C disconnections

The disconnections we have made so far have all been of C-O, C-N, or C-S bonds, but, of course, the most important reactions in organic synthesis are those that form C-C bonds. We can analyse C-C disconnections in much the same way as we ve analysed C-X disconnections. Consider, for example, how you might make this simple compound, which is an intermediate in the synthesis of a carnation perfume. 

The only functional group is the triple bond, and we shall want to use the chemistry of alkynes to show us where to disconnect. You know that alkylation of alkynes is a reliable reaction, so a sensible disconnection is next to the triple bond. 

Alkynes are particularly valuable as synthetic intermediates because they can be reduced either to cis or to irons double bonds. 

It s often a good idea to start retrosynthetic analysis of target molecules containing isolated double bonds by considering FGI to the alkyne because C-C disconnections can then become quite easy. 

This ds-alkene is a component of violet oil, and is an intermediate in the synthesis of a violet oil component, FGI to the alkyne reveals two further disconnections that make use of alkyne alkylations. The reagent we need for the first of these is, of course, the epoxide as there is a 1,2-relationship between the OH group and the alkyne. 

Before we leave C-X disconnections and go on to look at C C disconnections we should just review some important points. We suggested three guidelines for choosing disconnections and now that you have met the principle of two-group disconnections, we can add a fourth  

Two-group disconnections reduce the complexity of a target molecule more efficiently than one-group disconnections, and you should always be on the look-out for them. You will meet more two-group disconnections in the next section, which deals with how to disconnect C-C bonds. 

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Stereoelectronic control also plays a role in mechanistic stereoselectivity. One such case is the very fundamental 8 2 process which proceeds rigorously with inversion of configuration at carbon. Because of that intrinsic and predictable stereoselectivity, the C-C disconnective Sn2 displacement transform is very important even though it does not directly reduce the number of stereocenters, e.g. 153 => 154. 

Apply stereoselective transforms to reduce the number of reactive functional groups, especially those of sufficient reactivity to cause interference with stereocontrolled C-C disconnective transforms. 

Example Optically active acid (16) was needed (p T 107 ) for the synthesis of an ant alarm pheromone. The branch point ( in 16) is also the chiral centre so it is better to avoid disconnections there. The 1,2 C-C disconnection (16a) is ideal as it gives synthon (17), for which we use a malonate ester, and halide (18), available from optically active alcohol (19), a major by-product from fermentation. 

Answer This branched primary amine can be made from ketone (21) via the oxime (p T 63). A 1,2 C-C disconnection on (21) is good as it needs the symmetrical allylic halide (22). 

Optically active ketone (6) was needed for a study of asymmetric induction It could be made from acid (7) by a Friedel Crafts route or from nitrile (8) by Grignard addition, but neither of these compounds could be made by alkylation as the branchpoint is on the 3 carbon ( in each). The 1,3 C-C disconnection, e.g. (6b) is not good as it destroys the chiral centre. 

C-N disconnection requires difficult (38) so it is t-tter to look for C-C disconnect ions. The strategy of idding an activating group (39) to provide a 1,3-di- arbonyl disconnection is successful (cf p 204)-... 

Cool the reaction mixture in the flask to 0 °C. Disconnect mixer 3... 

Three combinations of Grignard reagent and ketone give rise to tertiary alcohols Disconnect R—C Disconnect R —C... 

We now leave disconnections of bonds between carbon and other atoms (C-X disconnections) and turn to the more challenging C-C disconnections. These are more challenging because organic compounds contain many C-C bonds and it is not clear at first which ones should be disconnected. There is some very good news the synthons that we met in chapter 6 for two-group C-X disconnections are the ones we shall use for one-group C-C disconnections. We start with an introduction to the three main types. In each case we shall replace one of the heteroatoms by a carbon unit R . 

The 1,3-diX relationship 12 was quickly recognised as conjugate addition to the enone 13 in chapter 6. The corresponding C-C disconnection 14 uses the same enone 13 but the nucleophilic carbon species should be a copper derivative RCu, R2CuLi or RMgBr with Cu(I)Br. 

It may be necessary to disconnect structural C-X bonds before doing the C-C disconnection as with the aminoester wanted for evaluation as an analgesic.2 Disconnecting the ester reveals... 

The simplest route to aldehydes and ketones using the same strategy is oxidation of an alcohol. So the analysis involves FGI back to the alcohol and then a C-C disconnection of one of the bonds next to the OH group. Lythgoe4 wanted to make a series of ketones 34 with various R groups to demonstrate a new alkyne synthesis. Disconnection of the C-R bond of the alcohol 35 meant that they could all be made from aldehyde 36 which can be made by the same strategy. 

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