Synthesis Strategies Flashcards

Working backward from the target molecule to simpler starting materials. You identify the bonds that could have been formed last and determine what precursors are needed.

It means 'can be made from.' Unlike a reaction arrow, it points backward from product to starting material. Target => Precursor.

When a functional group would react with your intended reagent but you want it left untouched. Protect it before the reaction, then remove the protecting group afterward.

Convert it to a silyl ether using TBSCl or TMSCl. Remove later with fluoride (TBAF) or mild acid. This prevents the -OH from reacting with strong bases or nucleophiles.

Convert -OH to a tosylate (TsCl, pyridine) or mesylate (MsCl, Et3N). These are much better leaving groups than -OH for substitution reactions.

Use a cyanide nucleophile (NaCN) in an SN2 reaction to add -CN, then reduce or hydrolyze. Alternatively, use a Grignard reagent with formaldehyde.

Use an acetylide anion (formed by treating a terminal alkyne with NaNH2) as a nucleophile in an SN2 reaction with a primary alkyl halide.

An organomagnesium reagent (RMgBr) attacks a carbonyl. With formaldehyde: gives primary alcohol. With aldehyde: gives secondary alcohol. With ketone: gives tertiary alcohol.

Hydroboration-oxidation (BH3/THF followed by H2O2/NaOH). The -OH adds to the less substituted carbon.

Acid-catalyzed hydration (H2O/H2SO4) or oxymercuration-demercuration (Hg(OAc)2/H2O, then NaBH4). The -OH adds to the more substituted carbon.

Use PCC (pyridinium chlorochromate) in CH2Cl2. PCC is mild enough to stop at the aldehyde. Stronger oxidants like Jones reagent or KMnO4 will push it to the carboxylic acid.

Use NaBH4 (mild, selective for aldehydes/ketones) or LiAlH4 (stronger, also reduces esters and carboxylic acids). Both deliver hydride (H-) to the carbonyl carbon.

Changing one functional group into another without altering the carbon skeleton. Example: oxidizing an alcohol to a ketone, or reducing an alkene to an alkane.

Treat a ketone or aldehyde with base (LDA or NaOH) to form an enolate, which attacks another carbonyl. The product is a beta-hydroxy carbonyl (aldol product).

Fischer esterification: heat the carboxylic acid with an alcohol in the presence of an acid catalyst (H2SO4). Reversible reaction driven by excess alcohol.

An SN2 reaction between an alkoxide (RO-) and a primary alkyl halide to form an ether. Use a strong base (NaH) to deprotonate the alcohol first.

1) Identify the key bond or functional group that differs between starting material and product. 2) Work backward from the product. 3) Consider selectivity at each step. 4) Add protecting groups if needed.

Use SN2 for primary substrates when you need inversion of stereochemistry and predictable regiochemistry. Use SN1 only when racemization is acceptable and the substrate is tertiary.

Use dissolving metal reduction (Na/NH3). This gives the trans (E) alkene selectively via an anti addition of hydrogen.

Use catalytic hydrogenation with Lindlar's catalyst (Pd/CaCO3 poisoned with lead acetate and quinoline). This gives the cis (Z) alkene via syn addition.