Ethers 1-iodoalkyl

Based on a transformation described by Catellani and coworkers [61], the Lautens group [62] developed a three-component domino reaction catalyzed by palladium for the synthesis of benzo annulated oxacycles 6/1-114 (Scheme 6/1.30). As substrates, these authors used a m-iodoaryl iodoalkyl ether 6/1-113, an alkene substi-... 

As a unique [1,4]-Wittig rearrangement, the transformation of 3-iodoalkyl vinyl ether 107 to the 4-alken-l-ol 108 has been reported by Bailey s group (equation 61, Table 5) . The rearrangement is undoubtedly mediated by a regiospecific 5-cxo-trig ring closure. 

Free radical addition to oximes and oxime ethers emerged as a useful alternative to addition of organometallic reagents, particularly for intramolecular reactions. The most important advantage of free radical V5. organometallic addition is its tolerance for almost any functional group (with the exception of thiocarbonyl and iodoalkyl functions). 

When 2-iodoalkyl vinylsilyl ethers 231 (Z=Si) were reacted with 224 in the presence of the Co(dppb)Cl2 catalyst, silatetrahydrofurans 232a (Z=Si) were isolated [294], When substrates 231 with substituted allyl groups (R3 and/or R4=alkyl) were treated with catalytic amounts of Co(dppe)Cl2 and 224 or phenylmagnesium bromide, a 5-exo cyclization proceeded and tetrahydrofurans 232c with exocyclic alkenyl units were isolated in 58-89% yield. For substrates with disubstituted alkene acceptors (R3=alkyl, R4=H), the formation of 18% of reduced tetrahydrofuran 232b was also observed [280, 295],... 

Non-stabilized carbonyl ylides such as 3.55 can be prepared from 1-iodoalkyl triethylsilyl ethers (3.53), probably via bis( 1-iodoalkyl) ethers (3.54). 

Mg turnings which are treated w radicals from iodoacetaldehyde u Other tetrahydrofuran derivative a-iodoalkyl silyl ethers and activi The parent carbonyl ylide is gew system, 3-substituted and 3,4-di ... 

For instance, 1-chloroethyl ethyl ether is obtained from acetaldehyde diethyl acetal and PC15,1057 chlorobenzyl methyl ether from benzaldehyde dimethyl acetal, acetyl chloride and SOCl21058 and 1-bromoalkyl ethers from the corresponding acetals.1059 1-Bromoalkyl ethers can also be prepared from 1-chloroalkyl ethers into which HBr is passed at about 20° 1-iodoalkyl ethers are obtained from the 1-chloro analogs by use of Nal in acetone. 

Cyclic ether cleavage. Sml. is a typical Lewis acid, which induces reaction with acid chlorides. It also contributes an iodide ion, giving ni-iodoalkyl carboxylates. 

Tetrahydrofurans a-Iodoalkyl trialkylsilyl ethers undergo a very unusual reaction with Srnlj in an ethylene atmosphere. 

Fluorinated five- to seven-membered cyclic ethers have been stereoselectively synthesized from iodoalkyl substituted four- to six-membered cyclic ethers by fiuorinative ring-expansion reaction using difluo-roiodotoluene [31]. Scheme 3.10 shows a specific example of a fiuorinative ring-expansion reaction of oxetanes 24 leading to five-membered cyclic ethers 25 [31]. 

A stereoselective synthesis of five- to seven-membered cyclic ethers has been achieved by de-iodonative ring-enlargement of cyclic ethers having an iodoalkyl substituent. For example, the reaction of tetrahydrofuran derivative 360 with (diacetoxyiodo)toluene proceeds under mild conditions to afford ring-expanded product 361 (Scheme 3.144). The use of hexafiuoroisopropanol (HFIP) as solvent in this reaction is critical [462]. 

Based on a transformation described by Catellani and coworkers [80], Lautens s group [81] developed a series of syntheses of carbocycles and heterocycles from aryl iodide, alkyl halides and Mizoroki-Heck acceptors. In an early example, the authors described a three-component domino reaction catalysed by palladium for the synthesis of benzo-annulated oxacycles 144 (Scheme 8.37). To do so, they used an m-iodoaryl iodoalkyl ether 143, an alkene substimted with an electron-withdrawing group, such as t-butyl acrylate and an iodoalkane such as -BuI in the presence of norbomene. It is proposed that, after the oxidative addition of the aryliodide, a Mizoroki-Heck-type reaction with nor-bornene and a C—H activation first takes place to form a palladacycle PdCl, which is then alkylated with the iodoalkane (Scheme 8.37). A second C—H activation occurs and then, via the formation of the oxacycle OCl, norbomene is eliminated. Finally, the aryl-palladium species obtained reacts with the acrylate. The alkylation step of palladacycles of the type PdCl and PdCl was studied in more detail by Echavarren and coworkers [82] using computational methods. They concluded that, after a C—H activation, the formation of a C(sp )—C(sp ) bond between the palladacycle PdCl and an iodoalkane presumably proceeds by oxidative addition to form a palladium(IV) species to give PdC2. This stays, in contrast with the reaction between a C(sp )—X electrophile (vinyl or aromatic halide) and PdCl, to form a new C(sp )—C(sp ) bond which takes place through a transmetallation. 

In 1979, Tsuji s group [51] reported an alternative approach to macrolactonization. Inspired by their previous success in the preparation of recifeiolide and 9-decanolide, the authors envisioned that the dimethyl ether of zearalenone (6) could be obtained via olefination using the co-iodoalkyl phenylthioacetate 7 (Scheme 7.2). The Michael addition of diethyl malonate (11) to 10 followed by decarboxylation afforded an ethyl ester, which was reduced to alcohol and converted into the tosylate 12. Wacker-Tsuji oxidation of the terminal olefin was then followed by reduction of the ketone and conversion of the tosylate into iodide to provide 9. This was... 

The reductive cyclization of N-(w-iodoalkyl)succinimides induced by samarium(II) iodide was disclosed by Ha et al. as a novel method for making pyrrolizidines and indoUzidines (Scheme 46). " In the apphcation of the method to the synthesis of (+)-lentiginosine (127), reaction of N-(4-iodo-butyl)tartarimide (+)-335 with samarium(II) iodide in the presence of the iron(III)—tris(dibenzoylmethane) complex as catalyst produced the unsaturated indolizidin-3-one (+)-336 in 82% yield. Reduction of the bridgehead alkene was accomplished with triethylsilane and trifluoroacetic acid via an intermediate acyliminium ion, giving (+)-337 as the sole product in 93% yield. Routine hydrolysis of the silyl ethers produced the known diol (+)-177, after which reduction of the lactam with Hthium aluminum hydride then completed this short synthesis of (+)-127. 

Transformation of Cyclic Ethers into (0-Iodoalkyl Formates and of Aldehyde Cyclic Acetals into a,m-Alkanediol Esters by Hypothetical lodoxyl Radicaf°... 

The photolysis of cychc ethers with an excess of HgO-Ij reagent in benzene gives the corresponding iodoalkyl formates in one step tetrahydrofuran can be transformed into (O-iodoalkyl formate in 31% yield (Scheme 47). Aldehyde cyclic acetals lead to monoesters of ot,(D-alkanediols in one step (Scheme 48). The formation of the products can be rationalized by postulating iodoxyl radical participation, as outlined in the schemes. 

Suginome, H. and Wang, J.B., Photoinduced molecular transformations. 113. One-step transformations of cyclic ethers into co-iodoalkyl formates and of aldehyde cyclic acetals into monoesters of a,(0-alkanediols by iodoxyl radical, /. Chem. Soc., Perkin Trans. I, 2825, 1990. 

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