantiomers of α‐hydroxy‐β‐indanone esters could be obtained by simply changing the oxidant. This protocol allows a convenient access to the corresponding α‐hydroxy‐β‐indanone esters and α‐hydroxy‐β‐indanone amides with up to 99% yield and 98% ee.
The iron(III) chloride‐multicatalyzed dioxygenation of enamides with TEMPO in the presence of alcohols has been developed. This multicomponent domino process affords efficient new strategies for the synthesis of α‐oxy‐N‐acylhemiaminals or α‐oxyimides in good to excellent yields under mild conditions.
A highly effective aldol cyclization of α‐isothiocyanato imide to both β,γ‐unsaturated α‐keto esters and aryl‐substituted α‐keto esters has been developed. A chiral N,N′‐dioxide–yttrium triflate complex was used as the catalyst. A series of cyclic thiocarbamates bearing chiral quaternary stereocenters was synthesized in good to high yields, excellent diastereo‐ (up to 25:1 dr) and enantioselectivities (up to 99 % ee). In addition, the reaction could be carried out on a gram‐scale, and other functionalized derivatives are also conveniently transformed. Interestingly, a discrepancy of diastereoselection was observed between the reactions of β,γ‐unsaturated α‐keto esters and aryl‐substituted α‐keto esters. Moreover, a substrate dependency of non‐linear effects was observed in this reaction. On the basis of the experimental results and the absolute configuration of the products, possible catalytic models have been proposed to explain the origin of the asymmetric process.
A straightforward approach for the chemodivergent synthesis of quinolines is described through site‐selective coupling of ortho‐aminoaryl ketones with α‐enolic dithioesters (DTEs) under solvent‐free conditions. The operationally and user‐simple one‐pot methodology is based on the trifunctional nature of DTEs. Both the carbonyl and the thiocarbonyl moiety in α‐enolic dithioesters were employed for the efficient construction of three differently substituted quinolines in a chemoselective manner simply by variation of an easy to handle acid catalyst.
The first example of a nucleopalladation‐triggered carbene insertion reaction for the synthesis of C‐3 alkylated indole derivatives from ortho‐alkynyltrifluoroacetanilides and α‐diazoacetates is presented; it involves a palladium catalyst and a weak base in the open air. Yields range from 49–88% with excellent functional group tolerance. The reaction proceeds through intramolecular aminopalladation of alkynes followed by carbene insertion. Migratory insertion of the carbene into the σ‐indolylpalladium intermediate was favored over N H insertion.
Chiral primary amine‐catalyzed asymmetric C H functionalization has been achieved. In this process, enantiotopic Csp3 H functionalization at the α‐position to the nitrogen atom of 4‐[ortho‐(dialkylamino)phenyl]but‐3‐en‐2‐one is activated by chiral 9‐amino(9‐deoxy)‐epi‐quinine to afford tetrahydroquinine derivatives with high enantioselectivities (up to 97% ee).
The amination of racemic α‐chiral aldehydes, 2‐phenylpropanal derivatives, was investigated employing ω‐transaminases. By medium and substrate engineering the optical purity of the resulting β‐chiral chiral amine could be enhanced to reach optical purities up to 99% ee. Using enantiocomplementary ω‐transaminases allowed us to access the (R)‐ as well as the (S)‐enantiomer in most cases. It is important to note that the stereopreference of the ω‐transaminases found for α‐chiral aldehydes did not correlate with the stereopreference previously observed for the amination of methyl ketones. In one case the stereopreference switched even upon exchanging a methyl substituent to a methoxy group.
A novel, atom efficient, orthogonal tandem catalysis was developed yielding acyloin products (α‐hydroxy ketones) directly from olefins under hydroformylation conditions. The combination of a metal‐catalysed hydroformylation and an organocatalysed acyloin reaction provides three atom efficient C C bond formations to linear, multifunctional molecules via linkage of the intermediate n‐aldehydes. Additionally, the rhodium catalyst system gives a high n/bra ratio with an exclusive conversion of the terminal double bond in the hydroformylation and the n‐aldehydes are converted selectively to their acyloins.
A palladium(II)/copper oxide (Cu2O)‐catalyzed one‐pot decarboxylative and direct C H arylation of 2‐picolinic acid with aryl bromides has been developed. Various aryl bromides have been shown to be efficient coupling partners in the presence of dimethyl sulfate, furnishing symmetrical 2,6‐diarylpyridines in moderate to good yields.
