Chem 4D3 1998: Course Overview
Instructor: M. A. Brook, ABB 459, Lab ABB 465/466, Ext. 23483, E-mail:
mabrook@mcmaster.ca
3 lectures, one term. Some lecture periods will be used for tutorials.
Marking Scheme
| 4 Assignments (x 2.5) (to be submitted at the beginning
of class, late marks for late hand-in!) |
2.5
2.5
2.5
2.5 |
17 Sept.
15 Oct.
29 Oct.
19 Nov. |
1 Project
Presentation
Essay (at the beginning of class, late marks for late hand-in!) |
10
10 |
Nov. 12,13
Nov. 27 |
| 1 Test |
15 |
6 Nov. |
| 1 Final Exam |
55 |
TBA |
| Total |
100 |
|
Assignments are
due AT THE BEGINNING OF CLASS. ANY
ASSIGNMENTS HANDED IN LATER THAN THIS, without a medical excuse
approved by the Dean of Studies, may or may not be marked, but
WILL COUNT FOR ZERO!!
The Project/ Essay/ Presentation will consist
of groups of students presenting a topic related to synthesis (you may
suggest additional topics). You will choose the actual papers to present
in consultation with and APPROVAL BY ME! The presentation will consist
of a 40 minute presentation (with 10 additional minutes for questions)
by ALL MEMBERS OF THE TEAM. There will, in addition, be a 10-15 page (typed
double-spaced) essay summarizing your presentation. References required,
good quality pictures desired. The same grade will be awarded to all members
of the team.
Project Topics:
Antibiotics
Senate Policy Statements:
Attention is drawn to the Statement on Academic Ethics and the Senate Resolutions
on Academic Dishonesty as foun in the Senate Policy Statements distributed
at registration and available in the Senate Office. Any student who infringes
on the resolutions will be treated according to the published policy.
Course Outline
Review I
1 Acidity of functional hydrogens (CO2H, ROH, ketones, esters,
alkynes, etc.)
2 Practical bases R3N, tBuOK, NaH, LDA LiHMDS, MeLi,
BuLi
3 Protecting groups,
i ROH - ethers, acetals, silyl ethers, esters
ii Diols - acetals
iii RCO2H - esters
iv ketones - acetals, thioacetals
Synthetic strategy rules
1 linear versus convergent synthesis
2 disconnections
3 in the middle of molecules
i disconnect @ ring junctions
ii at or near functional groups
iii use hidden functional groups
Review II: Redox
Oxidation:
PCC, Jones, Swern, KMnO4, OsO4 (Sharpless dihydroxation),
KIO4, O3, mCPBA, Jacobson, Sharpless oxidation of
allylic alcohols
Reduction:
LiAlH4, NaBH4, dithianes / RaNi, Wolfe-Kishner,
Clemenson (ketones alkanes), HSi(TMS)3 AIBN (alkyl halides alkanes),
LiAlH4 + ROTs alkanes
Disconnections
Normal a1, d2, a3, etc.; for multiple
functional groups, pattern of 1,3; 1,5; use "normal" reactions, e.g. Aldol,
michael
Abnormal d1, a2, d3, etc.; for multiple
functional groups, pattern of 1,2; 1,4; 1,6;
i start with symmetrical molecules: alkynes, alkenes, cyclohexene
ii use abnormal reactions; perform umpolung; thioketals, cyanohydrins,
Grignard, bromination of ketones, nitromethane nitroethylene
iii use homologation, CN-, cyclopropanes
Enolate Chemistry
ketones a1, d2, thermodynamic versus kinetic generation
(more versus less substituted; E- versus Z-
alkylation (1, 2 with enolate, 3 with silyl enol ether)
enamines, thermodynamic control, enolate kinetic control
aldol reaction; Z syn Zimmerman-Traxler transition states
allyl tin anti-aldol
Ring formation
2+2; Diels-Alder, o/p vs m, endo rule; 3+2 cycloaddition
Rearrangements
Orbital controlled, e.g., Cope, Base or Acid-initiated, e.g., pinacol
Disconnections
More examples of synthetic strategy & road maps