ABSTRACT
A one-pot tandem Pd-catalyzed hydrostannylation/Stille coupling protocol for the stereoselective generation of vinyltins and their subsequent union, employing only catalytic amounts of tin, is described. By recycling the organotin halide Stille byproduct back to organotin hydride, a hydrostannylation/cross-coupling sequence can be carried out with catalytic amounts of tin. Such a process is most effective with Me(3)SnCl serving as the tin source. This protocol allows a 94% reduction of the tin requirement, while maintaining good yields (up to 90%) for a variety of Stille products. Furthermore, since one cycle requires the tin to undergo at least four transformations, each moiety of trialkyltin is experiencing a minimum of 60 reactions over the course of the hydrostannylation/Stille sequence.
Subject(s)
Organotin Compounds/chemistry , Organotin Compounds/chemical synthesis , Tin Compounds/chemistry , Tin/chemistry , Palladium/chemistry , StereoisomerismABSTRACT
[reaction: see text] Through a unified synthetic strategy, appropriately functionalized bicyclic starting materials can be elaborated via Ni(II)/Cr(II) macrocylization to [9.3.1] bicycles. Elaboration of these core structures allows access to phomactin C/D analogues and establishes the first synthetic approach to phomactin A affording an intact octahydrochromene/macrocyclic ring system.
Subject(s)
Guanidines/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Spiro Compounds/chemical synthesis , Animals , Chromium/chemistry , Epoxy Compounds , Fungi/chemistry , Humans , Marine Biology , Nickel/chemistry , Platelet Activating Factor/antagonists & inhibitors , Platelet Aggregation Inhibitors/chemical synthesisABSTRACT
A new tin recycling method for Stille couplings catalytic in tin is reported. PMHS made hypercoordinate by KF((aq)) allows Me(3)SnH to be efficiently recycled during a Pd(0)-catalyzed hydrostannation/Stille cascade. Relative to previously disclosed protocols, reaction times are shorter and because this process is believed to proceed through a Me(3)SnF intermediate the hazards and problems associated with trimethyltins are also diminished.[reaction: see text]
Subject(s)
Tin Fluorides/chemistry , Trimethyltin Compounds/chemistry , Catalysis , Palladium/chemistryABSTRACT
In a fraction of the time required by conventional methods, microwave-accelerated one-pot hydrostannylation/Stille coupling allows 1-alkynes to be efficiently transformed into 1,3-dienes or styrenes.
Subject(s)
Alkadienes/chemical synthesis , Organotin Compounds/chemistry , Styrenes/chemical synthesis , Alkadienes/chemistry , Alkynes/chemistry , Catalysis , Indicators and Reagents , Microwaves , Palladium , Styrenes/chemistryABSTRACT
[formula: see text] Lewis acid-catalyzed reaction of allyl and benzyl trichloroacetimidates with alpha-silyl alcohols was found to be a general method for the synthesis of alpha-alkoxysilanes. Upon exposure to CsF, these alpha-alkoxysilanes could be made to undergo [2,3]-Wittig rearrangement with an efficiency similar to that realized by the analogous but inherently more toxic alpha-alkoxystannanes.
Subject(s)
Silanes/chemical synthesis , Silanes/chemistryABSTRACT
[formula: see text] The Wittig rearrangements of alpha-alkoxysilanes, promoted by the action of methyllithium were studied. Depending on both the substrate and reaction conditions employed, [2,3]-, [1,2]-, or [1,4]-Wittig rearrangements can be realized. These rearrangements were shown to be initiated by either Si/Li exchange or deprotonation alpha to the silane. Furthermore the sigmatropic shifts can often be followed by other synthetically useful in situ chemical events.
Subject(s)
Alkanes/chemistry , Lithium/chemistry , Silanes/chemistryABSTRACT
A series of new arylfluoroquinolones has been prepared. These derivatives are characterized by having fluorine atoms at the 6- and 8-positions, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position. The in vitro antibacterial potency is greatest when the 1-substituent is 2,4-difluorophenyl and the 7-substituent is a 3-amino-1-pyrrolidinyl group. 1-(4-Fluorophenyl)-6,8-difluoro-7-piperazin-1-yl-1,4-dihydro-4-oxo quinoline-3- carboxylic acid (22) was found to possess excellent in vitro potency and in vivo efficacy.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Quinolines/chemical synthesis , Animals , Bacterial Infections/drug therapy , Female , Fluorine/pharmacology , Fluorine/therapeutic use , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Microbial Sensitivity Tests , Quinolines/pharmacology , Quinolines/therapeutic use , Spectrophotometry, Infrared , Structure-Activity RelationshipABSTRACT
A series of novel arylfluoroquinolones has been prepared. These derivatives are characterized by having a fluorine atom at the 6-position, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position. Structure-activity relationship (SAR) studies indicate that the in vitro antibacterial potency is greatest when the 1-substituent is either p-fluorophenyl or p-hydroxyphenyl and the 7-substituent is either 1-piperazinyl, 4-methyl-1-piperazinyl, or 3-amino-1-pyrrolidinyl. The electronic and spatial properties of the 1-substituent, as well as the steric bulk, play important roles in the antimicrobial potency in this class of antibacterials. As a result of this study, compounds 45 and 41 were found to possess excellent in vitro potency and in vivo efficacy.
