Subject(s)
Alanine/analogs & derivatives , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Alanine/chemical synthesis , Alanine/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Catalysis , Crystallography, X-Ray , Cyclization , Models, Molecular , Molecular Conformation , Oxidation-Reduction , StereoisomerismABSTRACT
Five and six ring a-phosphono lactams 14-20 are available by reaction of 1,2- and 1,3-cyclic sulfamidates respectively with enolates derived from ethyl dialkylphosphonoacetates 3 and 4. Subsequent Wadsworth-Emmons olefination provides the enantiomerically pure exo-alkylidene variants e.g. 25, which is efficiently converted to vinyl triflate 29 (> 98% ee). Suzuki coupling of 29 to a range of aryl and vinyl boronic acids leads to a structurally diverse range of pyrrolidinones exemplified by 30 and 34. The degree of epimerisation at the base-sensitive C(5) stereocentre during the Suzuki coupling of 29 is shown to be dependent on both the nature of the aryl boronic acid and the reaction conditions used.
Subject(s)
Ketones/chemistry , Lactams/chemical synthesis , Organophosphonates/chemistry , Sulfonamides/chemistry , Cyclization , Lactams/chemistry , Molecular Structure , StereoisomerismABSTRACT
The reaction of the dienolate of ethyl acetoacetate (and related dienolates) with a range of 1,2- and 1,3-cyclic sulfamidates provides an entry to substituted and enantiopure alkylidenated pyrrolidines and piperidines. These heterocycles function as convenient precursors to heterocyclic beta-amino acid derivatives.
Subject(s)
Piperidines/chemical synthesis , Pyrrolidines/chemical synthesis , Sulfur Compounds/chemical synthesis , Alkylation , Amination , Cyclization , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Molecular Structure , Piperidines/chemistry , Pyrrolidines/chemistry , Sulfur Compounds/chemistryABSTRACT
1,2-Cyclic sulfamidates undergo efficient and regiospecific nucleophilic cleavage with 2-bromophenols (and related anilines and thiophenols), followed by Pd(0)-mediated amination to provide an entry to substituted and enantiomerically pure 1,4-benzoxazines (and quinoxalines and 1,4-benzothiazines). This chemistry provides a short and efficient entry to (3S)-3-methyl-1,4-benzoxazine 19, a late stage intermediate in the synthesis of levofloxacin.
Subject(s)
Levofloxacin , Ofloxacin/chemical synthesis , Anti-Infective Agents/chemical synthesis , Benzoxazines/chemistry , Stereoisomerism , Sulfonamides/chemistryABSTRACT
Short and efficient enantioselective syntheses of (-)-paroxetine and (+)-laccarin are described based on the highly stereospecific cleavage of C(3)-substituted 1,3-cyclic sulfamidates.
Subject(s)
Indoles/chemical synthesis , Paroxetine/chemical synthesis , Piperidines/chemical synthesis , Stereoisomerism , Sulfonic Acids/chemistryABSTRACT
A full account of studies which led to the efficient asymmetric synthesis of (-)-aphanorphine is reported. Two routes to the key cyclic sulfamidate intermediate are described, the first was based on a chiral auxiliary approach and the second utilised asymmetric hydrogenation methodology. A range of C(3)-substituted lactams (, and ) were synthesised and evaluated as precursors for Pd(0) catalysed entries (based on (i) alpha-arylation of a lactam enolate and (ii) reductive Heck reaction) to the 3-benzazepine core of . These approaches were less effective than an aryl radical cyclisation which allowed the completion of a synthesis of in 12 steps from anisaldehyde.
Subject(s)
Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/chemical synthesis , Cyclic S-Oxides/chemistry , Lactams/chemistry , Pyrroles/chemistry , Pyrroles/chemical synthesis , Combinatorial Chemistry Techniques/methods , Cyclization , Molecular Structure , Sulfonamides/chemistryABSTRACT
A structurally representative series of 1,2- and 1,3-cyclic sulfamidates react with enolates derived from methyl alpha-phenylthioacetate 9b to give 5- and 6-substituted alpha-phenylthio lactams 20-24. These products provide, via the corresponding sulfoxides, an entry to alpha,beta-unsaturated lactams e.g. 12, 27, 29 and their alpha-phenylthio analogues e.g. 26 and 30. With the enantiomerically pure 1,2-cyclic sulfamidates 10, 15 and 17, these reactions all proceed with no detectable loss of stereochemical integrity.
Subject(s)
Lactams/chemical synthesis , Sulfones/chemistry , Glycolates/chemistry , Lactams/chemistry , Stereoisomerism , Sulfonic Acids/chemistryABSTRACT
A short and efficient enantioselective synthesis of (-)-aphanorphine is described based on the use of a cyclic sulfamidate to provide a suitably functionalised lactam that allows for construction of the tricyclic 3-benzazepine scaffold.
Subject(s)
Amides/chemistry , Bridged-Ring Compounds/chemistry , Lactams/chemistry , Pyrroles/chemistry , Sulfur/chemistry , Molecular Structure , StereoisomerismABSTRACT
[reaction: see text] A structurally diverse series of mono- and disubstituted 1,2- and 1,3-cyclic sulfamidates react with stabilized enolates, including malonate and phosphonoacetate variants, to provide, after lactamization, substituted and alpha-functionalized pyrrolidinone and piperidinone derivatives.
ABSTRACT
An entirely two-directional synthesis of (+/-)-perhydrohistrionicotoxin is presented, utilizing a tandem oxime formation/Michael addition/[3 + 2] cycloaddition as the key step. This approach also constitutes formal syntheses of (+/-)-histrionicotoxin and (+/-)-histrionicotoxin 235A.
