Suzuki–Miyaura coupling of heteroaryls is an important method for the preparation of compound libraries for medicinal chemistry and materials research. Although many catalysts have been developed, none of them have been generally applicable to the coupling reactions of heteroaryl chlorides and tosylates at room temperature. We discovered that a catalyst combination of Pd(OAc)2 and XPhos (2‐dicyclohexylphosphanyl‐2′,4′,6′‐triisopropylbiphenyl) could efficiently catalyze these couplings. Besides the choice of catalyst, the use of hydroxide bases in an aqueous alcoholic solvent was essential for fast couplings. These conditions promoted fast release of active catalyst (XPhos)Pd0, and accelerated the transmetalation in the catalytic cycle. Most of the major families of heteroaryl chlorides (31 examples) and tosylates (17 examples) reached full conversion within minutes to hours at room temperature. The method could be easily scaled up for gram‐scale synthesis. Furthermore, we examined the relative reactivity of coupling partners in whole reactions. Electron‐rich heteroaryl chlorides and tosylates reacted more slowly than electron‐deficient ones, in the order of indole, pyrrole < furan, thiophene < pyridine and other six‐membered‐ring azines. For heteroarylboronic acids, the reactivity ranking was reversed: indole, pyrrole > furan, thiophene > pyridine. Similarly, electron‐deficient arylboronic acids were less reactive than electron‐neutral and electron‐rich ones. The reactivity trends from this study can help to choose appropriate coupling partners for Suzuki reactions.

The one-carbon homologation of carbonyl compounds using diazo compounds is a frequently encountered synthetic objective. [1] Several related reactions have been developed and are known as the Arndt-Eistert reaction, [2] Buchner-Curtius-Schlotterbeck reaction, [3] Tiffeneau-Demjanov rearrangement, [4] and Roskamp-Feng reaction. [5] Among these reactions, Lewis acid catalyzed homologation of aldehydes or ketones with diazo compounds results in a carbon-chain extension or ring expansion at a carbonyl group, thus producing a synthetically useful carbonyl-containing backbone (Scheme 1). [6,7] Remarkably, the reactions found successful applications in natural product synthesis in recent years. [8] Intriguingly, a catalytic asymmetric variant of this transformation by using a-substituted a-diazo compounds will incorporate a chiral tertiary (for aldehydes) or quaternary (for ketones) carbon center [9] at the position adjacent to the carbonyl group (Scheme 1). Recently, innovative studies by several groups have been extended to the asymmetric reaction of aldehydes and cyclic carbonyl compounds. Asymmetric homologation of aldehydes with a-alkyl-a-diazo com-pounds were documented by Maruoka and co-workers, [10] ourselves, [11] and Ryu and co-workers. [12] Stereoselective construction of seven-membered rings from cyclohexanones was accomplished by the group of Maruoka by using a chiral aluminum complex of a binol derivative. [13] An asymmetric ring expansion of cycloalkanones with terminal diazoalkanes was reported by Kingsbury and co-workers by using chiral scandium complexes of oxazoline ligands. [14] We realized the corresponding ring-expansion reaction of isatins. [11c] Nevertheless, daunting challenges remain in the asymmetric carbonchain extention of acyclic ketones. Compared with the asymmetric homologation of cycloalkanones, the control of the enantioselectivity and regioselectivity of acyclic ketones (Scheme 1, path a) is more complex without the ring system. Additionally, acyclic ketones receive more steric hindrance than the relatively bare carbonyl group on a cyclic ring, which reduces the reactivity. Otherwise, the formation of epoxides from acyclic ketones is highly competitive relative to aldehydes and cyclic ketones. [1a,b] Continued improvement of asymmetric homologation of ketones achieved by new Lewis acid catalysts under mild reaction conditions is significantly desired. We report herein a breakthrough by using chiral N,N'-dioxide-yttrium(III) complexes. Asymmetric homologation of a-ketoesters with a-alkyl-a-diazoesters was achieved, thus generating enantiomeric enriched succinate derivatives with chiral all-carbon quaternary centers.After preliminary screening, we chose the a-ketoester 1 a and a-methyl-a-diazoester 2 a as the model substrates for catalysis using chiral N,N'-dioxide/metal complexes [15] (Table 1). Surprisingly, the catalyst L1/Sc(OTf) 3 , which was efficient in our previous study, [11] could not promote the reaction of the a-ketoester (entry 1). The complexes of Ni(OTf) 2 and Zn(OTf) ...

The first enantioselective conjugate addition of silyl ketene imines to in situ generated indol-2-ones was performed in the presence of a chiral N,N'-dioxide/Ni catalyst. This method provides efficient access to chiral β-alkyl nitriles bearing congested vicinal all-carbon quaternary stereocenters in up to 90 % yield with 23:1 d.r. and 98 % ee. The products enable facile transformations to chiral pyrroloindoline frameworks and spirocyclohexane oxindole derivatives. A possible transition state was also proposed to explain the origin of the asymmetric induction.

Five glutarimide alkaloids cordiarimide A (5), cordiarimide B (6), crotonimide A (3), crotonimide B (4), and julocrotine (2) have been synthesized starting from Boc-L-glutamine (7). The benzylic alcohol chiral centre of cordiarimides B (6) has been established in 6 : 1 diastereoselectivity by catalytic asymmetric hydrogenation using Zhou's catalytic system Pd(CF(3)CO(2))(2)/(R,R)-Me-DuPhos.National Natural Science Foundation of China[20832005]; National Basic Research Program (973 Program) of China[2010CB833200

We report the first one-pot reductive homocoupling reaction of secondary amides and cross-coupling reaction of secondary amides with ketones to give secondary vicinal diamines and amino alcohols. This method relies on the direct generation of α-amino carbon radicals from secondary amides by activation with trifluoromethanesulfonic anhydride, partial reduction with triethylsilane and samarium diiodide-mediated single-electron transfer. The reactions were run under mild conditions and tolerated several functional groups.