New bond. ph 4.0. Fischer esterification. New bond 2 O * New bond. New bond H 2N. New C-C bond. New C-C bond. New C-C bond. O Cl.

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1 Iverson C 0N KRE Table: For use in synthesis problems, count carbons in products and starting materials then identify location(s) of new s, especially C-C or C=C s. With that information, use the following KREs to determine which reactions are appropriate. KRE: A new C-C two carbons away from an - group indicates an organometallic reacting with an epoxide. KRE: A new C-C on the same carbon as a secondary - group indicates a Grignard reacting with an aldehyde. KRE: A new C-C on the same carbon as a tertiary - group indicates a Grignard reacting with a ketone. KRE: A new C-C on on a carboxylic acid in which one carbon atom was added indicates a Grignard reacting with C. KRE: A new C-C from a CN on the same carbon as an - group indicates CN reacting with a ketone or aldehyde. KRE: A new C-C from an alkyne on the same carbon as an - group indicates an alkyne anion reacting with a ketone or aldehyde. KRE: A new Z C=C indicates an alkyl Wittig reagent was used. New C=C KRE: A new E C=C indicates a Wittig reagent with a carbonyl adjacent to the negative charge (enolate Wittig) was used. E alkene KRE: An acetal where a carbonyl used to be indicates acetal formation with an alcohol. KRE: A five or sixmembered ring cyclic acetal where a carbonyl used to be indicates acetal formation with a two or three carbon diol. KRE: A five or six-membered ring cyclic hemiacetal indicates or -carbon hydroxyaldehyde starting material. N Z alkene C C C ) ) (mild) ) ) (mild) ) ) (mild) ) C ) (mild) C S (catalytic) S (catalytic) ) CN ) (mild) S (catalytic) or or CuLi Li P(Ph) P(Ph) KRE: An -hydroxy aldehyde with an indicates an aldol reaction with no dehydration. KRE: An imine indicates an aldehyde or ketone reacting with a primary amine or ammonia KRE: Ester group KRE: Amide group KRE: Two identical new C- C s on the same carbon as a tertiary - group indicates two equivalents of a Grignard reacting with an ester. KRE: A ketone with an new C-C adjacent to the carbonyl indicates an acid chloride reacting with a Gilman reagent. KRE: An,-unsaturated aldehyde with an E.Z mixture indicates an aldol reaction followed by dehydration in acid. KRE: This is an,-unsaturated aldehyde that indicates an aldol 6 reaction followed by dehydration. In this case the ring is formed because a 6-carbon dialdehyde is used. KRE: A -ketoester indicates a aisen reaction. KRE: This is a lactone (cyclic ester). The six-membered ring indicates a -carbon hydroxy acid starting material that undergoes Fischer esterification. New C=C E,Z Mixture N New C=C N S (catalytic) Na (catalytic) ) Na (catalytic) ) (mild) and heat ) Na (catalytic) ) (mild) and heat ) 0. eq. NaEt ) (mild) 6 N or ) N ) N ph.0 S (catalytic) ) (mild) ) (mild) Fischer esterification or CuLi KRE: This is a cyclic -ketoester that indicates a Dieckmann reaction starting with a 6-carbon diester. Notice that Dieckman reactions require.0 equivalent of base. KRE: This is a nucleophile linked to the -carbon of the amide. This is also a methyl ketone. Putting these together indicates a Michael reaction starting with acetoester KRE: Reaction of a nucleophile (-diketone) connected to the - carbon of a carbonyl (the ester) KRE: alkylated ketone deriving from either an enolate made with LDA or using an enamine KRE: A -diketone indicates reaction of an acid chloride with either an enolate made with LDA or using an enamine KRE: A methyl ketone with substitution at the -carbon indicates an acetoester synthesis. The second new C-C indicates a second alkylation with C Br KRE: A carboxylic acid with substitution at the -carbon indicates a malonic ester synthesis. KRE: This is a very tricky one. A symmetric ketone indicates a aisen reaction followed by ester hydrolysis and decarboxylation of the resulting - keto ester. 6 KRE: A new sixmembered ring with two new C-C s and an,-unsaturated ketone indicates a Robinson reaction. N ).0 eq. NaEt ) (mild) ).0 eq. NaEt ) N 7 8 ) (strong) and heat ).0 eq. NaEt ) ).0 eq. LDA ) Br ) ).0 eq. LDA ) ) ).0 eq. NaEt ) r ) (mild) r ) (mild) Br ) (mild) Br ).0 eq. NaEt ) C Br 6 N ) (strong) and heat ).0 eq. NaEt ) Br ) 0. eq. NaEt ) (strong) and heat ).0 eq. LDA 7 ) ) (mild) and heat N ) (strong) and heat 6

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