Retro Michael cleavage

The stereochemical course of the subsequent Michael addition of malonic ester to the unsaturated ketone (23) proved to be unexpected. The kinetically controlled product 27 of addition was obtained in the presence of sodium methoxide and an excess of dimethyl malonate however, the thermodynamically preferred ester 28, also obtainable by base-catalyzed equilibration of 27, was the major product of the reaction. According to the IR (absence of Bohlmann bands) and NMR spectra, both 27 and 28 contained cis-quinolizidine ring systems formed possibly by reversible retro-Michael cleavage of the C-3 to Aj, bond in 23. This possibility explains the observed rapid destruction of 23 in the presence of very strong base with simultaneous appearance of a UV maximum at 410 nm presufiaably due to the conjugated enone system present in 29. 

Raney nickel, 13, 54, 76, 109, 119, 172, 337,401,502-503, 651,667 Reductive acetylation, 4 Reductive methylation, 528 Reformatsky reaction, 293, 674-675 Retro Diels-Aldet reaction, 379 Retro Michael cleavage, 284 Rhodium on alumina, 503 Rhodium on carbon, 503 Rhodium carbonyl, 504 Rhodium trichloride Silica, 504 Rhodium trichloride hydrate, 504 Ring expansion, 162-163, 194, 252-253,... 

The retrosynthesis involves the following transformations i) isomerisation of the endocyclic doble bond to the exo position ii) substitution of the terminal methylene group by a more stable carbonyl group (retro-Wittig reaction) iii) nucleophilic retro-Michael addition iv) reductive allylic rearrangement v) dealkylation of tertiary alcohol vi) homolytic cleavage and functionalisation vii) dehydroiodination viii) conversion of ethynyl ketone to carboxylic acid derivative ix) homolytic cleavage and functionalisation x) 3-bromo-debutylation xi) conversion of vinyl trimethylstannane to methyl 2-oxocyclopentanecarboxylate (67). 

Compounds in which two donor atoms are linked by a three-carbon chain undergo C-C bond cleavage readily. Well-known reactions are the retro-aldolization, retro Claisen, retro-Michael, and retro-Mannich reactions. Significant application of such processes to synthesis of complex natural products include approaches to caryophyllene [80], nootkatone [81], trihydroxydecipiadiene [82], hybridalactone [83], and mesembrine [84],... 

Sulfur has been used in linkers such as thioethers, sulfoxides, sulfones, sulfonic acids and their corresponding derivatives. A safety-catch linker for amines is based on 2-(thiobenzyl)ethylcarbamates [44]. Linkage is performed with preformed handles containing ethenyloxycarbonyl-protected amines 37. Attachment to thiomethyl-ated polystyrene 38 is performed under conditions involving radicals. Cleavage was performed with an oxidizing agent, which forms the retro Michael substrate (Scheme 6.1.11). 

The acid-catalyzed fission of macralstonidine can then be explained by the reversal of these processes, i.e., as a combination of retro Michael and retro aldol cleavages on the phenolic hydroxyketone LVII (35). 

It should be noted that cleavage of the C -Cp bond of the alkyl cyanide 110 to the nitrile 111 has been reported (Scheme 6.25) [81]. This transformation is a formal retro-Michael-type fragmentation, but proceeds under neutral conditions. Oxidative addition of an a-C-H bond followed by P-carbon elimination is suggested. 

The presence of the ortho-riiXro group allowed nucleophilic cleavage to liberate the desired amine [6]. An amidine linker [7,8] provided a resin bound amine that was stable to oxidative, reductive, and alkylative conditions. The use of 2-chlorotrityl resin proved to be useful for the preparation of a secondary amine library [9] as well as hydroxamic acids [10]. Tertiary amines were prepared by 1,4 addition to a resin bound acrylate followed quatemization and a retro-Michael reaction [11]. The p-nitrophenyl carbonate linker has been shown to be useful for the inunobilization of ben-zamidines [12] and for the synthesis of sulfonamides [13]. Sulfonamides and amides were also prepared using a halogenated Wang resin [14]. 

Knoevenagel adduct 239 of oxohomophthalimide 240 with malononitrile 27a in reactions with CH-acids behaves ambiguously (82CPB1215). Reactions of 239 with acetylacetone, ethyl esters of acetoacetic and ben-zoylacetic acids, as well as methyl pyruvate led to the formation of the desired spiropyrans 241. However, benzoylacetone, dibenzoylmethane, cyanacetamide, and oxindole always gave the same 242. Authors explain this feature in terms of a retro-cleavage of adducts of Michael product 239... 

A short and highly diastereoselective synthesis of tetrahydropyran-4-ones was recently reported hy the group of Tong. Reductive 1,2-oxazoline N-O cleavage in 71 with Sml2 followed by acid-catalysed 6-e do-trig oxa-Michael cyclisation of the crude product furnished q n-tetrahydropyran-4-one 72 (Scheme 25). Extended reaction times resulted in improved yields and diastereoselectivities, presumably due to a retro-oxa-Michael/ oxa-Michael isomerisation. The total synthesis of ( )-diospongin Awas completed in a 20% overall yield. 

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