Reactions annulation

Seven procedures descnbe preparation of important synthesis intermediates A two-step procedure gives 2-(HYDROXYMETHYL)ALLYLTRIMETH-YLSILANE, a versatile bifunctional reagent As the acetate, it can be converted to a tnmethylenemethane-palladium complex (in situ) which undergoes [3 -(- 2] annulation reactions with electron-deficient alkenes A preparation of halide-free METHYLLITHIUM is included because the presence of lithium halide in the reagent sometimes complicates the analysis and use of methyllithium Commercial samples invariably contain a full molar equivalent of bromide or iodide AZLLENE IS a fundamental compound in organic chemistry, the preparation... 

In addition to the synthesis of heterocycles, the Corey-Chaykovsky reaction bestows an entry to carbocycles as well. The reaction of (trialkylsilyl)vinylketene 89 with substituted ylide 90 led exclusively to rrans-4,5-dimethyl cyclopentenone 91. The substituted ylide 90 here serves as a nucleophilic carbenoid reagent in the formal [4 +1] annulation reaction. 

The key step of an interesting synthesis of Sempervirine (327) is a triazine Diels-Alder annulation reaction with an enamine (88T3195). 1-... 

The best method to achieve a high regioselectivity is the use of preformed enolates. A double annulation reaction is possible if, for example, a diketone such as 11 is used as starting material. The product of the Michael addition 12 can undergo two subsequent aldol condensation reactions to yield the tricyclic dienone 13 ... 

Davis and co-workers have carried out the first examples of the Knoevenagel condensation and Robinson annulation reactions [61] in the ionic liquid [HMIM][PFg] (HMIM = l-hexyl-3-methylimidazolium) (Scheme 5.1-33). The Knoevenagel condensation involved the treatment of propane-1,3-dinitrile with a base (glycine) to generate an anion. This anion added to benzaldehyde and, after loss of a water molecule, gave l,l-dicyano-2-phenylethene. The product was separated from the ionic liquid by extraction with toluene. 

Carbonyl condensation reactions are perhaps the most versatile methods available for synthesizing complex molecules. By putting a few fundamental reactions together in the proper sequence, some remarkably useful transformations can be carried out. One such example is the Robinson annulation reaction for tire synthesis of polycyclic molecules. The word annulation comes from the Latin annulus, meaning "ring," so an annulation reaction builds a new ring onto a molecule. 

Figure 23.9 This Robinson annulation reaction is used in the commercial synthesis of the steroid hormone estrone. The nucleophilic donor is a /3-diketone.

Problem 23.21 What product would you expect from a Robinson annulation reaction of 2-methyl-1,3-cyclopentanedioiie with 3-buten-2-one ... 

Problem 23.22 How would you prepare the following compound using a Robinson annulation reaction between a jS-diketone and an, /3-unsaturated ketone Draw the structures of both reactants and the intermediate Michael addition product. 

The following molecule was formed by a Robinson annulation reaction. What reactants were used ... 

Robinson annulation reaction (Section 23.12) A synthesis of cyclohexenones by sequential Michael reaction and intramolecular aldol reaction. 

Michael reaction, 894-895 acceptors in, 895 donors in, 895 mechanism of. 894-895 Robinson annulation reactions and, 899-900... 

Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1 and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3 is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl vinyl ketone. This compound generates methyl vinyl ketone in situ by (3-eliminalion. The original conditions developed for the Robinson annulation reaction are such that the ketone enolate composition is under thermodynamic control. This usually results in the formation of product from the more stable enolate, as in Entry 3. The C(l) enolate is preferred because of the conjugation with the aromatic ring. For monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted position in hydroxylic solvents. The alternative regiochemistry can be achieved by using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-substituted enamine is favored, so addition occurs at the less-substituted position. 

Methyl 1-phenylthiovinyl ketones can also be used as enones in kinetically controlled Robinson annulation reactions, as illustrated by Entry 6. Entry 7 shows a annulation using silyl enol ether as the enolate equivalent. These reactions are called Mukaiyama-Michael reactions (see Section 2.6.3). 

As already discussed for aldol and Robinson annulation reactions, proline is also a catalyst for enantioselective Mannich reactions. Proline effectively catalyzes the reactions of aldehydes such as 3-methylbutanal and hexanal with /V-arylimines of ethyl glyoxalate.196 These reactions show 2,3-syn selectivity, although the products with small alkyl groups tend to isomerize to the anti isomer. 

An alternate means of forming 96 arises from reaction of imine 97 with methylvinylketone in a variant of the Robinson annulation reaction. This... 

A procedure using a phase-transfer catalyst is employed to prevent the rapid polymerisation of crotonaldehyde dining the Robinson annulation reaction. 

Scheme 3.31. Intramolecular [4+1] and [4+2] annulation reactions employing domino...

A combination of a Diels-Alder and a Fisher carbene-cyclopentannulation is described as the last example in this subgroup. Thus, Barluenga and coworkers used a [4+2] cycloaddition of 2-amino-l,3-butadienes 4-115 with a Fischer alkoxy-arylalky-nylcarbene complex 4-116 this is followed by a cyclopenta-annulation reaction with the aromatic ring in 4-116 to give 4-117 (Scheme 4.25) [36]. An extension of this domino process is the reaction of 4-118 with 2equiv. of the alkynyl carbene 4-119 containing an additional C-C-double bond (Table 4.2) [37]. The final product 4-120, which was obtained in high yield, is formed by a second [4+2] cycloaddition of the primarily obtained cyclopenta-annulated intermediate. 

A first example of a combination of a Rh-catalyzed allylic substitution and a Pau-son-Khand annulation reaction has also been developed by the same group [222]. Thus, [RhCl(CO)dppp]2 is able to catalyze both transformations at different reaction temperatures. Treatment of the allylic carbonate 6-106 with the alkyne derivative 6-107 led to a diastereomeric mixture of 6-108 and 6-109 in 63-84% yield, with 6-108 as the main product (Scheme 6/2.23). 

Other annulation reactions using TiIV-based Lewis acids have been also reported (Scheme 27) 1,3-dipolar cycloadditions,100 [2 + 2] cycloadditions,101 the ene reaction,102 and [3 + 4] cycloadditions103 are also promoted by Tilv compounds. 

We attempted the key intramolecular oxa-[3 + 3] annulation reaction of diketo-enal 8 under high-dilution conditions at room temperature using piperidinium acetate salt in THF. We were delighted upon the discovery of the formation of the desired... 

One-pot syntheses of diaryl-a-tetralones by Michael condensation and subsequent Robinson annulation reactions of isophorone with chalcones were performed efficiently in a solvent-free PTC system under the action of MW irradiation. Compared with conventional heating substantial rate enhancements were observed, within very short reaction times, by use of microwaves (Eq. 59 and Tab. 5.31). They were far better than those achieved by the classical method (NaOEt in EtOH under reflux for 24 h 40-56%). 

Annulation reaction of (benzotriazol-l-yl)acetone 531 with chalcones provides an efficient route to 3,5-diarylphenols 538. The reaction is catalyzed by NaOH in ethanol. In the first step, Michael addition of ketone 531 to the C=C bond of a chalcone gives diketone 532. In the second step, condensation between the carbonyl... 

The annulation reaction of thioamides with 2-alkynoates and 2,3-dienoates under the catalysis of phosphine provides 4,5-dihydro-1,3-thiazoles, particularly those with 2-aryl substituents (Scheme 14).35... 

Smith and co-workers have recently expanded the scope of the [4+1] radical annulation reaction between isonitriles and 1-iodoalkynes to include vinylisonitriles <00JCS(P1)641>. Thus, vinylisonitrile 17 and iodide 18 afford annulated pyridine 19. 

Aniinophenyl)-a,(J>-ynones react with nitrile oxides by domino [3 + 2] cycloaddition/annulation reactions, giving rise to isoxazolo[4,5-c]quinolines in satisfactory yields (434). Nitrile oxides undergo addition to allylzinc bromide to generate 5-butenylisoxazolines in good yields. The domino reaction combines 1,3-cycloaddition with Wurtz coupling (435). 

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