Difunctionalised compounds

Two-Group Disconnections II 1,3-Difunctionalised Compounds and (X, d-Unsaturated Carbonyl Compounds... 

Two-Group Disconnections III 1,5-Difunctionalised Compounds Michael Addition and Robinson Annelation... 

We prefer to disconnect the right hand half of the molecule in this way because optically active lactones (59) can be made from glutamic acid (60), another available 1,4-difunctionalised compound (p T 96 ). 

Strategy XII Reconnections Synthesis of 1,2- and 1,4-Difunctionalised Compounds by C=C Cleavage... 

Ozonolysis of condensation products can provide a route to 1,2-difunctionalised compounds. Camphor (13) condenses with many carbonyl compounds (HC02Et is used here) at its only free a-CH2 group to give, e.g. (14). Ozonlysis releases the a-diketone (15). 

Diol (7) can dehydrate only to (6) it is a 1,6-difunctionalised compound which can be made from an adipic diester (8), and hence from cyclohexene. Dehydration occurs readily in acid solution to give a high yield of TM (6),... 

Tr.e cyclic amino acid (25) could be made from a,e-di-cromo acid (26) and this can be made from (27) by a-trominatlon and replacement of hydroxyl by Br. This 1, 6-difunctionalised compound (27) is simply the ring -pened form of lactone (28), the Baeyer-Villiger p T 226) cleavage product from cyclohexanone. 

Figure 7-37. The reaction of a difunctionalised molecular thread with another difunctionalised compound to give a macrocyclic product.

The next 10 chapters are about the synthesis of carbon skeletons with two functional groups. Compounds such as 1-3 will all be treated as 1,3-difunctionalised compounds since the important thing is not the type of functional group but the relationship between them. Our logic is that all FGs can be derived from alcohols, ketones (or aldehydes) or acids by substitution and that those three can be interconverted by oxidation or reduction. 

Synthesis of difunctionalised compounds with odd numbered relationships needs only synthons of natural polarity. 

Synthesis of difunctionalised compounds with even numbered relationships needs some synthons of unnatural polarity. 

Epoxides give rise to many 1,2-difunctionalised compounds such as 48 with control over stereochemistry. Reactions of the epoxide 49 from 44 give the anti stereochemistry in 48 in contrast to the syn stereochemistry in 43. Other compounds made from alkenes include 1,2-bromides and bromohydrins from reaction with bromine alone or bromine and water. 

This reaction - the benzoin condensation17 - is the nearest we have come to realising the simplest strategy of acyl anion and carbonyl electrophile in one step. One important group of reactions that make 1,2-difunctionalised compounds is the subject of the next chapter on radical reactions. A more modem version of this reaction, not needing cyanide, is described in chapter 39. 

The problem of unnatural polarity also arises in making C-C disconnections for the synthesis of 1,4-difunctionalised compounds. If we start with 1,4-diketones 1, disconnection in the middle of the molecule gives a synthon with natural polarity 2, represented in real life by an enolate 4, and one of unnatural polarity, the a2 synthon 3 represented by some reagent of the kind we met in chapter 6 such as an a-haloketone 5. 

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