Retro-Michael disconnection

Now 1,5-disconnection (a) in Scheme 4.35 is preferred, resulting with a-isopropyl ethyl acetoacetate, an easily available TM 4.11c. retro-Michael disconnection (b) in TM 4.11b is not possible since no double bond can be formed to the quaternary C-atom. 

Intramolecular retro-Michael disconnection of the y-nitro ester and opening of the cyclohexane ring provide an innovative retrosynthetic concept. Next, retro-Michael disconnection splits the aromatic unit from the unsaturated nitro ester. 

The Y appendage of 2-cyclohexenone 191 cannot be directly disconnected by an alkylation transform. (y-Extended enolates derived from 2-cyclohexenones undergo alkylation a- rather than y- to the carbonyl group). However, 191 can be converted to 192 by application of the retro-Michael transform. The synthesis of 192 from methoxybenzene by way of the Birch reduction product 193 is straightforward. Another synthesis of 191 (free acid) is outlined in... 

The recognition of consonant bifunctional relationships in the target molecule allows their disconnection by a retro-Claisen, a retro-aldol or a retro-Mannich condensation or by retro-Michael addition [equivalent, according to Corey s formalisation, to the application of the corresponding transforms (= operators) to the appropriate retrons]. 

Bifunctional systems In the case of bifunctional systems (or molecules) only two alternatives are possible the bifunctional relationships are either "consonant" or "dissonant" (apart from molecules or systems with functional groups of type A to which we have referred to as "assonant"). In the first case, the synthetic problem will have been solved, in principle, in applying the "heuristic principle" HP-2 that is to say, the molecule will be disconnected according to a retro-Claisen, a retro-aldol or a retro-Mannich condensation, or a retro-Michael addition, proceeding if necessary by a prior adjustment of the heteroatom oxidation level (FGI). 

The first two FGIs interconvert two amino groups into their precursors in TM 2.18a next FGA introduces the double C=C bond in TM 2.18b, enabling retro-aldol disconnection of nitromethane and TM 2.18c. Cyano-aldehyde TM 2.18c affords acrylonitrile and stabilized carbanion of isobutyraldehyde on rc/ro-Michael disconnection. 

Convenient disconnection of the 1,5-dicarbonyl pattern results in the a,p unsaturated compound, enone, with a highly reactive C=C bond. Partners in the synthesis are neutral enone and a-carbanion of the second carbonylic reagent to complete the well-known Michael addition [22, 23]. Hence, the disconnection of the central bond in the 1,5-dicarbonyl pattern is denoted as the retro-Michael. 

First we observe that TM 4.9 comprises a 1,5-dicarbonyl pattern and select two central C-C bonds for disconnection (Scheme 4.29). According to route (a), the first retrosynthetic step, refro-Michael disconnection, affords an acetonide anion and target molecule of the second generation, building block TM 4.9a. In the second step, retro-a Ao disconnection of TM 4.9a affords two easily available reagents, benzaldehyde and ethyl cyanoacetate. 

The Robinson annulation combines Michael addition to an a,/3-unsaturated ketone with intramoleeular aldol condensation (Section 18-11) to afford a cyclohexenone. Retrosynthetic analysis (Section 8-9) of the target molecule leads to the disconnection of two bonds in ring A the carbon-carhon double bond, by a retro-aldol condensation, and a single bond by a retro-Michael addition. The Rohinson annulation for the construction of ring A is closely related to the example in Section 18-11, which condenses 2-methylcyclohexanone with 3-buten-2-one. 

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