Release 25.4 - December 2025

We are pleased to introduce a major enhancement in our latest release, designed to elevate user experience and overall functionality.

Introducing the SYNTHIA^® Whiteboard: A powerful new feature that streamlines brainstorming and design of synthetic pathways within SYNTHIA®. The Whiteboard enables:

• Seamless Integration: Select pathways, reactions, and molecules from your analysis results and transfer them effortlessly to a Whiteboard.
• Customizable Pathways: Create tailored pathways by combining reactions from multiple analyses, leveraging your expertise and insights.
• Integrated Molecule Editor: Use the built-in Molecule Editor to modify existing elements or draw new molecules and reactions directly on the Whiteboard.
• Collaboration Made Easy: Share your Whiteboards with team members to collaborate. Add comments, view shared input, and build synthetic pathways together.

2303 new expert rules have been added, including rules for:

• Acid-catalyzed dehydration of tertiary alcohols
• Acid-catalyzed hydrolysis of imines
• Acid-catalyzed synthesis of fused N-heterocycles
• Acid-catalyzed synthesis of pyrimidine derivatives
• Acid-catalyzed synthesis of pyrollopyrimidine derivatives
• Acylation of oxazolidinones
• Acylation reaction
• Addition of acetylenes to cyclobutanone derivatives
• Addition of acetylenes to cyclohexanone derivatives
• Addition of acetylenes to cyclopentanone derivatives
• Addition of lithiated heterocycles to aldehydes
• Aerobic oxidative alpha-alkylation of glycine derivatives with alkyl boronic acids
• Aldol condensation followed by decarboxylation
• Alkylation of alpha-silyl carboxylic acids
• Alpha-silylation of acetates
• Aluminum-catalyzed stereoselective synthesis of cis-beta-lactones
• Aluminum-catalyzed stereoselective synthesis of trans-beta-lactones
• Asymmetric acyl halide aldehyde cyclocondensations
• Asymmetric propargylic substitution of beta-hydroxy ketones
• Benzylic C-H carboxylation reaction
• Bromination of alkenes
• Catalytic stereoselective diboration of vinylboronates
• Chiral anion-mediated asymmetric Heck-Matsuda reaction
• Chlorination of benzylic position
• Cobalt-catalyzed Alder ene reaction
• Cobalt-catalyzed [2+2] cycloaddition
• Condensation of actetyloacetates with N-heterocycles
• Conjugate addition of alpha,beta-unsaturated ketones with in-situ formed arylzinc species
• Conjugate addition of aryl (pseudo)halides to activated olefins
• Copper-catalyzed asymmetric conjugate addition of organoboron reagents to alpha,beta-unsaturated carbonyl compounds
• Copper-catalyzed beta-boration of Michael acceptors
• Copper-catalyzed beta-boration of Michael acceptors followed by reaction with KHF2
• Copper-catalyzed deaminative cyanation of aliphatic primary amines
• Copper-catalyzed N-vinylation reaction
• Copper-catalyzed synthesis of tetrahydropyridines via nitrane-transfer radical relay process
• Corey-Chaykovsky cyclopropanation
• Coupling of vinyl bromide with N-heterocycles
• Cross-coupling of beta-tetrafluoroboratoenones with aryl bromides
• Cyclization via intramolecular opening of terminal epoxides
• Cycloaddition of nitrosoarenes with gem-difluorodienes
• Dabco-induced rearrangement of 2h-1,2-oxazin-3(6h)-one derivatives
• Deborylative alkylation of chiral 1,1,2-tris(boronates)
• Deborylative alkylation of chiral 1,1,2-tris(boronates) followed by oxidation of boronates
• Dehydratation of secondary alcohols
• Demethylation reaction with subsequent intramolecular transestrification
• Diastereoselective Corey-Chaykovsky cyclopropanation
• Double Friedel-Crafts reaction
• Elimination of cyclic secondary alcohols
• Enzymatic reaction: alcohol dehydrogenase-catalyzed asymmetric reduction of ketones
• Enzymatic reaction: alcohol dehydrogenase-catalyzed reduction of aldehydes
• Enzymatic reaction: alcohol dehydrogenase-catalyzed reduction of ketones
• Enzymatic reaction: alkaline protease from Bacillus subtilis-catalyzed Michael addition reaction
• Enzymatic reaction: benzil reductase-catalyzed stereoselective desymmetrization of 1,2-dicarbonyls
• Enzymatic reaction: biocatalytic synthesis of 3-aryl-2-oxazolidinones
• Enzymatic reaction: biocatalyzed, stereoselective reduction, nitrile hydrolysis of 2-oxocycloalkane carbonitriles
• Enzymatic reaction: biocatalyzed, stereoselective reduction of 2-oxocycloalkane carbonitriles
• Enzymatic reaction: carbonyl reductase-catalyzed asymmetric reduction of acetophenone derivatives
• Enzymatic reaction: chloroperoxidase-catalyzed asymmetric oxidation of sulfides
• Enzymatic reaction: DRKR-catalyzed reduction of aryl-alkyl ketones
• Enzymatic reaction: Fmo-catalyzed N-oxide synthesis
• Enzymatic reaction: ketoreductase-catalyzed asymmetric reduction of ketones
• Enzymatic reaction: KRED-catalyzed reduction of carbonyl compounds
• Enzymatic reaction: KRED-catalyzed regio- and stereoselectve reduction of dicarbonyl compounds
• Enzymatic reaction: KRED-catalyzed regio and stereoselectve reduction of dicarbonyl compounds
• Enzymatic reaction: lipase-catalyzed Michael addition to aromatic amines
• Enzymatic reaction: lipase-catalyzed synthesis of amido derivatives from 5-hydroxymethylfurfurylamine
• Enzymatic reaction: lipase-catalyzed synthesis of chiral amines and amides
• Enzymatic reaction: lipase-catalyzed synthesis of chiral amines and amides followed by hydrogenolysis
• Enzymatic reaction: lysozyme-catalyzed synthesis of 3-indolyl-3-hydroxy oxyindoles
• Enzymatic reaction: monooxygenase-catalyzed dynamic kinetic resolution of benzofused ketones
• Enzymatic reaction: monooxygenase-catalyzed oxidation of diketone
• Enzymatic reaction: P450-catalyzed allylic hydroxylation
• Enzymatic reaction: peroxygenase-catalyzed asymmetric epoxidation of alpha,beta-unsaturated aldehydes
• Enzymatic reaction: peroxygenase-catalyzed stereoselective benzylic hydroxylation
• Enzymatic reaction: proline hydroxylase-catalyzed selective hydroxylation of cyclic amino acids
• Enzymatic reaction: stereoselective synthesis of beta-azidoalcohols and beta-hydroxynitriles via one-pot adh- and halohydrin dehalogenase-catalyzed cascade
• Enzymatic reaction: styrene monooxygenase-catalyzed epoxidation of alkenes
• Esterification with subsequent intramolecular aldol condensation
• Gold- and platinum-catalyzed synthesis of substituted furanones via cycloisomerization
• Hofmann rearrangement
• Hydrogenation of alkenes
• Hydrogenolysis of N-O bonds
• Hydrolysis of esters
• Hydrolysis of silyl ethers
• Indium- and amine-catalyzed synthesis of functionalized cyclopentanes
• Intramolecular aldol reaction
• Intramolecular ring opening of azetidines and oxetanes
• Intramolecular transestrification of phenols
• Iridium-catalyzed stereoselective allylic substitution of vinyl aziridines
• Iridium-catalyzed stereoselective allylic substitution of vinyl epoxides
• Iron-catalyzed diastereoselective [4 + 1] cycloadditions of imines with sulfoxonium ylides
• Isomerisation of maleic to fumaric acid monoesters
• Lithiation of benzylic positions followed by reaction with electrophiles
• N-acylation of sulfoximines with carboxylic acids
• N-alkylation of 2-pyridones
• Nhc-catalyzed [2+2] cycloaddition of ketenes with oxoaldehydes
• Nickel-catalyzed asymmetric cross-hydrocarbonylation of unactivated alkenes
• Nickel-catalyzed cross coupling of aryl triflates and organic phosphine oxides
• Nickel-catalyzed enantioselective 1,4-addition of aryl halides to enones
• Nickel-catalyzed photoredox cross-coupling of aliphatic alcohols and n-hydroxylamine esters
• Nickel-catalyzed reductive cyclo-carboxylation of unactivated alkyl halides with CO2
• Nickel-catalyzed stereoselective arylboration of 1,3-cyclohexadiene
• Nickel-catalyzed stereoselective direct addition of styrenes to imines
• Nucleophilic substitution
• Nucleophilic substitution with azides
• One-pot metallaphotoredox cross-electrophile coupling and intramolecular ring opening of azetidines and oxetanes
• Opening of beta-lactones with azides
• Organocatalytic acid chloride-aldehyde cyclocondensation reaction
• Organocatalytic stereoselective synthesis of beta-lactones from ketenes and aldehydes
• Organocatalytic stereoselective synthesis of oxazolines with vinylogous isocyano esters
• Organocatalytic synthesis of functionalized beta-lactones
• 1,2-bis(boronate) homologation reaction with chloromethyllithium
• Palladium- and copper-catalyzed conjugate addition of aryl siloxanes
• Palladium-catalyzed aminocarbonylation of vinylcyclobutanols
• Palladium-catalyzed arylation of 1,2-amino alcohol derivatives via beta-carbon elimination
• Palladium-catalyzed arylation of cyclopropanols
• Palladium-catalyzed asymmetric 1,4-addition of arylboronic acids to 2,3-dihydro-4-pyridones
• Palladium-catalyzed conjugate addition to alpha-beta unsaturated carboxylic acids
• Palladium-catalyzed coupling of allylic alcohols and aryl bromides
• Palladium-catalyzed cross coupling of activated aryl chlorides and organic phosphine oxides
• Palladium-catalyzed cross coupling of aryl bromides and organic phosphine oxides
• Palladium-catalyzed cross coupling of aryl iodides and organic phosphine oxides
• Palladium-catalyzed intramolecular enyne coupling reaction
• Palladium-catalyzed stereoselective cross-coupling of cyclopropanols with aryl bromides
• Palladium-catalyzed stereospecific and regioselective allylic substitution
• Palladium-catalyzed synthesis of carbonyl compounds from allylic alcohols and aryl bromides
• Perfluoroalkylation of carbonyl compounds
• Photo- and electro-catalyzed iron(III)-mediated C-H fluoroalkylation reaction
• Photocatalytic fluoromethylation of alkenes and Michael acceptors
• Photocatalytic fluoromethylation of Michael acceptors
• Photocatalytic synthesis of fluorocarboxylated alcohols
• Photocatalytic synthesis of fluoromethylated alcohols
• Photocatalytic synthesis of fluoromethylated amines
• Photoredox nickel-catalyzed cross-coupling of secondary alkyl beta-trifluoroboratoketones and -esters with aryl bromides
• Preparation of (Z)-silyl enol ethers from alkyl phenyl ketones and trimethylsilyldiazomethane
• Preparation of 3,3-bis(bromomethyl)oxetane
• Prilezhaev reaction
• Rearrangement of caryophyllene
• Reduction of 2-oxazolidinones
• Regioselective hydroamidation of alpha,beta-unsaturated esters
• Rhenium-catalyzed intermolecular reaction of 1,3-dicarbonyl compounds with terminal acetylenes
• Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to 2,3-dihydro-4-pyridones
• Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to alpha,beta-unsaturated amides
• Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to Michael acceptors
• Rhodium-catalyzed carboamidation of beta,gamma-unsaturated carboxylic acids
• Ring expansion of cyclic ketones via reaction with trimethylsilyldiazomethane
• Ruthenium(ii)-catalyzed stereoselective synthesis of gamma-lactams by intramolecular C-H amidation of 1,4,2-dioxazol-5-ones
• Ruthenium-catalyzed alkyenylative cyclization
• Ruthenium-catalyzed conjugate addition of aryl boronic acids to alpha,beta-unsaturated carbonyl compounds
• Ruthenium-catalyzed cycloisomerization of dienes
• Ruthenium-catalyzed cycloisomerization of enynes
• Ruthenium-catalyzed olefin metathesis transfer-hydrogenation using formic acid
• Site-specific insertion of alkynes into unactivated amines
• Stereoselective cobalt-catalyzed arylation of Michael acceptors with aryl halides
• Stereoselective epoxidation of alkenes
• Stereoselective iodoetherification reaction
• Stereoselective palladium-catalyzed Suzuki-Miyaura cross-coupling
• Stereoselective synthesis of cannabidiol derivatives
• Stereoselective synthesis of homoallylic alcohols
• Stereoselective Zweifel alkenylation
• Stereoselective [2+2] cycloaddition of ketenes with oxoaldehydes
• Substitution of alkyl halide with alcohol
• Suzuki-Miyaura cross-coupling reaction
• Suzuki reaction of vinyl chlorides
• Syntheis of pyrrolotriazine derivatives
• Synthesis of 1,2-amino alcohols by Petasis reaction
• Synthesis of 2-bromoethyldiphenyl sulfide
• Synthesis of 2-oxaspiro[3.3]heptane derivatives
• Synthesis of 3-oxabicyclo[3.1.1]heptane derivatives
• Synthesis of alpha,beta-unsaturated ketones via Saegusa oxidation
• Synthesis of alpha-ketophosphonates
• Synthesis of aminopyrollopyrimidine derivatives
• Synthesis of aromatic alpha-ketoacids via Riley oxidation
• Synthesis of aryl-substituted pyrollopyrimidine derivatives
• Synthesis of aziridines through Smiles-Trauce rearrangement
• Synthesis of beta-disubstituted ketones via one-pot Meyer-Schuster rearrangement and asymmetric 1,4-addition reaction
• Synthesis of beta-N-heterocyclic-cyclobutane-fused bicyclic gamma-lactones from 2-hydroxycyclobutanone and carboxamide-bearing Wittig reagents
• Synthesis of chiral diols via hydrolytic kinetic resolution process
• Synthesis of chiral epoxides via hydrolytic kinetic resolution process
• Synthesis of cyclopropanes through Smiles-Trauce rearrangement
• Synthesis of dialkyl esters of maleic acid
• Synthesis of diarylalkynes from 2-butynedioic acid via palladium-catalyzed decarboxylative coupling reaction
• Synthesis of diarylalkynes from propiolic acid via palladium-catalyzed decarboxylative coupling reaction
• Synthesis of dihydropyridines
• Synthesis of enamines
• Synthesis of fused N-heterocycles via intramolecular cyclization of amides
• Synthesis of fused N-heterocycles via intramolecular cyclization reaction
• Synthesis of gamma-sultines through Smiles-Trauce rearrangement
• Synthesis of gamma-ylidenebutenolides
• Synthesis of hydroxypyrollopyrimidine derivatives
• Synthesis of lactones from homoallylic alcohols
• Synthesis of monoalkyl esters of fumaric acid
• Synthesis of monoalkyl esters of maleic acid
• Synthesis of N-sulfonyliminoiodinanes
• Synthesis of phosphorous ylide
• Synthesis of pyridazinones using hydrazines and gamma-ylidenebutenolides
• Synthesis of secondary carbinamines using Petasis reaction
• Synthesis of sulfonates
• Synthesis of symmetric diarylacetylenes via one-step stille coupling reaction
• Synthesis of terminal acetylenes via elimination of vinyl chlorides
• Tandem Lossen rearrangement condensation reaction
• Three-component asymmetric Tsuji-Trost reaction
• Titanocene-catalyzed [2+2] cycloaddition of enones
• Transition metal-catalyzed conjugate addition of aryl boronic acid to alpha,beta-unsaturated carbonyl compounds
• Visible light-catalyzed [2+2] cycloaddition of enones
• Wittig reaction
• Wittig reaction on furan-maleic anhydride cycloadduct followed by retro Diels-Alder reaction
• Zinc-mediated ring expansion and chain-extension reaction of beta-keto esters
• Zwitterion-catalyzed isomerisation of maleic to fumaric acid diesters

Version 25.4 of SYNTHIA® has been tested with Chrome versions 141.0.7390.109, 142.0.7444.163 and 142.0.7444.176 and Microsoft Edge Version 142.0.3595.94 on Windows 11 Enterprise and Mac OS Sequoia 15.6.1.