Darren Poole

Abstract

Asymmetric synthesis, reactions that produce a high proportion of one enantiomer of a chiral compound relatively to the other, are of ever-growing importance, particularly for creating pure pharmaceuticals. Asymmetric catalysis (1) uses a recyclable or regenerated chiral molecule to perform these reactions, but achieving high yields can be challenging if the substrate is relatively unreactive. On page 949 of this issue, Gatzenmeier et al. (2) report a highly efficient method that relies on an in situ–generated catalyst to produce complex structures in excellent yields of almost pure enantiomers from low-reactivity starting materials. Authors: Audrey Dumoulin, Geraldine Masson

The choice is yours: [Mo(CO)₆] is demonstrated to be an efficient catalyst for the chemoselective reduction of tertiary amides in the presence of a large number of reducible groups, including imines and aldehydes. The reaction is tunable by variation of the temperature, and either an amine or an aldehyde can be obtained as the major product from the corresponding amide. TMDS=1,1,3,3-tetramethyldisiloxane.

[Communication]
Fredrik Tinnis, Alexey Volkov, Tove Slagbrand, Hans Adolfsson
Angew. Chem. Int. Ed., March 02, 2016, DOI: 10.1002/anie.201600097. Read article

Wing it: The title reaction has been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. The method was applied for a concise synthesis of the antidepressant drug escitalopram. MTBE=tert-butyl methyl ether.

[Communication]
Linwei Huang, Jinbin Zhu, Guangjun Jiao, Zheng Wang, Xingxin Yu, Wei-Ping Deng, Wenjun Tang
Angew. Chem. Int. Ed., March 02, 2016, DOI: 10.1002/anie.201600979. Read article

A softer touch: Coordination of the tricarbonylchromium group to toluene derivatives not only facilitates deprotonation with lithium silylamide base, but convinces the resulting benzylic organolithium to reconsider its hardened ways and participate in palladium-catalyzed asymmetric allylic alkylation reactions with high enantioselectivity.

[Communication]
Jianyou Mao, Jiadi Zhang, Hui Jiang, Ana Bellomo, Mengnan Zhang, Zidong Gao, Spencer D. Dreher, Patrick J. Walsh
Angew. Chem. Int. Ed., January 12, 2016, DOI: 10.1002/anie.201509917. Read article

All smiles: Metal-free biaryl synthesis is achieved by adding benzyne to arylsulfonamides. A Smiles rearrangement enables CC bond formation, thus accessing a variety of functionalized biaryls under mild reaction conditions.

[Communication]
Catherine M. Holden, Shariar M. A. Sohel, Michael F. Greaney
Angew. Chem. Int. Ed., January 13, 2016, DOI: 10.1002/anie.201510236. Read article

Growing the chain: Asymmetric synthesis using terminal alkenes as substrates enables hydrocarbon-chain extension and concomitant functional-group installation. Given the ready availability of terminal alkene substrates, their enantioselective transformation represents a powerful synthesis strategy. FG=functional group.

[Minireview]
John R. Coombs, James P. Morken
Angew. Chem. Int. Ed., January 13, 2016, DOI: 10.1002/anie.201507151. Read article

Just a softy: Contrary to what would be predicted, organosodium nucleophiles derived from diarylmethane pronucleophiles are shown to behave as soft nucleophiles in nickel-catalyzed allylic substitution reactions. This general reaction is demonstrated to proceed through a double inversion pathway. A promising asymmetric version is presented.

[Communication]
Sheng-Chun Sha, Hui Jiang, Jianyou Mao, Ana Bellomo, Soo A. Jeong, Patrick J. Walsh
Angew. Chem. Int. Ed., December 03, 2015, DOI: 10.1002/anie.201507494. Read article

Migrate to create: Allylrhodium species from δ-trifluoroboryl β,γ-unsaturated esters undergo chain walking towards the ester moiety. The resulting allylrhodium species react with imines to give products with two new stereocenters and a Z-alkene. A chiral diene ligand leads to products with high enantioselectivities; a pronounced matched/mismatched effect with the chirality of the allyltrifluoroborate is evident.

[Communication]
Jose I. Martínez, Joshua J. Smith, Hamish B. Hepburn, Hon Wai Lam
Angew. Chem. Int. Ed., December 03, 2015, DOI: 10.1002/anie.201508964. Read article

Check the bod: Asymmetric alkynylation of cyclic α,β-unsaturated carbonyl compounds (ketones, esters, and amides) was realized by use of diphenyl[(triisopropylsilyl)ethynyl]methanol as an alkynylating reagent in the presence of a rhodium catalyst coordinated with a newly designed chiral diene ligand (Fc-bod). The reaction delivers high yields of the corresponding β-alkynyl-substituted carbonyl compounds with 95–98 % ee.

[Communication]
Xiaowei Dou, Yinhua Huang, Tamio Hayashi
Angew. Chem. Int. Ed., December 04, 2015, DOI: 10.1002/anie.201509778. Read article

No activation necessary: A nickel/chiral diphosphine (L) system effectively catalyzed the asymmetric allylic alkylation of β-ketoesters to deliver quaternary chiral centers at the α position of the β-ketoesters. The present system is highly advantageous in that it requires no activator for either the nucleophiles or the allylic alcohols.

[Communication]
Yusuke Kita, Rahul D. Kavthe, Hiroaki Oda, Kazushi Mashima
Angew. Chem. Int. Ed., December 04, 2015, DOI: 10.1002/anie.201508757. Read article

Three-in-one: The heteroarylation of aryl iodides and ortho-alkylation of the aryl rings occur in a single operation. The palladium and norbornene cocatalyst system effectively promoted the cleavage of two C-H bonds and the formation of two new C-C bonds, including a very hindered aryl–heteroaryl bond.

[Communication]
Chuanhu Lei, Xiaojia Jin, Jianrong (Steve) Zhou
Angew. Chem. Int. Ed., September 11, 2015, DOI: 10.1002/anie.201507128. Read article.

The construction of enantiomerically enriched tetrahydrofurans is accomplished by asymmetric Pd-catalyzed cross-coupling reactions between γ-hydroxyalkenes and aryl bromides. Use of a palladium catalyst supported by a new TADDOL-derived chiral phosphite ligand provides the tetrahydrofuran products in good yield with up to 96:4 e.r. (see scheme).

[Communication]
Brett A. Hopkins, Zachary J. Garlets, John P. Wolfe
Angew. Chem. Int. Ed., September 14, 2015, DOI: 10.1002/anie.201506884. Read article.

One-step alkylsulfonylation: A Pd-catalyzed one-step synthesis of (hetero)aryl alkyl sulfones from (hetero)arylboronic acids, K₂S₂O₅, and alkyl halides is described. This transformation is of broad scope, occurs under mild conditions, and employs readily available reactants. A stoichiometric experiment led to the isolation and characterization of a catalytically active dimeric Pd sulfinate complex.

[Communication]
Andre Shavnya, Kevin D. Hesp, Vincent Mascitti, Aaron C. Smith
Angew. Chem. Int. Ed., September 18, 2015, DOI: 10.1002/anie.201505918. Read article.