Alcohol Robinson annulation

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

A bis-annulated carbohydrate has been reported by Pipelier and Ermolenko [368] in their synthetic route to quadrone. This complex stmcture was elaborated from levoglucosan by two successive branchings of allyl groups at C2 and C4 using epoxide opening methodology. A keto group, formed from the alcohol at C3, allowed initial cyclopentenone constmction. Further manipulation of this ketone allowed a second Robinson annulation to form the second fused six-membered carbocycle. 

The Robinson annulation has three distinct steps the Michael addition of the enol or enolate across the double bond of the a,(3-unsaturated ketone to produce a 1,5-diketone (Michael adduct), followed by an intramolecular aldol reaction, which affords a cyclic (3-hydroxy ketone (keto alcohol), and finally a base-catalyzed dehydration which gives rise to the substituted cyclohexenone. An alternative mechanism via disrotatory electrocyclic ring closure is possible. ... 

Robinson annulation although not extensively has been used in synthetic routes toward complex carbohydrate structures such as in the synthesis of 82. The starting ketone 80 reacts with (trimethylsilyl)but-3-en-2-one at -78 °C in the presence of lithium 2,2,6,6-tetramethylpiperidide (LTMP) base to give the alcohol 81. The a-methyl inverts to the axial position. The alcohol then produces the Robinson annulation adduct 82 in the presence of catalytic amount of methanolic potassium hydroxide in 58% yield. 

The alcohol adducts from Q -(trimethylsilyl)vinyllithium and aldehydes have found many uses in organic synthesis. The ketones obtained by oxidation (eq 4) are especially good Michael acceptors and have been used in a modified Robinson annulation reaction for the construction of cyclohexenones. Cyclopropana-tion leads to cyclopropylsilane adducts, which can be converted into a variety of cyclopentenes (eq 5). Halogenation followed by stannylation gives synthons (eq 6) useful for making substituted vinylsilanes through radical reactions. ... 

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