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Here, we have successfully achieved the addition of difluoroacetate radicals to 2‐aryl‐3H‐indol‐3‐ones, enabling various difluoroalkylations of C2‐tetrasubstituted 2‐aryl indolin‐3‐ones in a highly efficient and economical manner. It is worth mentioning that these difluoroalkylation compounds can be easily transformed into various derivatives under mild reaction conditions. Control experiments suggest the involvement of ethyl difluoroacetate radical species in the reaction. [ABSTRACT FROM AUTHOR]

This study presents the synthesis of analogues of bioactive Amaryllidaceae alkaloids that contain a five‐membered ring C and a quaternary carbon centre. The synthesis was carried out in a divergent manner, starting from a common intermediate, keto aldehyde 1 a. This intermediate was obtained by oxidative cleavage of a carbocyclic ring present in the previously synthesised tetracyclic compounds. Subsequent closure of a new heterocyclic ring B using different methods led to products with structural cores found in naturally occurring alkaloids such as pretazettine, tazettine or macronine. In addition, an analogue of egonine was prepared from the same intermediate. Our approach thus provides access to multiple structural types of potentially bioactive molecules. [ABSTRACT FROM AUTHOR]

A practical method for the preparation of quaternary and tertiary allyl‐substituted heteroarenes by site‐selective couplings of heteroaryl nitriles and allylic nucleophiles is disclosed. Transformations utilize readily accessible stable reagents, proceed in the presence of a Lewis base activator, and undergo aryl‐C(sp3) quaternary and tertiary carbon formation with high γ‐selectivity (up to >98 : 2 γ : α). [ABSTRACT FROM AUTHOR]

Optical pharmaceutical important compounds which bring CF2H to mimic the role of –SH were synthesized through the asymmetric S‐Michael addition reaction in the presence of quinine–a derived squaramide catalyst. Various sulfhydryl compounds including Benzyl mercaptan, phenthiol, alkyl thiophenol, mercaptoacetate, methyl 3‐mercaptoacrylate, and 1,4‐dithiane‐2,5‐diol were tested. The broad substrate scope, good functional group tolerance, and easy derivatization make this synthesis method very attractive. [ABSTRACT FROM AUTHOR]

In this personal account, our recent developments on the asymmetric synthesis of a quaternary carbon stereogenic center by organocatalysis using a primary amino acid and its salt as a catalyst are described in three chapters: (1) conjugate addition to nitroalkenes and vinyl ketones, (2) nucleophilic addition to π‐allyl palladium complexes, and (3) nucleophilic substitution reactions with allyl and propargyl halides. By these methods, asymmetric α‐allylation of α‐branched aldehydes and ketones smoothly proceeded to give γ‐nitroaldehydes, ketoaldehydes, α‐allylated aldehydes, and α‐allylated β‐ketoesters possessing a quaternary carbon stereogenic center in good yields with high enantioselectivities. [ABSTRACT FROM AUTHOR]

A practical method for the efficient and enantioselective preparation of versatile ketones and aldehydes that contain an α‐quaternary stereocenter is described. Reactions utilize simple carboxylic acid or ester starting materials, a monodentate chiral phosphine, and afford a variety of aryl, alkenyl, alkynyl, and alkyl‐substituted ketone and aldehyde products in 25–94 % yield and 90 : 10 to >99 : 1 enantiomeric ratio. Reactions proceed by acyl substitution with in situ formed chiral allylic nucleophiles, and display selectivity and conversion dependence on a protic additive. The utility of the approach is demonstrated through several product transformations. [ABSTRACT FROM AUTHOR]

A Pd‐catalyzed decarboxylative approach for the construction of 2‐allyl‐2,2‐diarylacetaldehydes via dearomative umpolung strategy is reported. The reaction is applicable to a number of cyclic carbonates or allylic acetates featuring with different functional groups. These reactions could be performed in a gram‐scale but without loss of the reaction efficiency. The control experiments suggest that the reaction proceeds though a palladium catalyzed dearomative decarboxylation step followed by an umpolung nucleophilic attack. [ABSTRACT FROM AUTHOR]

Preparation of skipped dienes with a quaternary carbon center at the C‐3 position remains a synthetic challenge. We report here an iridium‐catalyzed formal addition of tertiary sp3 C−H bond to alkyne for the facile preparation of skipped dienes. The tertiary allylic C−H bond is cleaved regioselectively, at the site of which a new C−C bond is formed. Enantioselective construction of acyclic quaternary carbon stereocenters is also demonstrated. [ABSTRACT FROM AUTHOR]

Bicyclo[2.2.2]octane derivatives possessing a quaternary bridgehead carbon were synthesized with excellent diastereoselectivity in nearly optically pure form by diphenylprolinol silyl ether mediated domino Michael/Michael reaction of α,β‐unsaturated aldehyde and cyclohex‐2‐en‐1‐one bearing an electron‐withdrawing group at the 3‐position. Carbonitrile, alkoxycarbonyl, and sulfonyl substituents were successfully employed as a suitable electron‐withdrawing group at the 3‐position of cyclohex‐2‐en‐1‐one. [ABSTRACT FROM AUTHOR]

A Co‐catalyzed enantioselective desymmetric [2+2+2] cycloaddition for synthesis of pyridines with all‐carbon quaternary carbon centers has been developed. The regio‐ and enantioselectivities are controlled by the inherent nature of terminal alkynes and the substituents on the bisoxazolinephosphine ligands. Pyridines with 5‐substitutents could be obtained with >20:1 regioselectivity and up to 94 % ee when terminal alkyl, alkenyl or silyl alkynes and DTBM/Ph‐based NPN* ligand L6 were used. Terminal aryl alkynes and Ph/Bn‐based ligand L4 leads to formation of pyridines with 6‐substitutents in up to 99 % ee. [ABSTRACT FROM AUTHOR]

A novel semipinacol rearrangement using dibromocyclopropanes as sources of carbocations was developed. Heating dibromocyclopropanes bearing a 1-hydroxyalkyl group with silver perchlorate and 2,6-lutidine induced cleavage of the cyclopropane ring to form allyl cations, which underwent 1,2- shift of a substituent at the α-position of the hydroxy group to give β,γ-unsaturated carbonyl compounds having a quaternary carbon at the α-position. Because the products have convertible functional groups such as bromo, vinyl, and formyl groups, the method is expected to be applicable to the synthesis of various molecules. [ABSTRACT FROM AUTHOR]

Palladium‐catalyzed asymmetric [4+5] annulation of ortho‐quinone methides (o‐QMs) with substituted vinylethylene carbonates (VECs) is described for the first time, giving a novel enantioselective approach to chiral nine‐membered benzoheterocycles. Based on this designed [4+5] annulation, an unprecedented silica gel‐promoted tandem rearrangement reaction featuring a unique asymmetric aromatic Claisen rearrangement is explored at room temperature, offering a new method for asymmetric construction of all‐carbon quaternary stereocenters embedded in chiral functionalized homoallylic alcohols. [ABSTRACT FROM AUTHOR]

A TBAB‐mediated radical 5‐exo‐trig ipso‐cyclization of N‐aryl‐2‐arylbenzamide is described herein for the synthesis of spiro[cyclohexane‐1,1′‐isoindoline]‐2,5‐diene‐3′,4‐dione. The transformation proceeds regioselectively and provides the final products with high efficiency and a broad reaction scope. Mechanism studies show the use of TBAB as an additive is pivotal for the reaction. In the process, para‐bromination of N‐aryl group, 5‐exo‐tri ipso‐cyclization of N‐aryl‐2‐arylbenzamide nitrogen radical and sequential aromatization is involved. [ABSTRACT FROM AUTHOR]

Short gram‐scale asymmetric syntheses of asperazine, pestalazine A, and their unnatural congeners thereof, have been achieved in ≈10 steps by using readily accessible starting materials. The nickel‐catalyzed reductive coupling protocol was utilized as a key step for the direct construction of C3asp3−C7′sp2 bond furnishing the diaryl‐substituted quaternary carbon centers with remarkable steric hindrance. The streamlined access to this core structure of heterodimeric tryptophans under the mild reaction conditions, makes this strategy hold a great promise in the concise synthesis of other relevant oligomeric pyrroloindoline alkaloids with unique C3a−C7′ linkages. Highly efficient syntheses of bioactive alkaloids (+)‐asperazine and (+)‐pestalazine A were realized by means of Ni‐catalyzed reductive coupling between 7‐iodotryptophan and 3‐chlorocyclotryptophan derivatives. This key reaction secured the construction of C3a−C7′ bond and the associated sterically congested all‐carbon quaternary stereocenter in a single step. [ABSTRACT FROM AUTHOR]

From a single α‐silylated carbinol intermediate, easily accessible by carbometallation of cyclopropenes, various scaffolds featuring a quaternary carbon stereocenter could be obtained selectively. The selectivity towards these different products was achieved by either changing the experimental conditions or the nature of the organometallic species involved. From a single α‐silylated carbinol intermediate, easily accessible by carbometallation of cyclopropenes, various scaffolds featuring a quaternary carbon stereocenter could be obtained selectively. The selectivity towards these different products was achieved by either changing the experimental conditions or the nature of the organometallic species involved. [ABSTRACT FROM AUTHOR]

Efficient construction of quaternary carbon centers represents one of the most challenging goals in organic synthesis, and it has drawn tremendous research interest from organic chemist community. The past decade has witnessed a significant advancement of direct C−H functionalization, which delivers various synthetic tools for assembling structurally diversified architectures with the advantage of step‐ and atom‐economy, operational simplicity, and readily available substrates. In this Minireview, synthetic methods based on transition‐metal‐catalyzed C−H functionalization as efficient tools for the construction of quaternary carbon centers are summarized. C−H activation to make quaternary carbons: Transition‐metal‐catalyzed C−H activation offers an intriguing strategy for construction of quaternary carbon centers in a highly atom‐ and step‐economic manner with molecular complexity, which is highlighted in this Minireview. [ABSTRACT FROM AUTHOR]

The cationic AuI‐catalyzed cyclization of highly substituted enynes has been shown to provide cyclopentenones with up to two contiguous, all‐carbon atom quaternary centers in a diastereospecific process. In the more challenging examples in which two contiguous quaternary centers are formed during cyclization, the essential role of a ethoxycarbonyl group to control the reaction outcome has been demonstrated. The less challenging examples that lead to a single quaternary center in the ring require no activation by aryl or by electron withdrawing groups. [ABSTRACT FROM AUTHOR]

A rapid synthetic route toward (±)-Bakuchiol is presented in 29% overall yield. After the sole all-carbon quaternary carbon center is created via allylboration of 2-aryl acetaldehyde, a "Pot-Economy" approach including mesylation, elimination, and desilylation was realized in the presence of tBuOK under ambient temperature to provide (±)-Bakuchiol. [ABSTRACT FROM AUTHOR]

An assessment of biodegradability was carried out for fragrance substances containing quaternary carbons by using data obtained from Organisation for Economic Co-operation and Development (OECD) 301F screening tests for ready biodegradation and from Biowin and Catalogic prediction models. Despite an expected challenging profile, a relatively high percentage of common-use fragrance substances showed significant biodegradation under the stringent conditions applied in the OECD 301F test. Among 27 test compounds, 37% met the pass level criteria after 28 d, while another 26% indicated partial breakdown (≥20% biodegradation). For several compounds for which structural analogs were available, the authors found that structures that were rendered less water soluble by either the presence of an acetate ester or the absence of oxygen tended to degrade to a lesser extent compared to the primary alcohols or oxygenated counterparts under the test conditions applied. Difficulties were encountered when attempting to correlate experimental with in silico data. Whereas the Biowin model combinations currently recommended by regulatory agencies did not allow for a reliable discrimination between readily and nonbiodegradable compounds, only a comparably small proportion of the chemicals studied (30% and 63% depending on the model) fell within the applicability domain of Catalogic, a factor that critically reduced its predictive power. According to these results, currently neither Biowin nor Catalogic accurately reflects the potential for biodegradation of fragrance compounds containing quaternary carbons. Environ Toxicol Chem 2014;33:1005-1016. © 2014 SETAC [ABSTRACT FROM AUTHOR]

Based on the assumption that intramolecularly formed protic oxonium ylides could be trapped by electrophiles, transition-metal-catalyzed reactions of diazoesters bearing a primary hydroxy group with electron-deficient aldehydes and isatins were examined. Good to high chemo- and diastereoselectivities were achieved with reactions catalyzed by Cu(hfacac)2. The reactions were assumed to occur via tandem intramolecular protic oxonium ylide formation and subsequent aldol-type addition. They not only provided an efficient entry to 3-substituted 1,4-dioxan-2-one heterocycles with at least one quaternary carbon center but also provided experimental evidence for a stepwise pathway for the transition-metal-catalyzed intramolecular OH insertion of diazo compounds. [ABSTRACT FROM AUTHOR]

Cat. on a hot tin roof: Enantioselective catalytic Michael addition of α ‐ cyanoketones to acrylates under bifunctional organocatalysis was used to construct the unique arylic all ‐ carbon quaternary stereocenter, which is synthetically crucial in the chemical synthesis of optically pure cis ‐ aryl hydroindole alkaloids. The protocol offers an asymmetric route to (+) ‐ vittatine, (+) ‐ epi ‐ vittatine, and (+) ‐ buphanisine. [ABSTRACT FROM AUTHOR]

C−H Functionalization, as a focus of research interest in recent years, has delivered various synthetic tools for assembling structurally diversified architectures with the advantage of step‐ and atom‐economy, operational simplicity, and readily available substrates. While quaternary carbon centers are ubiquitous and yet synthetically challenging, in their Minireview Y. Li and S. Xu on page 16218 ff. summarize the recent synthetic methods based on transition‐metal‐catalyzed C−H functionalization for efficient construction of quaternary carbon centers. [ABSTRACT FROM AUTHOR]