Retrosynthetic analysis — E. J. Corey's disconnection-based planning of complex-molecule synthesis (Corey 1990 Nobel). Foundations: (1) Disconnection = retrosynthetic arrow ⇒; each disconnection identifies a target bond and specifies its…
retrosynthesis-strategy
Corey disconnection: retrosynthetic arrow ⇒ and synthon identification
Corey-style retrosynthesis (Corey & Cheng 1989) begins with the retrosynthetic arrow ⇒: the target molecule T is disconnected at a…
Functional-group interconversion tree: oxidation-state transforms
The functional-group interconversion (FGI) tree enumerates the oxidation-state-controlled transforms needed to move between target and…
Strategic-bond ranking: ring > stereocenter > C-heteroatom
Strategic-bond identification (Corey-Long-Rubenstein Science 1985; LHASA computer-assisted retrosynthesis) ranks candidate disconnections…
FGI C1 ladder: [-4,-2,0,2,4]; 2-unit steps; Σ = 0
Sympy-exact witness of the C1 oxidation-level ladder on the canonical methane → carbon-dioxide redox sequence. Setup: levels = [-4, -2, 0,…
n-ring σ-disconnection count = n; cyclohexane n=6 ⇒ 6
Sympy-exact symbolic witness of the n-ring disconnection-count identity. For any carbocyclic n-ring, the number of σ-bond disconnections…
Strategic-bond count = k-1 on k-stereocenter linear chain
Sympy-exact symbolic witness of the strategic-bond count on a linear chain bearing k consecutive stereocenters: |bonds between adjacent…
Woodward-Hoffmann framework: thermal (4n+2) disrotatory / 4n conrotatory; photochemical flip
Woodward-Hoffmann 1965 orbital-symmetry-conservation rules for thermal and photochemical electrocyclic reactions. For a polyene with…
Diels-Alder atom-economy framework: [4+2] cycloaddition conserves all atoms (atom economy = 1)
Diels-Alder [4+2] cycloaddition atom-economy analysis: the concerted 1,3-diene + dienophile → cyclohexene pericyclic reaction incorporates…
Seebach-Corey umpolung framework: a1 (natural electrophile) ↔ d1 (dithiane nucleophile) polarity flip
Seebach-Corey 1979 umpolung classification: the natural polarity of an sp²-carbonyl is a1 (acceptor at C, donor at O); dithiane protection…
W-H electrocyclic flags: 4π therm conrotatory; 6π therm disrotatory; 4π photo disrotatory (flip)
Classifier flags: 4π thermal → conrotatory; 6π thermal → disrotatory; 4π photochemical → disrotatory (flips). Canonical pins: three exact…
Diels-Alder atom economy = 1; byproduct mass = 0; new σ bonds formed = 2 (C1-C6 and C4-C5)
Stoichiometric invariants: atom economy = 1 (100%); byproduct mass = 0; new σ-bonds formed = 2. Canonical pins: three exact integers.
Seebach umpolung cancellation: a1 (natural +1) + d1 (dithiane −1) = 0 (polarity sum invariant)
Polarity arithmetic: natural carbonyl C = a1 (+1); dithiane C = d1 (−1); sum = 0. Canonical pins: three exact integers.
Corey retrosynthesis (1967)
E J Corey 1967 retrosynthetic analysis (Nobel 1990); disconnections + functional-group-interconversion; LHASA 1969 first computer-aided…
Synthon (Corey 1967)
Corey 1967 synthon = idealized fragment representing bond-forming function; e.g. acyl-cation synthon = acid-chloride; carbanion synthon =…
Chiral pool synthesis
Eschenmoser-Stork 1960s chiral-pool: terpenes + sugars + amino-acids as enantiopure starting materials; modern chiral-pool molecules count…
Protecting groups (Greene-Wuts)
Greene-Wuts handbook editions 1981+ 5th-2014: orthogonal protecting groups (Boc/Fmoc/Cbz amine; TBS/THP/Bn alcohol); modern PG-free total…
AI retrosynthesis (Segler 2018)
Segler-Preuss-Waller 2018 Monte-Carlo tree-search + neural-policy retrosynthesis; >80% success in random Reaxys targets; modern Chematica +…
Biocatalytic cascades (Bornscheuer 2018)
Bornscheuer 2018 enzymatic-cascade engineering; flow-chemistry merger; sitagliptin Codexis 2010 transaminase 9-step replaced by 1-step…
Retrosynthesis (Corey 1967)
E J Corey 1967 (Nobel 1990) retrosynthetic-analysis; modern OASIS + DENDRAL 1965 inspiration; AI-Synthesis Segler 2018 MCTS.
Synthon (Corey 1967)
E J Corey 1967 synthon abstraction; modern bond-disconnection + functional-group-interconversion + retron-pattern-matching.
Strychnine (Woodward 1954)
R Woodward 1954 (Nobel 1965) strychnine total-synthesis; modern asymmetric-organocatalysis + Vanderwal 2011 + Reisman 2018 routes.
Asymmetric-TM (Noyori 1980)
R Noyori 1980 + W Knowles 1968 (Nobel 2001) BINAP-Rh asymmetric-hydrogenation; modern Naproxen + L-DOPA + cefadroxil routes.
Organocatalysis (List-MacMillan 2000)
B List-D MacMillan 2000 (Nobel 2021) iminium / enamine catalysis; modern asymmetric counter-ion-directed + photoredox dual-cat.
Flow-chemistry (Jensen 2010)
K Jensen 2010 microreactor flow-chemistry; modern continuous-API + multi-step + mol-level Eli-Lilly-2016 prexasertib.