A new one-pot hydroformylation/Strecker synthesis as a versatile synthetic tool for polyfunctional compounds and functionalization of dendrimers.

A versatile and high yielding one-pot hydroformylation/Strecker synthesis is reported for the synthesis of various alpha-aminonitriles. This methodology allows functionalization of dendrimers (e.g. polyamines 4-7) and hyper branched polymers (e.g. polyallyl glycerol 12) to give corresponding dendritic structures with alpha-aminonitriles and/or amino acids in the outer shell in good to excellent yields.

Application of iridium catalyzed allylic substitution reactions in the synthesis of branched tryptamines and homologues via tandem hydroformylation-Fischer indole synthesis.

Combination of enantioselective allylation reactions with a tandem hydroformylation-Fischer indole synthesis sequence as a highly diversity-oriented strategy for the synthesis of tryptamines and homologues was explored. This modular approach allows the substituents at C3 of the indole core, the type of the amine moiety, and the distance of the amine moiety to the indole core in the final synthetic step to be defined. The starting materials required for the hydroformylation step were synthesized via iridium catalyzed enantioselective allylic substitution reactions in high yields and excellent enantioselectivities. The Rh catalyzed hydroformylation step in the presence of phenyl hydrazine, allows the in situ formed aldehyde to be trapped as the hydrazone. Subsequent acid catalyzed indolization furnishes the desired indole structures in moderate to good yields.

Syntheses of tetrahydro-beta-carbolines via a tandem hydroformylation-Pictet-Spengler reaction. Scope and limitations.

A novel one-pot synthesis of tetrahydro-beta-carboline systems via tandem hydroformylation-Pictet-Spengler reaction starting from olefins and aryl ethylamines is described. This tandem procedure allows fast and convenient synthesis of various substituted tetrahydro-beta-carbolines.

A novel access to tetrahydro-beta-carbolines via one-pot hydroformylation/fischer indole synthesis: rearrangement of 3,3-spiroindoleninium cations.

The two component one-pot hydroformylation/Fischer indole synthesis sequence of 2,5 dihydropyrroles and phenyl hydrazines allows a facile and convenient access to tetrahydro-beta-carbolines in moderate to good yields.

Tetraoxane antimalarials and their reaction with Fe(II).

Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4' ') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg.kg-1.day-1, and 2/5 mice at 50 mg.kg-1.day-1, showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO* radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO* radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.

Synthesis of polyamines via hydroaminomethylation of alkenes with urea--a new, effective and versatile route to dendrons and dendritic core molecules.

Polyamines, structurally related to putrescines and spermidines, are easily obtainable via hydroaminomethylation of methylallylphthalimide with primary or secondary amines. In addition, hydroaminomethylation of monoolefins with urea as a synthetic equivalent for ammonia, in contrast to other methods (e.g. the alkylation of ammonia or ammonium salts), allows selective synthesis of symmetric tertiary amines. By combining both methods dendrons and dendrimer cores are conveniently obtained.

2,3-Disubstituted indoles from olefins and hydrazines via tandem hydroformylation-Fischer indole synthesis and skeletal rearrangement.

The tandem hydroformylation-Fischer indolisation protocol is used in the synthesis of 2,3-disubstituted indoles. After hydroformylation of selected olefins to form alpha-branched aldehydes in a one-pot procedure these are condensed with phenylhydrazine to give hydrazones. Upon acid-promoted [3,3]-sigmatropic rearrangement indolenine intermediates with quaternary centres in the 3-position are formed, which, after selective Wagner-Meerwein-type rearrangement of one of the substituents from the 3- to the 2-position, lead to 2,3-disubstituted indoles. Several olefins, bearing substituents with various functional groups, as well as cyclic olefinic systems are investigated.

Synthesis of pharmacologically relevant indoles with amine side chains via tandem hydroformylation/Fischer indole synthesis.

[reaction: see text] The sequence of hydroformylation and Fischer indole synthesis starting from amino olefins and aryl hydrazines is described. In a convergent manner, the two units bearing pharmacologically relevant substituents are assembled in the final indolization step. This modular and diversity-oriented approach to tryptamines and homotryptamines can be conducted in water and allows synthesis of branched and nonbranched tryptamines as well as tryptamine-based pharmaceuticals such as the 5-HT1D agonist L 775 606.

Tandem hydroformylation-hydrazone formation-Fischer indole synthesis: a novel approach to tryptamides.

A novel one-pot synthesis of indole systems via tandem hydroformylation-hydrazone formation-Fischer indolization starting from allylic amides and aryl hydrazines is described. This tandem procedure directly leads to biologically interesting tryptamides and analogues.

Highly regioselective synthesis of amino-functionalized dendritic polyglycerols by a one-pot hydroformylation/reductive amination sequence.

[reaction: see text] Dendritic architectures with neutral core structures and amines groups in the shell are a synthetic challenge, and there is a need for an efficient access. In this paper, highly selective Rh-catalysts are used for sequential hydroformylation/reductive amination of dendritic perallylated polyglycerols 1 with various amines in a one-pot procedure to give dendritic polyamines 3a-e in high yields (73-99%). In all cases, complete conversion of the allyl ether and aldehyde intermediate has been observed. Furthermore, the use of protected amines provides reactive core-shell-type architectures after deprotection. These soluble but membrane filterable multifunctional dendritic polyamines are of high interest as reagents in synthesis or as supports in homogeneous catalysis as well as nonviral vectors for DNA-transfection.

Sequential hydroformylation/aldol reactions: versatile and controllable access to functionalised carbocycles from unsaturated carbonyl compounds.

Three different modes of hydroformylation/aldol reaction sequences involving either acid-catalysed aldol reactions, Mukaiyama aldol addition of pre-formed enolsilanes or aldol addition of in situ generated boron enolates can be applied to unsaturated ketones and ketoesters to afford the corresponding carbocyclic aldol adducts in good yields proceeding through the intermediate activated ketoaldehydes. In selected cases, complimentary, synthetically useful diastereoselectivities were observed in the products.

Complexation of metals with piperazine-containing azamacrocyclic fluorophores.

Azamacrocyclic fluorophores containing piperazine units were synthesized using sequential rhodium-catalyzed regioselective hydroformylation-reductive amination. A piperazine unit is introduced into the macrocycles to act simultaneously as electron donor and binding site. The macrocycles chelate divalent cations, either Zn2+ or Co2+, which considerably enhanced fluorescence. Complexation with Zn2+ was additionally confirmed by NMR.

Sequential enolboration/hydroformylation/aldol addition: a new one-pot cascade reaction for the regio- and diastereoselective formation of carbocyclic quaternary centres from acyclic olefins.

Starting from unsaturated carbonyl compounds a mild new cascade reaction involving enolboration, rhodium-catalysed hydroformylation and intramolecular aldol addition in a regio- and diastereoselective fashion leads to cyclic compounds containing highly-functionalised quaternary carbon centres.

Tandem hydroformylation/Fischer indole synthesis: a novel and convenient approach to indoles from olefins.

[reaction: see text] A novel one-pot synthesis of indole systems via tandem hydroformylation/Fischer indole synthesis starting from olefins and arylhydrazines is described. This tandem procedure leads directly to 3-substituted indoles if unsubstituted phenylhydrazine is used and to 3,5- respectively 3,7-disubstituted indoles if para- or ortho-substituted arylhydrazines are used.

Synthesis of furo[2,3b]furans and furo[2,3b]pyrans via rhodium-catalyzed tandem hydroformylation/acetalization.

[reaction: see text] Rhodium-catalyzed tandem hydroformylation/acetalization of alpha,omega-alkenediols gives facile access to perhydrofuro[2,3b]furans and perhydrofuro[2,3b]pyrans in good yields. Similarly, benzoannelated tetrahydrofuro[2,3b]furans are obtained by hydroformylation of o-hydroxy cinnamyl alcohols.