Combining the regioselective room temperature/ambient pressure hydroformylation and a modification of the Doebner-Knoevenagel reaction allowed for the development of an efficient, onepot procedure for the synthesis of (E)-a,b-unsaturated carboxylic acids. The reaction proceeds under mild conditions, tolerates a variety of functional groups and gives (E)-a,b-unsaturated carboxylic acids in good yields and with excellent regio-and stereocontrol. The practicability of this process has been demonstrated by a short protecting group-free synthesis of the queen honeybee pheromones 9-ODA [(E)-9-oxodec-2-enoic acid] and 9-HDA [(E)-9-hydroxydec-2-enoic acid].

A combination of regioselective room-temperature/ambient-pressure hydroformylation (transition-metal catalysis) and decarboxylative Knoevenagel reactions (organocatalysis) allowed for the development of an efficient, one-pot C3 homologation of terminal alkenes to (E)-alpha,beta-unsaturated acids and esters, (E)-beta,gamma-unsaturated acids, (E)-alpha-cyano acrylic acids, and alpha,beta-unsaturated nitriles. All reactions proceed under mild conditions, tolerate a variety of functional groups, and furnish unsaturated carbonyl compounds in good yields and with excellent regio- and stereocontrol. Further, an iterative C2 homologation of (E)-alpha,beta-unsaturated carboxylic acids is possible through a combination of decarboxylative hydroformylation employing a supramolecular catalyst followed by decarboxylative Knoevenagel condensation with an organocatalyst.

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An efficient and simple to perform large-scale synthesis of o-and m-diphenylphosphinobenzoic acids is presented. In a single step, both useful carboxylic acid-functionalized phosphines can be accessed starting from the same inexpensive bulk chemicals o-chlorobenzoic acid, triphenylphosphine, and sodium. In both cases the formation of the desired product is controlled by the ratio of the starting materials only. Additionally, X-ray crystallographic data are reported for both products.Phosphines are widely applied and important donor ligands for transition metal catalysis. 1 Of particular use are phosphines equipped with appropriate functional groups, which allow for a modular ligand design through attachment to a variety of chiral and achiral backbones. Interesting examples of this class of ligands are the C2-symmetric Trost ligands, widely applied for asymmetric palladium-catalyzed allylic substitution. 2 These ligands are constructed by a modular design. Thus, chiral diols or diamines are connected through an ester or an amide linkage to the phosphine-binding post, with o-diphenylphosphinobenzoic acid (1, o-DPPBA) being the most important phosphine building block (Figure 1). Additionally, o-DPPBA (1) has found application as mediator in Staudinger ligation reacions 3 as well as catalyst-and reagent-directing group in a number of transition-metalcatalyzed and -mediated reactions. 4 Among them are the directed rhodium-catalyzed hydroformylation, 5c,6 conjugate addition 5 as well as the directed copper-mediated allylic substitution with Grignard reagents. 7 This methodology proved highly reliable for the construction of tertiary and quaternary stereocenters providing exceptional levels of acyclic stereocontrol, which has been applied in several natural product syntheses. 8 A drawback of this methodology has been the rather high costs of commercial o-DPPBA.The regioisomer of o-DPPBA (1) the m-diphenylphosphinobenzoic acid (2, m-DPPBA) is the basis for a variety of ligands (Figure 1), which have been applied for the Heck reaction and in allylic alkylation. 9 Moreover, we recently reported on the use of m-DPPBA (2) as a building block for supramolecular metallopeptide ligands for hydroformylation and asymmetric hydrogenation. 10 Figure 1 The o-and m-diphenylphosphinobenzoic acids 1 and 2Known total syntheses of m-and o-DPPBA (1,2) rely on halogen-lithium exchange reactions, on the use of Grignard reagents 11 or on the applications of transition-metalmediated coupling reactions. 12 Most of these syntheses suffer from low yields, multistep processes, or expensive starting materials. 11-13

2008 Carboxylic acids P 0250Practical Synthesis of (E)-α,β-Unsaturated Carboxylic Acids Using a One-Pot Hydroformylation/Decarboxylative Knoevenagel Reaction Sequence. -The synthetic value of this protocol is demonstrated by a protecting group-free synthesis of the queen honeybee pheromones 9-ODA (VIa) and 9-HDA (VIb). -(KEMME, S. T.; SMEJKAL, T.; BREIT*, B.; Adv. Synth. Catal. 350 (2008) 7-8, 989-994; Inst. Org. Chem. Biochem., Albert-Ludwigs-Univ., D-79104 Freiburg/Br., Germany; Eng.) -Nuesgen 37-056