Cyclic alkenyl ethers

The intramolecular addition of the O-H bond to alkynes catalyzed by palladium complexes has been developed by K. Utimoto et al. (Eq. 6.59) [104]. An alkynyl alcohol can be converted to a cyclic alkenyl ether in the presence of a catalytic amount of [PdCl2(PhCN)2 or [PdCl2(MeCN)2] in ether or THE at room temperature. When the reaction was carried out in MeCN-H20 under reflux in the presence of a catalytic amount of PdCl2, hydration of the acetylenic alcohol occurred and the ketoalcohol was obtained in good yield instead. 

Cyclic alkenyl ethers have been prepared by intramolecular O-vinylation of /3-keto esters using a pendant vinyl bromide, with copper catalysis.208... 

The formation of five-, six-, and seven- membered ring cyclic alkenyl ethers from the intramolecular O-vinylation (.S n2) reactions of vinyl bromides containing a y- or 5-011 or -keto group, has been reported.17 The reactions, which require a Cul catalyst, a diamine, and K2CO3, are complete in a few hours in refluxing THF. 

As an example, formation of cyclic alkenyl ethers 2 and 3 from acetylenic aldehyde 1 is catalyzed by Pd(OAc)2,. Also, 2-alkynylbenzaldehyde 7 was converted to the cyclic alkenyl ether 8 in high yield in the presence of Pd(OAc)2 (5 mol%) in MeOH. In these reactions, Pd(OAc)2 as a Lewis acid, coordinates to the carbonyl group to facilitate the formation of the hemiacetals as shown by 5, Then either 5-exo or 6-endo cyclization (oxypalladation of triple bond) occurs to give 6 or 6a. Finally, protonolysis of 6 and 6a affords the cyclized products 2 and 3 with regeneration of Pd(OAc>2.. In this reaction, Pd(OAc>2 exhibits dual roles [1]. 

Analogous cleavage of a C=C triple bond has been found in the gold-catalyzed cyclization of (Z)-enynol 157 under an oxygen atmosphere (Scheme 7.54) [73]. Butenolide 159 was obtained by way of the cyclic alkenyl ether 158. 

A particular pathway for the synthesis of cyclic alkenyl ethers by intramolecular C-0 bond formation consisted in the reaction of y-acetylenic aldehydes in the... 

Asao N, Nogami T, Takahashi K, Yamamoto Y (2002) Pd(U) Acts simultaneously as a Lewis acid and as a transition-metal catalyst synthesis of cyclic alkenyl ethers liom acetylenic aldehydes. J Am Chem Soc 124 764—765... 

Only a few benzo derivatives are known, and most of them have the oxygen attached to the aromatic rings, i.e. they are cyclic phenol ethers or esters. 3,4,5,6-Tetrahydro-2H-1-benzoxocin (136), mentioned above, can also be obtained by cyclization of o-(bromopentyl)phenol (139) with base. The cyclization is rapid in DMSO and does not require high dilution conditions. The yield of (136) is 30% the alkenyl phenol (140) is obtained in 57% yield (74JOC2598). The latter product is formed by an intramolecular E2 reaction and thus is independent of the concentration of (139). In 75% ethanol solution, more of (136) is formed (64%) and less of (140) (35%), even though the rate of cyclization is much lower than in DMSO (75JA4960). 

Various alkenyl ethers undergo Heck coupling in a basic medium in the presence of a Pd(0) catalyst to form cyclic ethers such as benzofurans and tetrahydroben-zopyrans.1... 

The ring-closing enyne metathesis has been used for the synthesis of alkenyl substituted six- and seven-membered cyclic enol ethers (Eq. 88) [144]. The reaction has been proposed as an element of the strategy for preparation of subunits of brevetoxins and ciguatoxins. 

Cyclic sUyl ethers/ Alkenyl silanols cyclize in the same manner as the all-carbon analogues. 

A variety of NMR spectroscopic methods have been applied to structural and conformational analyses of the following furanose systems sugar em-dimethyl substituted alkenyl ethers, e.g. a-D-xylofuranose derivatives 13 (see Chapter 5 for synthesis), " the diastereomeric 6-chloro-6-deoxy-l,2-0-isopropylidene-a-D-gulofuranose cyclic 3,5-piperididomonophosphates 14, several 4 -thionucleo-sides, 6-formyl- and 6-(hydroxymethyl)-uridine 5 -carboxaldehydes 15 and 16, respectively, and their 2, 3 -0-isopropylidene derivatives, two double-... 

In 1979 Wenkert reported the cross-coupling reaction of alkenyl methyl ethers with phenyl and methyl magnesium halides via the activation of C(sp )-OMe bonds by using NiCl2(PPh3)2 as a catalyst precursor [Eq. (2)] [12, 13]. This alkenyl ether cross-coupling was further extended to silyl enol ethers [14] and cyclic ethers, such as dUiydrofurans [15-23], which offer a unique method for the stereoselective construction of alkenes (see Sect. 4). 

J-Oxygen-functionalised sp3 organolithium compounds react with alkenyl-carbene complexes to generate the corresponding cyclic carbene complexes in a formal [3+3] process (see Sect. 2.8.1). In those cases where the organolithium derivative contains a double bond in an appropriate position, tricyclic ether derivatives are the only products isolated. These compounds derive from an intramolecular cyclopropanation of the corresponding cyclic carbene complex intermediate [89] (Scheme 83). 

This procedure illustrates a general method for the stereoselective synthesis of ( P)-disubstitnted alkenyl alcohols. The reductive elimination of cyclic /3-halo-ethers with metals was first introduced by Paul3 and one example, the conversion of tetrahydrofurfuryl chloride [2-(chloromethyl)tetrahydrofuran] to 4-penten-l-ol, is described in an earlier volume of this series.4 In 1947 Paul and Riobe5 prepared 4-nonen-l-ol by this method, and the general method has subsequently been applied to obtain alkenyl alcohols with other substitution patterns.2,6-8 (I )-4-Hexen-l-ol has been prepared by this method9 and in lower yield by an analogous reaction with 3-bromo-2-methyltetra-hydropyran.10... 

Table 14.2. Preparation of cyclic ethers and sulfides from alkenyl thioacetals. ...

Enantioselective conjugate addition can also be carried out with cyclic enones. Shuichi Oi and Yoshio Inoue of Tohoku University in Sendai report (Tetrahedron Lett. 2004, 45, 5051) that a BINAP complex of Rh catalyzes the enantioselective conjugate addition of alkenyl Zr species such as 5, to give 7 in high enantiomeric excess. Alkenyl Zr species such as 5 are readily prepared by hydridozirconation of alkynes. It is particularly important that addition of TMS-C1 to the reaction mixture at the end of the conjugate addition leads cleanly to the enol ether 6. 

Several alkenyl hydroperoxides have been successfully cyclized to five-, six- and seven-membered ring peroxides (equation 241).38s 388 Alkaline sodium borohydride reduction of these mercurials is frequently accompanied by epoxide or cyclic ether formation. 

The reaction of alkenyl alkyl ethers and ketene acetals with PX3 (X = Cl or Br) has been reported to occur readily in the presence of an organic base and to result in the electrophilic substitution of a vinyl hydrogen atom with the PX2 group. Thus, (2-alkoxyalkenyl)-, (l-bromo-2-alkoxyalkenyl)- and (2,2-dialkoxyalkenyl)-phosphorus dichlorides and dibromides were obtained in 70-98% yield. The reaction proceeds regio- and stereo-selectively and is believed to involve formation of a cyclic phosphirenium ion.74... 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

Electrophilic substitutions of alkenyl-, aryl-, and alkynylsilanes with heteroatom-stabilized cationic carbon species generated by the action of a Lewis or Brpnsted acid (acyl cation, oxocarbenium ion, etc.) provide powerful methods for carbon-carbon bond formation. Particularly, intramolecular reactions of alkenylsilanes with oxocarbenium and iminium ions are very valuable for stereoselective construction of cyclic ether and amine units.21-23 For example, the BFj OEt -promoted reaction of (E)- and (Z)-alkenylsilanes bearing an acetal moiety in the alkenyl ligand gives 2,6-disubstituted dihydropyrans in a stereospecific manner (Scheme l).23 Arylsilanes also can be utilized for a similar cyclization.24... 

Elaboration of isoxazolines has been used in the synthesis of other heterocycles. Electrophilic cyclization reactions of 5-alkenyl-substituted isoxazolines (150) have been used in the synthesis of cyclic ethers (Scheme 68) (87JA7577 90JOC283). Hydrogenolysis and decarboxylation of the... 

Alkenylsilanes and -stannanes, and arylsilanes and -stannanes are useful reagents for transfer of an sp -carbon unit to electrophiles under titanium catalysis. Epoxides are opened by TiCE to generate cationic carbon, which is successfully trapped with bis(trimethylsilyl)propene as an aUcenylsilane (Eq. 122) [305]. Other Lewis acids, for example ZnCla, SnCU, and BF3 OEt2, proved less satisfactory. Cyclic epoxides such as cyclopentene and cyclohexene oxides gave poorer yields. An intramolecular version of this reaction proceeded differently (Eq. 123) [305]. Eqs (124) and (125) illustrate diastereoselective alkenylation and arylation of (A,0)-acetals that take advantage of the intramolecular delivery of alkenyl and aryl groups [306], Cyclic ethers... 

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