Ketones, methyl vinyl intermolecular

Trost et alJ2 also explored the compatibility of di-, tri-, and tetrasubstituted allenes with their intermolecular Alder-ene protocol. Multiple substituents present the opportunity for a mixture of products to arise from differing regio- and chemoselectivity. 1,1-Disubstituted allenes were coupled to methyl vinyl ketone with excellent chemo-selectivity only when one set of /3-hydrogens was activated by an cy-ester or amide (Equation (69)). If the /3-hydrogens were of similar acidity, a mixture of products was obtained, as in the coupling of allenol 103 with methyl vinyl ketone dienes 104 and 105 are produced in a 1.3 1 mixture (Equation (70)). 

Scheme 22.8 Use of methyl vinyl ketone (MVK) in intermolecular hydrogen-mediated reductive aldol coupling.a)...

Elsewhere, Heaney et al. (313-315) found that alkenyloximes (e.g., 285), may react in a number of ways including formation of cyclic nitrones by the 1,3-APT reaction (Scheme 1.60). The benzodiazepinone nitrones (286) formed by the intramolecular 1,3-APT will undergo an intermolecular dipolar cycloaddition reaction with an external dipolarophile to afford five,seven,six-membered tricyclic adducts (287). Alternatively, the oximes may equilibrate to the corresponding N—H nitrones (288) and undergo intramolecular cycloaddition with the alkenyl function to afford five,six,six-membered tricyclic isoxazolidine adducts (289, R = H see also Section 1.11.2). In the presence of an electron-deficient alkene such as methyl vinyl ketone, the nitrogen of oxime 285 may be alkylated via the acyclic version of the 1,3-APT reaction and thus afford the N-alkylated nitrone 290 and the corresponding adduct 291. In more recent work, they prepared the related pyrimidodiazepine N-oxides by oxime-alkene cyclization for subsequent cycloaddition reactions (316). Related nitrones have been prepared by a number of workers by the more familiar route of condensation with alkylhydroxylamines (Scheme 1.67, Section 1.11.3). 

Unsymmetrical dipolarophiles were found to undergo intermolecular cycloaddition with isomiinchnones with high regioselectivity [27]. For example, the decomposition of diazoimide 9 with Rh2(OAc)4 in the presence of methyl vinyl ketone resulted in the formation of two products identified as 27 and 28 in 27 %... 

This procedure illustrates a general method for preparing a wide range of spirocyclohexenones and hence spirocyclohexadienones. A number of intramolecular and intermolecular reactions are known to give spirodi-enones however, these methods have limited synthetic application.2 This procedure is superior3 to that developed by Bordwell and Wellman,4 for side reactions such as aldol condensation of the aldehyde and polymerization of methyl vinyl ketone are avoided. These spirodienones are useful intermediates in the synthesis of paracyclophanes.5 6... 

Thus, treatment of phenol 318 with catalytic amounts of Pd(tfa)j and (S,S)-Bn-BOXAX (310) led again to a Wacker oxidation, which was followed by an intermolecular Heck reaction with methyl vinyl ketone 319 to yield chromane 320. This could then be converted into a-tocopherol (177). The conversion of 318 to 320... 

Methyl vinyl ketone (195) underwent Heck reaction with cyclic iodonium salt 196 in the presence of Pd(OAc)2 and proton sponge to give binaphthyl iodide 197 in 81% yield (Scheme 22.45) [68]. When the base was switched from proton sponge to EtsN, annulated product 198 was produced in 88% yield the conditions smoothly catalyzed not only the intermolecular Heck reaction but also intramolecular Heck reaction of 197. It is noteworthy that 196 is utilized as a synthetic equivalent of 2,2 -diiodobinaphthyl. 

A few examples of the intermolecular reductive process have been reported in natural product synthesis. A total synthesis of the antimalarial drug (+)-artemismin, a sesquiterpene endoperoxide, was achieved via an intermolecular reductive radical reaction (Scheme 25.20)." lodolactone 44 was treated with methyl vinyl ketone (MVK) using TTMSS as a chain carrier and reductive reagent to provide... 

There is only one example in the literature where an enyne RCM coupled to an intermolecular CM in a sequence process has been applied in the synthesis of a natural product. The synthesis of (-i-)-8-epi-xanthatin, isolated from the leaves extracts from Xanthium canadense, was proposed by Martin et al. through an enyne RCM-CM cascade combining ring closing of 8 with a CM with 9 [13]. The special challenge for this transformation consists in the use of an electron-poor olefin for the final metathesis reaction. The use of [Ruj-III (20mol%), the catalyst of choice for this type of transformations [14], and an excess (10 equiv.) of the methyl vinyl ketone 9 resulted in the formation of the desired product in 83% yield (Scheme 11.3). 

This reaction was first reported by Nenitzescu in 1931. It is the formation of an a,p-unsaturated ketone directly by aluminum chloride-promoted acylation of alkenes with acyl halides. Therefore, it is known as the Darzens-Nenitzescu reaction (or Nenitzescu reductive acylation), or Nenitzescu acylation. Under such reaction conditions, Nenitzescu prepared 2-butenyl methyl ketone from acetyl chloride and 1-butene and dimethylacetylcyclohex-ene from acetyl chloride and cyclooctene. However, in the presence of benzene or hexane, the saturated ketones are often resolved, as supported by the preparation of 4-phenyl cyclohexyl methyl ketone from the reaction of cyclohexene and acetyl chloride in benzene, and the synthesis of 3- or 4-methylcyclohexyl methyl ketone by refluxing the mixture of cycloheptene and acetyl chloride in cyclohexane or isopentane. This is probably caused by the intermolecular hydrogen transfer from the solvent. In addition, owing to its intrinsic strain, cyclopropyl group reacts in a manner similar to an oleflnic functionality so that it can be readily acylated. It should be pointed out that under various reaction conditions, the Darzens-Nenitzescu reaction is often complicated by the formation of -halo ketones, 3,)/-enones, or /3-acyloxy ketones. This complication can be overcome by an aluminum chloride-promoted acylation with vinyl mercuric chloride, resulting in a high purity of stereochemistry. ... 

Other examples include the free radical polymerization of vinyl isocyanate with subsequent anionic polymerization of the isocyanate side groups, as well as the corresponding polymerization of acrylonitrile or poly(acrylonitrile). Free radical and anionic polymerizations are to be preferred over those initiated by cations, since cationic polymerization frequently tends to give rise to transfer reactions which interrupt the transannulation. For example, in the cyclization of natural rubber with the aid of concentrated acids or Lewis acids, an average of only three transannular rings is obtained [see Equation (25-9)]. The intermolecular elimination of water from poly(vinyl methyl ketone) only produces single, double, and triple rings ... 

In another example, the aiylation of ketone enolates was achieved indirectly via an intermolecular Heck reaction. In this case, the diastereoselectivity is induced by chelation of a metal-coordinating auxiliary. The inexpensive and commercially available amino alcohol (6()-l-methyl-2-pyrrolidine-methanol was selected as a suitable chiral auxiliary (Scheme 13.47). The prolinol vinyl ether 182 was... 

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