Release 24.3 - July 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.

• Re-run Shared Analyses: Re-run is now available for analyses that were shared with you.

• Limit Minimum Quantity: Select the desired minimum quantity that need to be available for commercial compounds to be considered starting materials (from 1 g to 500 g).
• Carbon Footprint: Check option to limit Starting Materials to compounds with available Spend-Based Emission Factors information according to the Environmentally Extended Input-Output (EEIO) model.
• Build Heterocycles from Scratch: Select new ‘Build Heterocycles’ option in the Saved Configurations menu to find pathways that build heterocycles from scratch, even when heterocyclic building blocks are published or commercially available.

• Carbon Footprint: Spend-Based Emission Factors information for commercial compounds is listed in their molecule card.
• Improved Search algorithm: Step sequence logic have been improved.
• Similarity Search: Similarity Search analyses for target molecules return results faster.

1058 new expert rules have been added, including rules for:

• Addition of primary amines to alkyl divinylphosphinates
• Alcoholysis of nitriles
• Alkylation of aryl phosphines
• Alkylation of N-heterocycles followed by dehydrohalogenation, deacetylation and separation of E,Z isomers
• Alkylation of nitriles followed by separation of diastereoisomers
• Alkylation of pyridinium N-oxides
• Asymmetric hydrogenation of alkenyl fluorides
• Asymmetric hydroxylamine-enone cascade reaction
• Asymmetric hydroxylamine enone cascade reaction
• Asymmetric transfer hydrogenation reaction
• Asymmetric Ugi four-component reaction
• Bisphosphorylation of carboxylic acids
• Bromination of double bonds
• Catalytic enantioselective dearomatization of pyrazines
• Catalytic stereoselective alkyne addition to nitrones
• Chiral resolution of diastereoisomers
• Chiral resolution of enantiomers
• Cobalt-catalyzed stereoselective cross-electrophile coupling
• Cobalt-catalyzed stereoselective hydroboration of alpha-substituted acrylates
• Cobalt-catalyzed stereoselective hydroboration of alpha-substituted acrylates followed by formation of trifluoroborates
• Cobalt-catalyzed stereoselective hydroboration of alpha-substituted acrylates followed by oxidation to primary alcohols
• Copper-catalyzed aminocyclization of N-propargyl hydrazones
• Copper-catalyzed modular difluoroalkylation
• Copper-catalyzed radical carbamylation cyclization
• Copper-catalyzed stereoselective ring-opening diboration of arylidenecyclopropanes
• Copper-catalyzed stereoselective ring-opening diboration of arylidenecyclopropanes followed by oxidation to alcohols
• Copper-mediated cyanodifluoromethylation of aryl halides
• Cyclization of hydroxyboronates
• Dechlorinative iodination of chloroarenes
• Deiodination of iodoarenes
• Deoxyphosphorylation of carboxylic acids
• Desilylation
• Diastereoselective decarboxylation
• Directed metalation followed by reaction with electrophile
• Enzymatic reaction oxidation of 2-aminopurines to guanines
• Enzymatic reaction primary amination of 1-aryl-2-alkyl alkynes
• Fluorination of sulfones
• Friedel-Crafts aminoalkylation
• Hydrogenation of cycloproponanes
• Hydrolysis of boronic esters to boronic acids
• Hydrophosphinylation of unactivated alkenes
• Intramolecular Friedel-Crafts cyclization
• Iridium-catalyzed reductive nucleophilic addition of nitriles to secondary amides
• Iron-catalyzed phosphorylation of alcohols
• Light-mediated decarboxylative trifluoromethylation of activated phenylacetic acids
• Light-mediated difunctionalization of [1.1.1]propellane
• Light and nickel-mediated decarboxylative aminomethylation of aryl bromides
• Matteson homologation
• Metallaphotoredox deoxydifluoromethylation of alcohols
• NHC-catalyzed radical cyclization addition cyclization cascade reaction
• NHC-catalyzed [3+3]-annulation
• Nickel-catalyzed stereoselective reductive coupling of aliphatic alkenes with imines
• Nickel-electrocatalyzed stereoselective reductive propargylic carboxylation with carbon dioxide
• Nickel-electrocatalyzed stereoselective reductive propargylic carboxylation with carbon dioxide followed by alkyne deprotection
• Nitrosation reaction
• Nucleophilic substitution with azides
• One-pot catalytic hydrophosphonylation of in situ-generated ketimines
• One-pot catalytic hydrophosphonylation of in situ-generated ketimines followed by phosphate ester hydrolysis
• One-pot catalytic Strecker reaction
• One-pot tandem Mizoroki-Heck olefination direct arylation hydrogenation sequence
• One-pot three-component synthesis of tricyclic dihydropyrazolone derivatives
• Oxidation of chloroguanines
• Ozonolysis of protected tetrahydropyrazines followed by hydrolysis
• Palladium-catalyzed asymmetric allylic substitution with chloroenolates
• Palladium-catalyzed oxidative coupling of anilines with 3-butenoic acid
• Palladium-catalyzed stereoselective functionalization of cyclobutenes
• Palladium-catalyzed [3+2] annulation via consecutive double Heck-type reaction
• Phosphorylation of aldehydes
• Photocatalytic decarboxylative phosphorylation of alpha-amino acids derivatives
• Photocatalytic deoxyphosphonylation of alcohols
• Photocatalytic difunctionalization of vinyl sulfonium cations
• Photocatalytic phosphonylation of N-ethoxypyridinium salts
• Photochemical [2+2] cycloaddition of alkynyl boronates followed by protodeborylation
• Photoinduced palladium-catalyzed stereoselective carboamination of dienes
• Photomediated ring contractions of N-aryl azacycles
• Photoredox deboronative phosphonylation
• Photoredox decarboxylative phosphonylation
• Preparation of allylboron dichloride
• Preparation of bromomethyl-1,2-azaborine
• Preparation of diazomethyl-1,2-azaborine
• Preparation of difluoro(trimethylsilyl)acetonitrile
• Preparation of dineopentyl(vinyl)sulfonium triflate
• Preparation of 1,2-dihydro-1,2-azaborine
• Radical-radical coupling
• Reduction of aliphatic hydroxylamines
• Reduction of alkenes
• Reduction of lactams
• Reduction of nitriles to amines
• Reduction of phosphine oxides to phosphines
• Reduction of phosphine sulfides to phosphines
• Reduction of tetrahydropyrazines
• Reductive coupling of phosphine oxides with aldehydes
• Resolution of E,Z isomers
• Rhenium-mediated intramolecular hydroarylation of alkenes
• Rhodium-catalyzed arylation of 1-bromo-2,2-difluoroethylene
• Rhodium-catalyzed synthesis of 3-arylbenzofuran-2-ylphosphines
• Ring-opening of epoxides and episulfides with thiolates
• Ruthenium-catalyzed oxidative cleavage of alkynes to carboxylic acids
• Selective Suzuki-Miyaura coupling of primary alkyl boronates with aryl bromides
• Selective Suzuki-Miyaura coupling of primary alkyl boronates with aryl iodide
• Simultaneous hydrolysis of lactams and esters
• Simultaneous reduction of lactams and esters
• Stereoselective 1,2-addition of allyl aryl ketones to 2,3-dioxopyrrolidines
• Stereoselective 1,4-addition of allyl aryl ketones to 2,3-dioxopyrrolidines
• Stereoselective benzylation of secondary phosphine oxide
• Stereoselective conjugate addition of 4-hydroxycoumarins to arylidenepyruvates
• Stereoselective deaminative alkylation of amino acid derivatives with unactivated olefins
• Stereoselective Strecker reaction
• Stereoselective Strecker reaction followed by amine deprotection
• Stereoselective Strecker reaction followed by deprotection
• Stereoselective synthesis of 2-azabicyclo[3.1.0]hexanes
• Stereoselective synthesis of alkyl fluorides via hydrofunctionalization of vinyl fluorides
• Stereoselective synthesis of ammonium cations
• Stereoselective synthesis of beta-amido carbonyls
• Stereoselective synthesis of spiroaminals
• Suzuki-Miyaura cross-coupling reaction
• Synthesis of 1,4-dihydro-1,6-naphthyridines
• Synthesis of 1,4-naphthoquinone-4-imines
• Synthesis of 1,6-naphthyridine derivatives
• Synthesis of 2-substituted buta-1,3-dienes from 1,4-dichlorobut-2-yne via organoboranes
• Synthesis of 4-iodo-7-aza-indazoles from 2-hydrazonylpyrimidines via intramolecular Diels-Alder reactions
• Synthesis of 6- and 7-aza-indazoles via intramolecular Diels-Alder reactions
• Synthesis of 7-aza-indazoles from 2-hydrazonylpyrimidines via intramolecular Diels-Alder reactions
• Synthesis of aryl(methylene)cyclopropanes
• Synthesis of boron-containing aromatic heterocycles
• Synthesis of cyclic phosphinic acids via Arbuzov reaction
• Synthesis of dihydropyridine and dihydropyrazolone derivatives
• Synthesis of diketopiperazines via cyclization reaction
• Synthesis of dipyrromethene BF2-complex
• Synthesis of dipyrromethenes
• Synthesis of enantioenriched 1-(chloro)alkylboronic ester
• Synthesis of gamma-lactams by multicomponent reductive coupling of nitroarenes, aldehydes and alkynes
• Synthesis of isoxazoles via [3+2] cycloaddition of nitrile oxides and enol ethers followed by elimination
• Synthesis of isoxazolines
• Synthesis of nitrones
• Synthesis of organophosphorus compounds via light-induced multicomponent reaction
• Synthesis of P,N-heterocycles via tandem aminomethylation cyclization reaction
• Synthesis of phosphine sulfides
• Synthesis of substituted arenes via pyridine skeletal editing
• Synthesis of [1,2,6]diazaphosphonine oxides
• Tert-butoxycarbonylation reaction
• Transfer hydrogenation reaction

Version 24.3 of SYNTHIA™ has been tested with Chrome versions 122.0.6261.112, 126.0.6478.62, 126.0.6478.115 and 126.0.6478.127, Microsoft Edge version 125.0.2535.7 on Windows 10 Enterprise, and Mac OS Sonoma 14.5.