ABSTRACT
The simple synthetic procedure for preparation of α-aryl-α-diazophosphonates via a diazo transfer reaction is proposed. Benzylphosphonates reacted with tosyl azide (TsN3) in the presence of potassium tert-butoxide (KOtBu) to afford diazophosphonates in a yield up to 79%. The proposed method is general. The reaction uses easily available starting materials, tolerates various functional groups, and may be applied for multi-gram scale synthesis.
ABSTRACT
Trifluorodiazoethane is a widely explored trifluoroethylating reagent, which is suitable for the preparation of a large number of fluorine-containing organic molecules. Nevertheless, CF3CHN2 has some disadvantages, such as volatility, storage instability, toxicity, and explosiveness. We report the application of trifluoroacetaldehyde N-tosylhydrazone as a CF3CHN2 precursor capable of generating in situ trifluorodiazoethane under mild basic conditions. Copper-catalyzed P-H, O-H, S-H, and C-H insertion reactions of trifluoroacetaldehyde N-tosylhydrazone revealed its wide applicability in the synthesis of trifluoroethyl-containing substances.
ABSTRACT
The reaction of fluorinated 1,6- and 1,7-enynes, containing the moiety N(PG)C(CF(3))(CO(2)R), with diazo compounds in the presence of [RuCl(cod)(Cp*)] (cod=cycloocta-1,5-diene, Cp*=C(5)Me(5) , PG=protecting group) as the catalyst precursor leads to the formation of fluorinated 3-azabicyclo[3.1.0]hexane-2-carboxylates and 4-azabicyclo-[4.1.0]heptane-3-carboxylates. This catalytic transformation was applied to various protecting groups and has proved to be a selective and a general synthetic tool to form constrained proline or homoproline derivatives in good yields. Z stereoselectivity of the created alkenyl group is obtained with N(2)CHSiMe(3), whereas N(2)CHCO(2)Et favours selectively the E configuration for the same double bond. The diastereoselectivity exo/endo depends on the size of the created ring. The X-ray structures of two products have been determined, showing the stereochemistry of the compounds. The reaction can be understood by initial [2+2] addition of the Ru=CHY bond, generated from diazoalkane, with the C≡CH bond of the enyne leading to a key bicyclic ruthenacyclobutane, which promotes the cyclopropanation, rather than metathesis. This selective formation of bicyclic [n.1.0] compounds results from the ruthenium-catalysed creation of three carbon-carbon bonds in a single step under mild conditions.
Subject(s)
Chemistry, Pharmaceutical/methods , Drug Discovery/methods , Esters/chemical synthesis , Fluorine/chemistry , Proline/analogs & derivatives , Proline/chemical synthesis , Alkynes/chemistry , Amines/chemical synthesis , Bridged Bicyclo Compounds/chemistry , Catalysis , Cyclization , Halogenation , Magnetic Resonance Spectroscopy , Methane/analogs & derivatives , Methane/chemistry , Molecular Structure , Organometallic Compounds/chemistry , Peptidomimetics/chemistry , Ruthenium/chemistry , StereoisomerismABSTRACT
The reaction of diazo compounds with enynes, containing a fluorinated amino acid moiety, in the presence of the precatalyst Cp(Cl)Ru(COD) leads to fluorinated alkenyl bicyclo[3.1.0]hexane and [4.1.0]heptane amino acid derivatives. It is remarkable that the catalyst, in situ generated from ruthenium complex and diazo compound, completely inhibits the ring closing metathesis of enyne to the profit of tandem alkenylation/cyclopropanation with high stereoselectivity. The study shows that the Cp(Cl)Ru moiety in ruthenacyclobutane favors reductive elimination versus expected alkene metathesis. [reaction: see text]
