A microwave-assisted, organocatalytic domino Michael/ Henry condensation/Michael/aldol condensation reaction has been developed. Employing acetaldehyde and nitroalkenes as substrates, this quadruple cascade allows an efficient asymmetric synthesis of trisubstituted cyclohexene carbaldehydes in moderate to good yields (25-45%) and high enantioselectivities (ee = 89 to >99%). ESI-MS measurements were carried out to support the proposed complex catalytic cycle.Over the last decade the area of organocatalysis has received much attention, evolving from a narrow field of research with fairly limited examples to one of the main branches in asymmetric catalysis. 1 Within this area, considerable attention has been paid to the development of highly stereoselective asymmetric domino reactions leading to complex molecular structures by convenient onepot protocols via a reaction cascade. 2 A large number of organocatalytic domino reactions have been developed over the last few years. 3,4 Our group, for example, published a diphenylprolinol-TMS-ether catalyzed triple domino reaction 5-9 that forms tri-and tetrasubstituted cyclohexene carbaldehydes. 4c,e-n As carbon-carbon bond forming reactions with acetaldehyde provide access to synthetically useful polyketides, many groups have tried to integrate acetaldehyde into aldol, Michael or Mannich reactions using enzymes, 10a,h trimethyl siloxyethenes as a synthetic equivalent 10e-g or organocatalysis. 10b-d The first synthetically useful organocatalytic reactions with acetaldehyde were reported in 2008 by the groups of List and Hayashi; these approaches involved secondary amine catalysed Michael, (self-)aldol and Mannich reactions. 10i-o Following these protocols, we envisaged a quadruple domino reaction of acetaldehyde with aromatic nitroalkenes, yielding trisubstituted cyclohexene carbaldehydes. To the best of our knowledge, only two amine-catalyzed quadruple domino reactions have been reported so far; these involved an oxa-Michael reaction followed by a Michael addition to a nitroalkene, a consecutive Michael addition of the resulting nitroalkane to an a,b-unsaturated aldehyde followed by an intramolecular aldol reaction. 11

An analytical procedure for the simultaneous determination in human serum of 43 common drugs of abuse and their metabolites belonging to the different chemical and toxicological classes of amphetamines, benzodiazepines, dibenzazepines, cocaine, lysergic acid diethylamide, opioids, phencyclidine, tricyclic antidepressants, and zolpidem, using 33 deuterated standards, is presented. The sample treatment was developed to be a very simple protein precipitation and filtration. All analyses were performed with a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry in positive ionization mode. All analytes were calibrated up to 550 μg/L. The limit of detection ranged from 0.6 ng/mL (EDDP) to 13.7 ng/mL (flunitrazepam). The method has been validated according to the guidelines of the Gesellschaft für Toxikologische und Forensische Chemie, using three multiple reaction mode (MRM) transitions and retention time for positive compound identification, instead of two MRMs, in anticipation of the new guidelines for January 2011.