Synthesis disconnections

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. 

A similar disconnection strategy was adopted by Dixon et al. in the United Kingdom in the synthesis of muricatetrocin The retro-synthesis disconnected the... 

The acid chloride (5) is used to protect amino groups in peptide synthesis. Disconnection of the ester bond gives simple starting materials, but the synthesis will require COCI2 (phosgene) to react once only with PhCHiOH. This succeeds since the half ester (S) is less reactive than the double acid chloride COCI2, because of conjugation (6). 

Regioselectivity of enolisation is still important. Acid (33) was used in a (very early ) stage of Woodward and Eschenmoser s vitamin B 2 synthesis. Disconnection gives an unsymmetrical ketone (8) and reactive, non-enolisable (34). Reaction in acid (page 154) ensured enolisation on the more substituted side of (8). 

The bicyclic double lactone (14) was used by Eschenmoser as the precursor for all four heterocyclic rings in his vitamin B12 synthesis. Disconnecting both lactones reveals a ketone (15). 

The rearrangement also works well with heterocycles compound (33), wanted for an alkaloid synthesis, disconnects to imine (34) which can be made from a benzylic cyanide (3S). The synthesis is uneventful. 

In connection with his work on insect pheromones, Silverstein wanted a general synthesis of optically active lactones (8). For a general synthesis, disconnection of R is best and as this also leaves a fragment > having the skeleton of available glutamic add (10), this route wm chosen, A series of trivial disconnections is needed, but this is a price worth paying for a readily available, optically active, starting material. 

Disconnection to 62 and 60 is reasonable and suggests an enolate alkylation condensation (Chapter 22, Section 22.9). Clearly, fragment 62 is complex and will require further disconnection to obtain reasonable starting materials. This is certainly a candidate for a convergent synthesis. Disconnection to 63 and 64 is not attractive because there is little simplification. Disconnection to 65 and 66 provides simplification. Fragment 65 may be correlated with a ketone, which will react via enolate alkylation (see Chapter 22, Section 22.9). This reaction requires... 

Retrosynthesis of 1,2,4-triazole reveals, that C-3 and C-5 are on the oxidation level of a carboxylic acid therefore, disconnections a-d are reasonable. Disconnections a, b, and c lead to acylated amidrazones 6-8 and further to amidrazones and carboxylic acids or their equivalents as possible educts for synthesis disconnections a and c lead to 1,2-diacyUiydrazines 7 and NH3 as starting materials. 

One of the low points of the first calcimycin synthesis is introduction of the pyrrole unit via an aldol condensation. The yields are bw and the stereocontrol at Ci9 Is probably marginal. The Grieco synthesis disconnects calcimycin between C213 and the 2-position of the pyrrole. Therefore a significant difference between this approach and the Evans approach Is an attempt to achbve better control of stereochemistry at C g. A secondary difference is that C was to be Introduced with complete control of stereochemistry rather than relying on thermodynamics for stereocontrol. It will be seen that a consequence of this plan is... 

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