Grignard reaction retro

Pyrrolotropone is formed by a thermal retro-Grignard reaction from a 4-aryl-4-hydroxycyclohepta[i]pyrrole derivative (72CB1224). Finally, cycloadditions of 8-styryl-l-azaazulenes with dimethyl acetylenedicarboxy-late and subsequent oxidation yield 1,7-ansa-bridged pyrrolotropones (80BCJ1406). 

A concise preparation of retinoids via new enaminodiesters synthons was described by Valla et al. [41]. For example, all -retinoic acid was synthesized within one day by a one-pot process. The enaminodiester synthon was prepared from methyl isopropylidenemalonate and dimethylformamide dimethylacetal (DMF-DMA) and then condensed with the lithium enolate of (3-ionone. A Grignard reaction with the obtained ketodiester led to the retro carbomethoxyretinoate. Saponification and concomitant decarboxylation, provided mainly all E retinoic acid (all E/ 3Z 90/10, 72% from P-ionone), Fig. (17). 

This disconnection represents the retro-Grignard reaction. It leads almost automatically to organomagnesium or lithium compounds as equivalents of carbanions and aldehydes or ketones as equivalents to the carbocation in the synthesis of alcohols (Scheme 2.35), or carbon dioxide in the synthesis of carboxylic acids. 

Often, our analysis of a TM will extend beyond a simple inspection of functional groups. It is also important to be on the lookout for characteristic patterns, or perhaps certain combinations of functional groups, as you consider the possible disconnections. If the TM is an alcohol, we already know that the Grignard reaction can be used to make it. However, if the alcohol TM has two identical groups attached at the carbon bearing the OH, then both of those carbon groups can be disconnected at the same time for one possible retro-synthesis. In this case, the synthesis would start with an ester, rather than a ketone or aldehyde, so the Grignard would be able to add twice. 

The Ci5 acetylene compound (425) was also used as a starting material for the synthesis of retro-18,14-retinol (435) via the acetylene alcohol (431), which was obtained from (425) and oligomeric formaldehyde by a Grignard reaction (Chauhan et al., 1982). 

Two routes to substituted butenolides involve modifications of earlier procedures based on retro-Diels-Alder reactions. 2-Substituted butenolides (46) can be obtained by alkylations of (45) followed by thermal degradation (Scheme 14) (45) is prepared from the cyclopentadiene-maleic anhydride adduct (44). 4,4-Dialkylbutenolides can be obtained from the Diels-Alder adduct of furan and maleic anhydride by sequential methanolysis, Grignard reaction, and... 

A multistage synthesis which well illustrates the use of Grignard reagents in carbon-carbon formation is the synthesis of 7-acetoxyheptanal (7).15 Retro-synthetic analysis reveals the necessity of aldehyde group protection as a 1.3-dioxane (8) (see p. 624) prior to the reaction process. 

Bicyclobulanolides A-substituted-1-butenolides. 1 Primary and secondary Grignard reagents react with the bicyclic anhydride 1 to form bicyclobulanolides (2) in 80-100% yield. Distillation of 2 effects a retro Diels-Alder reaction to give 4-disubstituted 2-butenolides (3). 

Highly hindered 4,4-diarylbut-2-en-4-olides (180) are prepared in good yield by Grignard addition to the anhydride (178) followed by a retro-Diels-Alder reaction (Scheme 100). ... 

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