Intramolecular effects fluoride

Some examples of conjugate addition reactions of allylic silanes are given in Scheme 9.5. Entries 1 to 3 illustrate the synthesis of several (3-allyl ketones. Note that Entry 2 involves the creation of a quaternary carbon. Entry 4 was used in the synthesis of a terpenoid ketone, (+)-nootkatone. Entry 5 illustrates fluoride-mediated addition using tetrabutylammonium fluoride. These conditions were found to be especially effective for unsaturated esters. In Entry 6, the addition is from the convex face of the ring system. Entry 7 illustrates a ring closure by intramolecular conjugate addition. 

Intramolecular conjugate allylation (12, 25).2 Fluoride ion catalyzes intramolecular Michael additions of allyltrimethylsilane to a,p-enones as well as a,p-unsaturated esters, nitriles, and amides Lewis acid catalysis is not effective. The method is particularly suited to cyclopentane annelations.2... 

Intramolecular substitution for chloride or fluoride is particularly effective. Oxygen heterocycles with fused benzo rings are obtained from Cr(CO>3 complexes of fluorobenzene with an o-(hydroxyalkyl) side chain.39,60 For example, complexation of 3-(2-fluorophenyl)-l -propanol with [Cr(CO>3(pyridine)3] at 25 C in ether (promoted by BF3 Et20) followed by reaction in DMSO with excess potassium f-butoxide for 3 h at 25 C gave the chroman complex (14).60 The yield in the cyclization step was 75% and iodine decomplexation was quantitative (equation 12). Efforts to produce the dihydrobenzofuran under the same... 

Probably the two most generally useful methods for effecting intramolecular acylation are by the Friedel-Crafts type of reaction on the acid chloride and the action of anhydrous hydrogen fluoride on the free acid. In addition to these methods, cyclizations have been effected by the use of sulfuric acid and other reagents. 

In 1939 it was observed16 that anhydrous liquid hydrogen fluoride is an excellent agent for effecting intramolecular acylation of aryl substituted aliphatic acids. Since that time a number of cyclizations have been performed with this reagent (Table VIII). 

With water, the reaction was carried out in aqueous acetonitrile at 0°C, but the products (p-quinols) were formed in moderate yield better results were obtained with silylated phenols, especially with their tripropylsilyl ethers [13]. For fluorina-tion, pyridinium polyhydrogen fluoride was the source of fluoride this system was effective with a variety of substrates, including a phenolic steroid [15]. As with DIB, intramolecular cyclizations were also performed on several occasions. 

Another type of intramolecular electrophilic substitution is shown in Equation (1).25 In this case, the reaction sites are located in different substituents on silicon. This reaction mode is useful for highly diastereoselective alkenylation and phenylation of aminoacetals and hemiaminals.26 Intramolecular conjugative arylation of a-enals bearing an aryldimethylsilyl group is effectively promoted by tetrabutylammonium fluoride (TBAF) (Equation (2)).27,27a... 

Cu(II) is intramolecular. The effect of fluoride on the reduction rate is consistent with both a direct involvement of type 2 Cu(II) in the reduction or an indirect effect mediated via a change in conformation or in redox potential of the type 1 Cu(II). The type 2 copper ion could be the primary electron-accepting site of the laccase molecule, as has been proposed for the reduction of the enzyme by hydroquinone (36), the first-order process observed being therefore the electron transfer from type 2 Cu to type 1 Cu(II). The particaption of type 3 Cu(II) instead of type 2 Cu(II) is not excluded, but no associated change of its absorption band at 330 nm could be observed during the redox cycle described for the 614-nm band. 

The hydroxy part of a hydroxy acid can also be activated for macrolactonization. Vedejs et al. [60] applied such a strategy to the synthesis of the macrocychc pyrrolizidine alkaloid monocrotaline 108). Thus, the seco acid derivative 106 was first mesylated with MsCl/EtjN in dichloromethane, and the crude product was added over 3 h to an excess of tetrabutylammonium fluoride trihydrate in acetonitrile at 34 °C to effect ring carboxy deprotection and ring closure to give 107 in 71% yield (Scheme 36). It has been noted that the active intermediate of this kind of lactonization may be an allylic chloride rather than a mesylate [61a], In addition, an intramolecular nucleophilic displacement process of chloride from an a-chloro ketone moiety by a remote carboxylate has been recently reported as an efficient approach to macrocychc keto lactones [61 bj. 

Nitrosoalkenes.1 Nitrosoalkenes are usually generated by reaction of a-halo oximes with bases, and have been used for [4 + 2] cycloadditions. They are also generated efficiently from a-chloro silyloximes by fluoride ion. This elimination is used to effect an intramolecular cyclization of the nitrosoalkene generated from 1 to give a mixture of the dihydrooxazines 2 and 3. The choice of the metal fluoride is critical for acceptable yields. Highest yields are obtained when the nitrosoalkene is generated slowly by a... 

Because electrophilic aromatic substimtions have provided access to C-arylglycosides via intermolecular reactions, similar technology is available for effecting the intramolecular delivery of the aromatic species. For example, utilizing the furanosyl fluoride shown in Scheme 7.27, Araki et al. [115] achieved formation of an 83% yield of the bicyclic product on treatment with borontrifluoride etherate. Similar chemistry is known for methyl glycosides [116,117] and glycosyl acetates [118]. 

Silenes (compounds with an Si=C double bond) are known to be extremely reactive compounds. Till now, only a few silenes, stabilized kinetically by bulky substituents, could be isolated under normal conditions and were characterized by X-ray structural analyses [1]. An effective stabilization of Si=C systems is also achieved by coordination of a base, such as amines, THF, or fluoride ions, to the electrophilic silene silicon atom [2], and recendy we succeeded in synthesizing thermally unexpectedly stable intramolecularly donor-stabilized silenes [3]. In this paper, the synthesis and, in particular, the behavior of the l-[2,6-bis(dimethylaminomethyl)phenyl]silenes 2a-d are described. 

The regioselective effect of the fluoride ion on intramolecular nucleophilic cyclization has also been demonstrated for heptafluoronaphthylsulfur diimide (94HAC561, 92POL1137). The reaction of the latter leads to a mixture of 4,5,6,7,8,9-hexafluoronaphtho[l,2-c][l,2,5]thiadiazole, whose structure was established from X-ray diffraction, and 4,5,6,7,8,9-hexafluoronaphtho-[2,3-c][l,2,5]thiadiazole (in the ratio 94 6) (94HAC561) (Scheme 158). 

A combination of the aryl fluoride approach with the activating effect of the aromatic nitro group was useful in intramolecular... 

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