Tandem with vinyl ketone

Fusion of SIX membered nngs by reactnn of cyclanones with vinyl ketones (base or acd catalyzed), a tandem Michael addition aldol condensation... 

The boron enolates (up to 98% ee) were used for further transformation by treatment with electrophiles. The rhodium-catalyzed reaction of B-Ph-9BBN was extended to a new type of catalytic tandem conjugate addition-aldol reaction by combination with vinyl ketones and aldehydes [39]. 

The high diastereoselective synthesis of multifunctionalized 3,4-dihydro-coumarins bearing a quaternary stereocenter was developed through tandem Michael additions of indole and its derivatives (1-methyl, 2-methyl, 4-methoxy, 5-methoxy, 5-bromo, 6-benzyloxy) to 3-nitrocoumarines (3-nitro-chromen-2-one, 6- and 7-methyl-3-nitro-chromen-2-one) followed by methyl vinyl ketone in a one-pot step. For the tandem Michael additions, after the first Michael reaction of indole (2) with 3-nitrocoumarine (51) catalyzed... 

The 1,2-thiaphospholes (20) react thermally with norbornadiene, norbornene, or diethyl azo-dicarboxylate to produce double Diels Alder cycloadducts (24) and (25). With mixtures of norbornadiene and methyl acrylate or acrylonitrile, crossed double Diels-Alder cycloadducts are obtained. In the presence of AICI3 the 1,2-thiaphospholes (20) react with acrylic esters, acrylonitrile or methyl vinyl ketone to give tandem Diels-Alder/Michael adducts such as (26). The AICI3-promoted reaction of (20) with ethyl propiolate affords with the elimination of a sulfur atom the stable phosphinine (27) (Scheme 4) <94BCJ2785>. 

A tandem sulfide-contraction and Robinson annelation reaction was used for the synthesis of a me-sembrine analog, A -mesembrenone (133). The aryl-substituted thiobutyrolactam (130) was treated with chloromethyl vinyl ketone followed by diisopropylethylamine to afford A -mesembrenone (133) in good yield (Scheme 29). The reaction probably proceeds through initial sulfide contraction to the intermediate vinyl enaminone (131), which tautomerized to the enamine (132) and underwent intramolecular Michael closure to produce (133). 

Many Lewis bases have been used in this kind of reactions, with perhaps DABCO " being the most employed. Recently, DMAP has proven to be superior to DABCO in reactions such as hydro>ymethylation of cyclohexenones or reactions of aryl aldehydes with methyl vinyl ketone. DBU and TMG have proved to be excellent catalysts for this kind of reaction. DBU catalyses the reaction of salicylaldehydes with allenes to form 2H-l-chromenes. ° Recently, important advances have been made into abnormal MBH reactions, including double-MBH reactions, abnormal aza-MBH reactions and tandem MBH pathways, with DABCO and DMAP being the amine catalysts of choice. ... 

Most of the currently applied protocols for rhodium-catalyzed conjugate addition chemistry involve the use of aqueous solvent systems which ensure catalytic turnover by protonation of the intermediate rhodium enolate. Consequently, tandem reaction sequences with electrophiles other than a proton are troublesome. In early investigations, Hayashi reported a rhodium/BINAP-catalyzed conjugate addition-aldol reaction under anhydrous conditions by use of 9-aryl-9-borabicyclo[3.3.1]no nanes (9-Ar-9-BBN) as aryl sources [117]. The reaction between tert-butyl vinyl ketone (145) with 9-(4-fluorophenyl)-9-BBN (146) and propionaldehyde (147) led to the formation of a syn/anti-mixiuve of 148 in a 0.8 to 1 ratio (Scheme 8.39). 

Disubstituted isocoumarins arise from the copper(II)-catalyzed addition of o-halobenzoic acids to active internal alkynes (13JOC1660), rhodium(III)-mediated oxidative coupling ofbenzoic acids with disubsti-tuted alkynes (13T4454), palladium(II)-catalyzed tandem annulation reaction of o-alkynylbenzoates with methyl vinyl ketone (13T8626), and nickel(II)-promoted t-butyl isocyanide insertion in 2-(o-bromophenyl)-1-ethanones followed by hydrolysis (Scheme 69) (13SC3262). 

Even [3-1-2] cycloadditions occur when cyclopropyl ketones are treated with (1) under photolytic or Lewis acid conditions to produce cyclopentane systems. Cyclopropanations of (1) are well known, in all cases adding to the more electron-rich sUy-loxy alkene. The vinylcyclopropanol silyl ethers can be converted into a number of different products, e.g. cyclopentanones, 2-methylcyclobutanones, vinyl ketones, and -alkoxy ketones (eq 10). One clever use of (1) in synthesis is the tandem [2 + 21-Cope process which converts (34) into (35) (eq 11). ... 

Ring-closing enyne metathesis of 159 generated an intermediate ruthenium carbene which participated in a subsequent cross-metathesis reaction with methyl vinyl ketone to generate the seven-membered carbocycle and ( )-conjugated dienone subunit 162 in a single synthetic transformation. Specifically, treatment of enyne 159 with methyl vinyl ketone 160 in the presence of catalyst 162 (20mol%) provided (+)-8-epi-Xanthatin in 83% yield. It should be noted that the phosphine-free ruthenium catalyst 162 was employed in this step because it had been reported to be superior as a catalyst in tandem RCM-CM reactions reported previously. 

In 2008, Chi et al. reported a tandem reaction of indoles, a,P-unsaturated aldehydes, and methyl vinyl ketone (MVK) for the synthesis of chiral indole derivatives with two stereogenic centers [ 19]. To avoid the interference of the two secondary amine catalysts and cocatalyst acid, the soluble star polymer-based site isolatbn method was adopted, whereby the supported imidazolidinone catalyst promoted initial Friedel-Crafts alkylation and the supported pyrrolidine derivative promoted the following Michael addition to MVK (Scheme 9.19). Notably, simple combination of these catalysts in one pot didn t mediate the cascade reaction efficiently despite the fact that the MacMillan imidazolidinone and pyrrolidine catalyst can efficiently promote separate Friedel-Crafts reaction and Michael addition, respectively. Moreover, when the pyrrolidine catalyst was replaced by its enantiomer, a diaste-reomer of the product could be obtained with high enantioselectivity. This smdy presented a novel solution to the efficient combination of incompatible substrates and catalysts. 

The addition of other deprotonated nucleophiles to vinyl ketone was further expanded recently to the synthesis of much more complex molecules. In 2006, the group led by Shibasaki reported on the concise synthesis of cylindricine C, a spirocychc molecule with numerous biological properties isolated from Clavelina cylindrical (Scheme 11.44). Glycine Schiff base 182 was found to react efficiently with enone 183. Catalyst 184 was the most effective for this transformation giving a good 82% ee at —40°C. Noteworthy, the process tolerated numerous functional groups such as the more substituted enone that was kept untouched. Remarkably, compound 185 could be transformed into the tricychc backbone 186 of cylindricine C by a tandem cych-zation in acidic conditions. 

Tandem Carbon-Carbon Bond Formation via Brook Rearrangement Takeda et al. have reported that the reactions of benzoyl- and crotonylsilanes with hthium enolates of methyl ketones produce 1,2-cyclopropanediol monosilyl ethers via the Brook rearrangement of the initial 1,2-adduct 158 and the subsequent internal nucleophilic addition (Scheme 10.225) [587]. No formation of the corresponding cyclopropanes with alkanoylsilanes implies fhat fhe Brook rearrangement is accelerated by the phenyl or vinyl group. 

Though dramatic, this is an unusual example of such processes. Much more has been made of tandem aza-Cope and Mannich reactions, particularly by Overman. A typical sequence begins with the addition of a vinyl-lithium, e.g. 176, to a protected a-aminoketone 177 to give, in this case, the product 178 from Felkin-like attack (chapter 21) on the side of the ketone anti to the amino group.27... 

Vinyl esters are silylated at the trigonal a-carbon, making available the enol esters of silyl ketones. The regioselective deprotonation of )3-alkoxyacrylic esters and the ability of the lithio derivative to undergo a tandem Michael-Julia condensation with suitable acceptors are exploitable in the synthesis of highly functionalized cyclopentenones. ... 

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