Robinson-type annulation

Takaki reports that ketone enolates add to dimethylstyryl sulfonium perchlorate (155) or methyl styryl sulfone (156) in a Robinson-type annulation sequence to afford the corresponding 3-hydroxythiadecalin (157) or 5-dioxide (158), respectively subsequent reductive desulfonation of (158) affords diene (159).131 However, additions to acceptor (155) suffer from competing cyclopropanation which is dependent on the electrophilicity of the carbonyl group and the ring size of the ketone (Scheme 61). As an aside, DeLucchi reports that l,l-bis(benzenesulfonyl)ethylene (160) adds to ketones at the more substituted a-carbon under neutral conditions in refluxing acetonitrile (equation 18).132... 

Studies directed at a synthesis of the morphine alkaloids. Regiocontrol in Robinson-type annulations of 2-(hydroxymethyl)-4-oxo-3-piperidinecarboxylic acid. gamma.-lactones Schultz, Arthur G. Shannon, Paul J. 

TMG (1) is used favourably for tandem reactions of Michael and aldol additions [93,94] (Scheme 4.37). Bicyclic furanopyran [93a] and a nucleotide derivative [93b] were synthesized from the corresponding a,p-unsaturated systems in one-pot reaction. A [3.3.1]bicyclic ring system, leading to huperzine A [94a], a candidate drug for Alzheimer decease, and its spirocyclopropyl derivative [94b], is efficiently constructed by Robinson-type annulation from (3-keto ester and methacrolein in the presence of TMG (1) [94] (Scheme 4.37c). 

There is also one example in which a chiral phosphoric acid has been employed as catalyst in the reaction. In particular, the addition of several cyclic p-ketoesters to methyl vinyl ketone was found to occur smoothly in the presence of several chiral phosphoric acids (Scheme 4.35). As mentioned earlier, a key feature of the chiral phosphoric acid catalyst is the backbone binaphthyl axial chirality together with the incorporation of bulky substituents at the 2 positions. In this case, 60b was identified as an appropriate promoter of the reaction leading to the corresponding Michael adducts in excellent yields, although with moderate enantioselectivity. In addition, the authors succeeded in applying this reaction to a procedure to carry out a subsequent Robinson-type annulation. 

Anilide 2a catalysed asymmetric intramolecular Michael reaction of formyl enones to chiral cyclic keto-aldehydes in excellent yields with good stereoselectivity (eqn. (1) in Scheme 6.3). The intramolecular Michael addition of a ketosulfone to an unsaturated ketone (eqn. (2) in Scheme 6.3) catalysed by 15e has heen used as a key step in the synthesis of the carbon tricyclic framework of Lycopodine. The same sulfonylprolinamide served as catalyst in the construction of all-carhon substituted quaternary stereocentre via Robinson-type annulation process (eqn. (3) in Scheme 6.3). 

Dyker, G., Grundt, R, Markwitz, H. and Henkel, G. (1998) Heck reaction and Robinson-type annulation a versatile combination. J. Org. Chem., 63, 6043-7. 

Figure 3.3 The 3D structures of TS3 and TS4. (From Yamanaka, M. et al. Kinetic Resolution in Chiral Phosphoric Acid Catalyzed Aldol Reactions Enantioselective Robinson-Type Annulation Reactions. Eur. J. Org. Ghent. 2012. 24, 4508-4514. Copyright Wiley-VCH Verlag GmbH Co. KGaA. Adapted with permission.)...

Analogously to these examples, proline-derived peptide catalysts can also efficiently promote Michael addition reactions [97-99]. Prolinamide or prolyl sulfonamide catalysts are also effective for intramolecular Michael addition reactions [100-102]. Recently, Yang and Carter reported a short-cut strategy to construct an all-carbon substituted quaternary carbon stereogenic center on a cyclohexe-none framework via Robinson-type annulation using the 17-type catalyst (Scheme 1.4) [103]. 

The combinational use of two chiral Bronsted acids was also investigated. In 2009, AMyama and coworkers developed a novel dual catalysis strategy for the enantioselective two-step Robinson-type annulation reaction in the presence of two different chiral Bronsted acid catalysts (Scheme 43.2) [11]. In the first step, a chiral... 

Scheme 43.2 Enantioselective Robinson-type annulation catalyzed by chiral phosphoric acids.

Example 3, Double Robinson-type cyclopentene annulation... 

Inspired by the proline-catalyzed Robinson annulation pioneered by Wiechert, Hajos, Parrish and coworkers [39], they were able to construct cyclohexanones of type 2-107 with up to four stereogenic centers with excellent enantio- and di-astereoselectivity from unsaturated ketones 2-104 and acyclic (l-ketoesters 2-105 in the presence of 10 mol% phenylalanine-derived imidazohdine catalyst 2-106. The final products can easily be converted into useful cyclohexanediols, as well as y- and e-lactones. 

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. ... 

Dommo-type reactions involve careful design of a multistep reaction in a one-pot sequence in which the first step creates the functionality to trigger the second reaction and so on, making this approach economical and environmentally friendly. A classical example of a tandem reaction is the Robinson annulation (a Michael reaction followed by aldol condensation and dehydration). 

A range of tetrahydro-9f/-xanthen-9-ones arise from photo-induced C-O bond formation of 2-methoxyaryl 2-chlorocyclohex-l-enyl ketones and related compounds (14CC5254). Some examples of tetrahydro-9ff-xanthen-9-ones were obtained as diastereomeric mixtures of cis- and traws-isomers through a 4-DMAP-mediated tandem addition reaction of l-(2-hydroxyaryl)alkynones bearing an aldehyde function (Scheme 76) (140L1642). A Robinson annulation of a P-keto ester and methyl vinyl ketone mediated by tin(lV) chloride afforded a tetrahydro-9H-xanthen-9-one-l-carboxylic acid-type compound (14JOC10689). 

The entire manifold of aldol-type condensation reactions. The aldol condensation itself (Equation 9.45, el seq) and all of those in Table 9.5 (viz. the Claisen, Stobbe, Perkin, and Knovenagel condensation reactions and the Robinson annulation). 

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