Advanced synthesis
Graduate · Chemistry
Syllabus focus
Standard syllabus · STEM / applied
Pricing
Graduate-level rates are set on consultation. See the pricing page for K–12 and undergraduate rates.
Topics typically covered
Standard syllabus
Retrosynthetic analysis
- Disconnection approach and synthon concept
- Functional group interconversions (FGI)
- Strategic bonds and key disconnections
- Convergent vs linear synthesis planning
- Protecting group strategies for complex targets
- Stereochemical planning and chiral pool approaches
- Complexity-building reactions in retrosynthesis
- Computer-assisted retrosynthesis tools (overview)
- Evaluation of synthetic efficiency: step count, yield, scalability
- Literature precedent searching for synthetic routes
C–C bond formation methods
- Palladium-catalyzed cross-coupling: scope and limitations
- Nickel, copper, and iron catalyzed couplings
- Olefin metathesis in total synthesis
- C–H activation and directed functionalization
- Photoredox catalysis in synthesis
- Radical-based C–C bond formations
- Organocatalytic enantioselective reactions
- Asymmetric aldol, Mannich, and Michael additions
- Cycloadditions: Diels–Alder, dipolar, [2+2]
- Metal-catalyzed cyclization cascades
Heteroatom and functional group chemistry
- Selective oxidation and reduction methods
- Baeyer–Villiger, epoxidation, and dihydroxylation
- Amination and amination strategies (Buchwald–Hartwig, etc.)
- Fluorination and halogenation methods
- Glycosylation and oligosaccharide synthesis
- Peptide and macrocycle synthesis strategies
- C–N, C–O, C–S bond formation in complex settings
- Late-stage functionalization of advanced intermediates
- Boron and silicon chemistry in synthesis
- Click chemistry and bioorthogonal ligation in synthesis
Total synthesis case studies
- Classical total syntheses: strychnine, reserpine, morphine
- Modern approaches: palau'amine, brevetoxin, vinigrol
- Natural product-inspired methodology development
- Structure revision through total synthesis
- Biosynthetic pathway-inspired synthesis
- Diversity-oriented synthesis (DOS)
- Fragment coupling strategies for macrocycles
- Solid-phase and flow synthesis of complex molecules
- Scale-up challenges in total synthesis targets
- Critique of published syntheses: efficiency and innovation
STEM / applied
Laboratory execution
- Air-sensitive reaction setup and Schlenk techniques
- Low-temperature reactions and cryogenic chemistry
- Flash chromatography and preparative HPLC purification
- Reaction optimization: screening, DoE principles
- In-process analytical monitoring (TLC, LCMS)
- Handling hazardous reagents: organolithiums, azides, peroxides
- Process safety in scale-up of synthetic steps
- Documentation for GMP and process chemistry transfer
- Troubleshooting failed reactions and purifications
- Writing experimental sections for publications and patents
Applied synthesis
- Process chemistry in pharmaceutical manufacturing
- Fine chemical and agrochemical synthesis
- Contract manufacturing organization (CMO) workflows
- Green chemistry metrics in route selection
- Cost of goods (COGS) analysis for synthetic routes
- Intellectual property and freedom-to-operate in synthesis
- Automation and high-throughput reaction screening
- Flow chemistry for hazardous transformations
- Academic vs industry synthesis priorities
- Career paths in process, medicinal, and academic synthesis
Notes
Graduate-level organic synthesis. Topics reflect common advanced synthesis syllabi at US research universities. Strong organic chemistry background and laboratory experience expected.