Highly versatile enantioselective conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters.

Herein, we report efficient catalysts for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters. MeMgBr adds to aromatic alpha,beta-unsaturated thioesters with excellent enantioselectivities and moderate to good yields using Josiphos/CuBr and Tol-BINAP/CuI complexes. The use of bulky Grignard reagents leads to unprecedented enantioselectivities in the 1,4-addition to a broad range of aromatic and aliphatic alpha,beta-unsaturated thioesters using Tol-BINAP/CuI. The highest enantioselectivities reported so far for the addition of Grignard reagents to crowded beta-substituted aliphatic substrates are achieved with Tol-BINAP/CuI.

COMETARY SCIENCE. The landing(s) of Philae and inferences about comet surface mechanical properties.

The Philae lander, part of the Rosetta mission to investigate comet 67P/Churyumov-Gerasimenko, was delivered to the cometary surface in November 2014. Here we report the precise circumstances of the multiple landings of Philae, including the bouncing trajectory and rebound parameters, based on engineering data in conjunction with operational instrument data. These data also provide information on the mechanical properties (strength and layering) of the comet surface. The first touchdown site, Agilkia, appears to have a granular soft surface (with a compressive strength of 1 kilopascal) at least ~20 cm thick, possibly on top of a more rigid layer. The final landing site, Abydos, has a hard surface.

Catalytic enantioselective synthesis of naturally occurring butenolides via hetero-allylic alkylation and ring closing metathesis.

An efficient catalytic asymmetric synthesis of chiral γ-butenolides was developed based on the hetero-allylic asymmetric alkylation (h-AAA) in combination with ring closing metathesis (RCM). The synthetic potential of the h-AAA-RCM protocol was illustrated with the facile synthesis of (-)-whiskey lactone, (-)-cognac lactone, (-)-nephrosteranic acid, and (-)-roccellaric acid.

Copper catalyzed asymmetric synthesis of chiral allylic esters.

The complex derived from Taniaphos ligand 4 and CuBr*Me2S catalyzes the asymmetric addition of Grignard reagents to 3-bromopropenyl esters 1 to provide allylic esters 2 in high yields and high chemio-, regio-, and enantioselectivities. The work demonstrates that allylic asymmetric alkylation (AAA) can be done on substrates bearing a heteroatom at the gamma-position. The method is a practical route to chiral, nonracemic allylic alcohols. The use of functionalized substrates 1 or Grignard reagents leads to more complex products 2, which can be further manipulated as demonstrated in conversion to (S)-5-ethyl-2(5H)-furanone 6 and (S)-benzoic acid-cyclopent-2-enyl ester 7.

Catalytic asymmetric synthesis of acyclic arrays by tandem 1,4-addition-aldol reactions.

Herein, we report efficient acyclic stereocontrol in tandem 1,4-addition-aldol reactions triggered by catalytic asymmetric organometallic addition. Grignard reagents add to alpha,beta-unsaturated thioesters in a 1,4-fashion and the resulting magnesium enolates are trapped with aromatic or aliphatic aldehydes. The process provides a range of tandem products bearing three contiguous stereocenters with excellent control of relative and absolute stereochemistry. The various diastereomeric products have been fully characterized using single-crystal X-ray analysis and the origins of stereocontrol in this tandem protocol are discussed. The versatility and efficiency of this methodology are demonstrated in the first catalytic asymmetric synthesis of (-)-phaseolinic acid with 54% overall yield via a short and concise route.