Disconnections symmetry

Because of the symmetry of TM 329 there are only two different disconnections of bonds between two common atoms. 

The retrosynthetic analysis presented in Scheme 6 (for 1, 2, and 16-19) focuses on these symmetry elements, and leads to the design of a strategy that utilizes the readily available enantiomers of xylose and tartaric acid as starting materials and/or chiral auxiliaries to secure optically active materials.14 Thus by following the indicated disconnections in Scheme 6, the initially generated key intermediates 16-19 can be traced to epoxide 23 (16,19 =>23),... 

Example The substituted 1,4-diol (4) must surely be made by a method which uses the symmetry of the structure. Disconnection (a) would require Grignard reagent (5) whose OH group would have to be protected. Disconnection (b) gives hydroxy ester (6) and here no protection is necessary as the internal ester (lactone) (7) serves the purpose. 

Suggest a synthesis of symmetrical ketone (1). The symmetry is a help, so disconnect by opening both th nembered rings at once ... 

The symmetry of (32) suggests addition of an activating group followed by 1,3-dicarbonyl disconnection to symmetrical (33). This is a 1,6-dicarbonyl compound but reconnection gives (34) with no obvious disconnections. An alternative is to work back to readily available (37) by FGA and chain extension. 

Tho amino group must be left attached to a carbon atom next to a carbonyl group so we must disconnect bond (a) first. The next disconnection follows from the symmetry of (10). 

The recognition of a C2 axis of symmetry (or a plane, when the double bond was thought to have the cis configuration), allows the disconnection of the molecule into two identical moieties of indoxyl (2). The synthesis is therefore reduced to the... 

Owing to the D2 symmetry present in the structure of twistane only four "one single-bond" disconnections are possible (Scheme 13.1.1) ... 

Briefly we can say that, because of the nature of the search for retrons algorithm, the program finds the retron needed for disconnection with the Diels-Alder reaction twelve times, due to the symmetry of the cyclohexane molecule. With the option "Unique numbering" activated, the program is able to check whether the precursor about to be shown has already been shown. If it has, its display is suppressed. 

We saw symmetry put to good use at the end of the last chapter and it may well help if we can do two identical disconnections at once. The symmetrical tertiary alcohol 10 can be made from two molecules of a Grignard reagent 11 and one of ethyl acetate. Then back to the alcohol 12 by FGI and a disconnection at the branchpoint gives the starting materials. 

Wanting to study the photochemistry of a (3,y-unsaturated ketone that could not isomerise to a conjugated ketone, chemists5 chose 13. The obvious Wittig disconnection revealed the ketoaldehyde 14. Observing the symmetry of the carbon skeleton and the 1,3-relationship, they changed the ketone into an alcohol so that an aldol disconnection revealed two molecules of aldehyde 16. 

None of these relationships looks very promising, in part because any C-C disconnection would destroy the symmetry. We can get round this problem by using a trick that appeared first in chapter 19. We add an extra functional group (CC Me) to give us a 1,3-diCO relationship that can be disconnected 26 without destroying the symmetry. 

Two disconnections are possible. However, (a) is clumsy, because it does not respect the symmetry of the system. Using scheme (b) saves a great deal of effort. 

Now note symmetry. Doubly allylic disconnection keeps symmetry, requires activation (frames 57-8 and 101-2). 

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