Release 24.4 - October 2024

We are constantly working to improve your experience with SYNTHIA™ Retrosynthesis Software. Here is a summary of what has changed with this latest release.

Diversity Library Analysis

• Build a library of up to 384 diverse analogues around a core structure derived from a parent molecule of choice, helping you assess which analogue compounds are easily accessible from a given synthetic pathway.
• Select which starting materials you want to substitute in the pathway to create one or more points of diversity around the core structure. SYNTHIA™ will look for commercially available or published starting materials that are compatible with the reaction conditions to build a library of analogue molecules. 
• Known Issue: Your original Automatic Retrosynthesis or Shared Path Library analysis must have both Commercial Compounds and Published Compounds lists enabled as Starting Materials. If one of the lists was disabled, you will not be able to create a Diversity Library from this analysis.

• Diverse Pathways Saved Configuration: New Saved Configuration that returns diverse pathways with no repeating disconnection schemes. This maximizes synthetic diversity and mitigates repeating disconnection patterns.

911 new expert rules have been added, including rules for:

• Addition of nitriles to nitrones followed by dehydration
• Alkylation of sulfonimidamides
• Amination of ethyl esters
• Amination of methyl esters
• Aromatic nucleophilic substitution followed by deprotection
• Asymmetric C-H borylation of aziridines ring-opening 1,2-metallate shift sequence
• Asymmetric C-H borylation of aziridines ring-opening 1,2-metallate shift sequence followed by amine deprotection
• Asymmetric C-H borylation of aziridines ring-opening 1,2-metallate shift sequence followed by oxidation and amine deprotection
• Aza-Matteson double-methylene insertions into nitrogen-boron bonds
• Aza-Matteson double-methylene insertions into nitrogen-boron bonds followed by Matteson homologation and oxidation
• Aza-Matteson double-methylene insertions into nitrogen-boron bonds followed by Morken amination
• Aza-Matteson double-methylene insertions into nitrogen-boron bonds followed by Suzuki coupling with aryl bromides
• Aza-Matteson mono-methylene insertions into nitrogen-boron bonds
• Aza-Matteson mono-methylene insertions into nitrogen-boron bonds followed by Suzuki coupling with aryl bromides
• Chiral resolution of diastereoisomers
• Chiral resolution of sulfonimidamide enantiomers
• Chiral resolution of sulfoxide enantiomers
• Chlorination of silylated sulfonamides
• Condensation of indoles and 1,2-phenylenediamines
• Copper-catalyzed aerobic oxidative coupling of o-phenylenediamines with 2-(hetero)arylethylamines
• Copper-catalyzed coupling of alkyl vicinal bis(boronates) to electrophiles
• Copper-catalyzed coupling of alkyl vicinal bis(boronates) to electrophiles followed by oxidation
• Copper-catalyzed coupling of alkyl vicinal bis(boronates) to electrophiles followed by oxidation and desilylation
• Copper-catalyzed coupling of alkyl vicinal bis(boronates) to electrophiles followed by oxidation of boronic esters
• Copper-catalyzed coupling of alkyl vicinal bis(boronates) to electrophiles followed by oxidation of boronic esters and dichloroalkenes
• Copper-catalyzed stereospecific cross-coupling of alkylboronates
• Copper-catalyzed stereospecific cross-coupling of alkylboronates followed by desilylation
• Copper-catalyzed stereospecific cross-coupling of alkylboronates followed by oxidation
• Coupling of allyl alcohols with aryl bromides
• Coupling of allyl alcohols with aryl iodides
• Coupling of azetidinones with aryl halides
• Coupling of thiazoles with aryl bromides
• Coupling of thiazoles with aryl iodide
• Cyclization of diamides to imidazolinones
• Deprotection of silylated sulfonimidamides
• Diastereoselective addition of grignard reagents to ketones
• Direct stereoselective alpha-C-H conjugate addition of propargylamines to alpha,beta-unsaturated ketones
• Electrophotocatalytic ritter-type amination of benzylic C-H bonds
• Formation of lactams via reduction of nitriles with subsequent cyclization
• Heterobenzylic difluorination
• Hydroalkylation of alkenes
• Hydrolysis of (carbamoyl)sulfonimidamides
• Hydrolysis of tert-butyl carbamates
• Hydrolysis of Weinreb amides
• Intramolecular stereoselective Pauson-Khand reaction
• Lithiation of vinyl dibromides
• Meta-selective C-H alkylation
• Meta-selective C-H arylation of benzylsulfonamides
• Meta-selective C-H arylation of benzylsulfonamides followed by hydrolysis
• Meta-selective C-H borylation
• Meta-selective C-H olefination of arenes
• Meta-selective C-H olefination of biphenyls
• Meta-selective C-H olefination of biphenyls followed by transesterification
• N-alkylation of 1,4-dihydropyridines
• Nickel-catalyzed regio- and stereoselective hydrocarboxylation of unactivated alkenes with CO2
• Nickel-catalyzed stereoselective 1,4-hydroamination of 1,3-dienes
• Nickel-catalyzed synthesis of sulfonamides
• Nickel-catalyzed synthesis of sulfonimidamides
• Nickel-catalyzed synthesis of sulfonimidoyl fluoride
• Nucleophilic aromatic substitution
• Opening of terminal epoxides
• Organocatalytic methylamination of arylboronic acids
• Organocatalytic methylamination of arylboronic esters
• Oxidation of delta-9-tetrahydrocannabinol core
• Palladium-catalyzed carbon monoxide insertion into O-nitrostyrenes
• Palladium-catalyzed electrooxidative double C-H arylation
• Palladium-catalyzed spirocyclization
• Para-selective C-H functionalization of pyridiens via oxazino pyridine intermediates
• Reaction of indirubins with hydroxylamine
• Reaction of isocyanates with N-protected sulfonimidamides
• Reaction of silylated sulfonimidamides with isocyanates
• Rhodium-catalyzed amination of tertiary C-H bonds
• Rhodium-catalyzed amination of tertiary C-H bonds followed by deprotection
• Ruthenium-catalyzed asymmetric hydrogenation of alpha,beta-unsaturated gamma-lactams
• Ruthenium-catalyzed asymmetric hydrogenation of alpha,beta-unsaturated gamma-lactams followed by PMP-deprotection
• Silylation of sulfonamides
• Site-selective defluorinative C-H alkylation of secondary amides
• Site-selective hydroxylation of pyridines via photoisomerization of pyridine N-oxides
• Site-selective isomerization-hydroboration of unactivated alkenes
• Site-selective isomerization-hydroboration of unactivated alkenes followed by oxidation
• Stereoselective addition of Grignard reagents to cyclic imines
• Stereoselective reduction of cyclic imines
• Stereoselective rhodium-catalyzed hydroboration of silyl enol ethers
• Stereoselective rhodium-catalyzed hydroboration of silyl enol ethers followed by desilylation
• Stereoselective rhodium-catalyzed hydroboration of silyl enol ethers followed by oxidation
• Stereoselective rhodium-catalyzed hydroboration of silyl enol ethers followed by tips deprotection
• Stereoselective synthesis of 2,3-disubstituted dihydrobenzofurans via one-pot C-H functionalization oxa-michael addition cascade
• Stereoselective synthesis of sulfoximines via ruthenium-catalyzed C-H functionalization
• Sulfonimidoylation of amines
• Synthesis of (pyrazolo)pyrimidines
• Synthesis of 1,2,4-oxadiazoles
• Synthesis of 1,4-diazines via condensation of 1,2 dicarbonyls and vicinal diamines
• Synthesis of 1,4-disubstituted pyrazoles
• Synthesis of 2-hydroxypyrimidines from isoxazoles
• Synthesis of 5-amino-1H-pyrazole-3-carbonitrile derivatives
• Synthesis of alkyl enol ethers
• Synthesis of aryl boraxines
• Synthesis of benzodiazaborines
• Synthesis of benzoimidazole derivatives
• Synthesis of benzoisoxales
• Synthesis of benzothiazole derivatives
• Synthesis of benzoxazaborines
• Synthesis of benzoxazole derivatives
• Synthesis of carboxylic acids via esters hydrolysis
• Synthesis of cyclic acetals from catechols and terminal alkynes
• Synthesis of homoallyl secondary boronates via cobalt-catalyzed regio- and stereoselective hydroboration reaction
• Synthesis of homoallyl secondary boronates via cobalt-catalyzed regio- and stereoselective hydroboration reaction followed by oxidation
• Synthesis of imidazo[1,5-a]pyridine derivatives
• Synthesis of imides from dicarboxylic acids and amines
• Synthesis of indirubins
• Synthesis of isochinolines via [5+1] heteroannulation of ynimine intermediates
• Synthesis of isoxazoles
• Synthesis of medium ring nitrogen heterocycles via tandem copper-catalyzed aryl amidation ring-expansion process
• Synthesis of morpholines via selective monoalkylation of amines
• Synthesis of N-protected sulfonimidoyl fluorides
• Synthesis of nitrones from aldehydes and nitro compounds
• Synthesis of oxazoles
• Synthesis of oxazoles followed by N-O bond cleavage
• Synthesis of pyrazoles
• Synthesis of pyridines via [5+1] heteroannulation of ynimine intermediates
• Synthesis of pyrimidines
• Synthesis of pyrolotriazines
• Synthesis of sulfonimidoyl chlorides
• Synthesis of symmetric secondary amines via reductive amination
• Synthesis of symmetric tertiary amines via exhaustive reductive amination
• Synthesis of thiazoles
• Synthesis of vinyl iodides
• Synthesis of ynimines
• Tert-butoxycarbonylation reaction
• Three-component sulfonimidamide synthesis
• Visible-light-promoted stereoselective alpha-amidation of aldehydes
• Witkop-Winterfeldt oxidation

Version 24.4 of SYNTHIA™ has been tested with Chrome versions 129.0.6668.101, 130.0.6723.58 and 130.0.6723.60, Microsoft Edge version 130.0.2849.52 on Windows 10 Enterprise, and Mac OS Sonoma 14.7.