Post on 30-Dec-2015
description
Synthetic Principles and Methodologies
Chung-Yi Wu
Assistant Research Fellow
Genomics Research Center
Tel: 02-2789-9930 ext 349
Email: cyiwu@gate.sinica.edu.tw
Text books
• Designing Organic Syntheses: A Programmed Introduction to the Synthon Approach. Stuart Warren Wiley, 1978.
• The Logic of Chemical Synthesis E.J. Cor
ey Wiley, 1989.
• Modern Organic Synthesis: An Introduction
• George S. Zweifel, Michael H. Nantz Freeman 2006.
• TM: target molecules.
• Retrosynthetic analysis (antithesis): The construction of a synthetic tree by working backward from the target molecule.
• Transfrom: The symbol signifies a reverse synthetic step.
• Disconnections: The main transforms are disconnections, or cleavage of C-C bonds, and functional group interconversions (FGI).
• Synthons: the fragments resulting from disconnection of C-C bonds of the TM.
• Synthetic equivalents (SE): The actual substrates used for the forward synthesis.
Chemical bonds can be cleaved heterolytically, homolytically, or through concerte
d transform
NucleophilicDonor
ElectrophilicAcceptor
Alternating Polarity Disconnections
• ? How one chooses appropriate C-C bond disconnections.
• Answer: The concept of alternating polarities or latent polarities (imaginary charges) often enables one to identify the best positions to make a disconnection within a complex molecule.
The positive charge (+) is placed at the carbon attached to the E class function group (e.g.,=O,-OH, -
Br)
Consonant pattern: Positives charges are placed at carbon atoms bonded to the E class groups
Dissonant pattern: One E class group is bonded to a carbon with a positive charge, whereas the other E class group resides on a carbon with a negative charge.
If a consonant pattern is present in a molecule, a simple syjthesis often be achieved
Sometimes, rather than protect one part of a molecule, it is better to activate another
(poor yield)
Illogical Two-Group Disconnection (Dissonant)
The 1,2-Dioxygenation Patterna-Hydroxy-Carbonyl Compounds