Organic Chemistry B

Course goals
The objective of the course is to make students develop a base of knowledge of the most fundamental organic reactions in the realm of organic synthesis.

Acquired skills
At the end of the course, the student should be able to select suitable reactions for a particular organic synthesis, based on the identification of the most effective possibilities among the available ones.

Course content
- Alkylation of enolates and other carbon nucleophiles. Generation and properties of enolates and other stabilized carbanions: generation of enolates by deprotonation; regioselectivity and stereoselectivity in enolate formation; other means of generating enolates; solvent effects on enolate structure and reactivity. Alkylation of enolates: alkylation of highly stabilized enolates; oxygen versus carbon as site of alkylation; alkylation of ketone enolates; alkylation of aldehydes, esters, carboxylates, amides, and nitriles; generation and alkylation of dianions; intramolecular alkylation of enolates; control of enantioselectivity in alkylation reactions. The nitrogen analogs of enols and enolates: enamines and imine anions. Problems.

- Reaction of carbon nucleophiles with carbonyl compounds. Aldol addition and condensation reactions: the general mechanism; mixed aldol condensations with aromatic aldehydes; control of regiochemistry and stereochemistry of mixed aldol reactions of aliphatic aldehydes and ketones; control of regio- and stereoselectivity of aldol reactions of aldehydes and ketones; aldol addition reactions of enolates of esters and other carbonyl derivatives; the Mukaiyama aldol reaction; control of facial selectivity in aldol and Mukaiyama-aldol reactions; intramolecular aldol reactions and the Robinson annulation. Addition reactions of imines and iminium ions: the Mannich reaction; additions to N-acyl iminium ions; amine-catalyzed condensation reactions. Acylation of carbon nucleophiles: Claisen and Dieckmann condensation reactions; acylation of enolates and other carbon nucleophiles. Olefination reactions of stabilized carbon nucleophiles: the Wittig and related reactions; reactions of carbonyl compounds with alpha-silylcarbanions; the Julia olefination reaction. Reactions proceeding by addition-cyclization: sulfur ylides and related nucleophiles; the Darzens reaction. Conjugate additions by carbon nucleophiles: conjugate addition of enolates; conjugate addition with tandem alkylation; conjugate addition by enolate equivalents; control of facial selectivity in conjugate addition reactions; conjugate addition of organometallic reagents; conjugate addition of cyanide ion. Problems.

- Electrophilic additions to carbon-carbon multiple bonds. Electrophilic addition to alkenes: addition of hydrogen halides, hydration, oxymercuration-reduction, addition of halogens, electrophilic sulfur and selenium reagents. Electrophilic cyclization: halocyclization, sulfenylcyclization and selenenylcyclization; cyclization by mercuric ion. Electrophilic substitution alpha to carbonyl groups: halogenations alpha to carbonyl groups; sulfenylation and selenenylation alpha to carbonyl groups. Additions to allenes and alkynes. Addition to double bonds via organoborane intermediates: hydroboration; reactions of organoboranes (transformations into alcohols, amines, halides); enantioselective hydroborations; hydroboration of alkynes. Hydroalumination, carboalumination, hydrozyrconation, and related reactions. Problems.

- Organometallic compounds of the group I, II, and III metals. Preparation, properties and reactions of organomagnesium, organolithium, organozinc, organocadmium, organomercury, organoindium, and organocerium compounds. Problems. Carbanions and other nucleophilic carbon species (acidity of hydrocarbons; carbanions stabilized by functional groups; enols and enamines; carbanions as nucleophiles in SN2 reactions). Problems.

- Blackboard exercises on the topics of the course.

Suggested prerequisites
Good knowledge of basic organic chemistry. Required passed exams: Organic Chemistry I, Organic Chemistry II, Laboratory of Organic Chemistry, Insights of Organic Chemistry.

Reference material
- F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Part B: Reactions and Synthesis, V Edition, 2007 Springer Science.
- F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Part A: Structure and Mechanisms, V Edition, 2007 Springer Science.

Assessment method
Written tests (3 tests "in itinere") and final oral examination. Each written test is typically comprised of 10-15 exercises taken from the recommended book (Carey & Sundberg, Part B). The final oral exam is mainly focused on a discussion of the written tests.

Language of instruction
Italian

Attendance policy
Compulsory (exercises)
Strongly recommended (lectures)

Mode of teaching
Traditional

Other information
Level of course: advanced