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Organic Chemistry Highlights

Microwave Chemistry

Sunday, August 15, 2007
Doris Dallinger
Karl-Franzens-University Graz

Ketone Reduction via Transfer Hydrogenation

The group of Hans Adolfsson from Stockholm University has shown that ketones can be reduced to the corresponding alcohols via transfer hydrogenation in the absence of a transition metal catalyst when catalytic amounts of an alkali alkoxide are employed (Adv. Synth. Catal. 2007, 349, 1609. DOI: 10.1002/adsc.200700091). The reaction proceeded smoothly for a range of aromatic and aliphatic ketones using lithium isopropoxide (i-PrOLi) as catalyst and i-PrOH as hydrogen donor. Problematic ketone substrates, e.g. where R1 = CN or acetylpyridines that show coordination to the metal catalyst under traditional conditions can be converted to the alcohols in high yields. In addition, a scale-up from 0.5 mmol to 82 mmol for acetophenone (R1 = H, R2 = Me) was conducted employing a multimode instrument under the same reaction conditions giving the alcohol in similar isolated yield.

Synthesis of β-Amino Alcohols

The groups of Domingo Gomez Pardo and Janine Cossy from ESPCI-ParisTech, France, were successful in the stereoselective rearrangement of β-amino alcohols via an aziridinium intermediate under catalytic conditions (J. Org. Chem. 2007, 72, 6556. DOI: 10.1021/jo071028x). Linear N,N-dibenzyl β-amino alcohols 1 and N-benzyl prolinol (2) rearranged to β-amino alcohols 3 and 3-hydroxypiperidine (4), respectively, by treatment with 0.2 equiv of trifluoroacetic anhydride followed by saponification with 0.3 equiv of NaOH in high yields and excellent eeīs. Compared to the traditional method where stoichiometric amounts are employed, Et3N can be omitted from the procedure.

Palladium(II)-Catalyzed Conjugate Additions

Christian Wolf and Rachel Lerebours from Georgetown University, Washington, have reported on the palladium-phosphinous acid catalyzed conjugate addition of (het)aryl siloxanes to α,β-unsaturated substrates in water (Org. Lett. 2007, 9, 2737. DOI: 10.1021/ol071067v). Key to the success of a general method is the employment of 10 mol% of a copper co-catalyst (Cu(ACN)4PF6) additional to 5 mol% of the palladium catalyst POPd1. An advantage of the palladium-phosphinous acid catalyst POPd1 is the air and water stability that eliminates an inert atmosphere during the reaction. With this protocol, β-substituted ketones, aldehydes and nitroalkanes were obtained in high yields. Even otherwise difficult available β-substituted esters and nitriles can be generated smoothly in this way.

Dihydroquinoline and Quinoline Synthesis via Tandem Hydroamination-Hydroarylation

Chi-Ming Che and co-workers from the University of Hong Kong have developed a method for the synthesis of substituted 1,2-dihydroquinolines and quinolines under gold-catalysis (Org. Lett. 2007, 9, 2645. DOI: 10.1021/ol070814l). The reaction of anilines 1 with alkynes 2 employing the Au(I) catalyst 3/AgOTf combination afforded the corresponding dihydroquinolines 4 via a tandem hydroamination-hydroarylation sequence. By utilizing the proper substituted alkynes 2, products containing multiple alkyne groups can be obtained as well. Under similar conditions, quinolines 6 can be synthesized when alkynes are reacted with o-acetyl or -benzoyl substituted anilines 5.

D. Dallinger, Org. Chem. Highlights 2007, August 15.