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An analytical approach to organic synthesis, designed to aid the design of synthetic routes.

The core of this system is the retrosynthesis, the imaginary reverse process to the synthesis of the target compound. Just as a synthesis consists of a series of chemical transformations that take starting materials to a target compound, a retrosynthesis takes the target compound back to starting materials using a series of disconnections. So, a disconnection is the reverse of a synthetic step, and is only made with a reliable forward reaction in mind.

The notation used for a disconnection is product ==> reactant (compare the notation for synthesis, reactant --> product). A bond that is broken in the disconnection (i.e. a bond that is made in the synthesis) is indicated by a wavy line drawn across the bond. Text can be written above and below the disconnection arrow to indicate the type of disconnection, or the forward reaction that the disconnection represents. For example, the formation of an ether from an alkyl halide and an alcohol:

Synthesis (forward direction):                  base
                               R--X  +  R'--OH  ---->  R--O--R'  +  HX
                               halide   alcohol         ether


Retrosynthesis (reverse direction):        C-O
                               R-|-O--R'  ====>  R--X  +  R'--OH
                                 ^        ether
     Line drawn across bond shows|
        position of disconnection|

C-O written above the disconnection arrow indicates a carbon-oxygen bond is being disconnected and ether below the arrow denotes the type of disconnection this arrow represents. The disconnection shown above leads to starting materials that are complete molecules. However, a more generalised disconnection will disconnect to synthons instead. A synthon is an idealised molecular fragment that may or may not be involved in the actual reaction, but helps us decided which starting materials to use.

For example, in the case shown above, the ether can be disconnection to the synthons R+ and R'--O-. Now, the alkyl halide is a reagent that is equivalent to the R+ synthon (in that it reacts in the same way that the imaginary R+ reagent would), but this disconnection is more general, in that it indicates that other reagents for R+ may be used (e.g. an alkyl tosylate, R--OTs).

Incidentally, a disconnection to R- and R'--O+ synthons is also valid, but reagents for these synthons may not be available, or the disconnection may lead to unknown or impossible chemistry in the forward direction. This 'unnatural polarity' is given the term umpolung, and reagents that produce these synthons are called umpolung reagents or umpoled reagents.

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