Ethers, vinyl with alkyl halides

Like magnesium, lithium reacts with alkyl halides, vinyl halides, and aryl halides to form organometallic compounds. Ether is not necessary for this reaction. Organolithium reagents are made and used in a wide variety of solvents, including alkanes. 

Vinyl selenides have been lithiated at the a-position by LDA983,984 at —78 °C in THF to give a-(arylselanyl)vinyllithiums 680, a-(methylselanyl)vinyllithiums 681 being obtained by selenium-lithium transmetallation from l,l-bis(methylselanyl)alkenes with n-BuLi in THF or t-BuLi in ether at —78 °C985 986. These intermediates reacted with alkyl halides, epoxides, carbonyl compounds and DMF985, the final deprotection being performed by mercury(II) salts986. 

The first palladium-catalyzed formation of aryl alkyl ethers in an intermolecular fashion occurred between activated aryl halides and alkoxides (Equation (28)), and the first formation of vinyl ethers occurred between activated vinyl halides and tin alkoxides (Equation (29)). Reactions of activated chloro- and bromoarenes with NaO-Z-Bu to form /-butyl aryl ethers occurred in the presence of palladium and DPPF as catalyst,107 while reactions of activated aryl halides with alcohols that could undergo /3-hydrogen elimination occurred in the presence of palladium and BINAP as catalyst.110 Reactions of NaO-/-Bu with unactivated aryl halides gave only modest yields of ether when catalyzed by aromatic bisphosphines.110 Similar chemistry occurred in the presence of nickel catalysts. In fact, nickel catalysts produced higher yields of silyl aryl ethers than palladium catalysts.108 The formation of diaryl ethers from activated aryl halides in the presence of palladium catalysts bearing DPPF or a CF3-subsituted DPPF was also reported 109... 

The addition of a cation to an olefin to produce a carbonium ion or ion pair need not end there but may go through many cycles of olefin addition before the chain is eventually terminated by neutralization of the end carbonium ion. Simple addition to the double bond is essentially the same reaction stopped at the end of the first cycle. The addition of mineral acids to produce alkyl halides or sulfates, for example, may be prolonged into a polymerization reaction. However, simple addition or dimerization is the usual result with olefins and hydrogen acids. The polymerization which occurs with a-methyl-styrene and sulfuric acid or styrene and hydrochloric acid at low temperatures in polar solvents is exceptional.291 Polymerization may also be initiated by a carbonium ion formed by the dissociation of an alkyl halide as in the reaction of octyl vinyl ether with trityl chloride in ionizing solvents.292... 

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

Partially fluorinated vinyl ethers of fluoroolefins are quite susceptible to the action of Lewis acids. Reaction usually proceeds with ionization of the allylic C-F bond and results in formation of C=0 group and elimination of alkyl halide. Indeed, 3-chloro-2-methoxyhexafluoro-2-butene 82 reacts with A1C13 with formation of trichlorovinyl ketone 83, and cyclic alkoxyfluoroalkenes demonstrate similar behavior in reaction with aluminum or tin(IV) halides [170] ... 

The method is an extension of the well-known Grignard synthesis in ethers to the use of nonsolvating media, and is a development of procedures previously reported.2-6 A version of it has been employed with straight-chain primary alkyl chlorides, bromides, and iodides from C2 to Cu,5-7 and in solvents (or an excess of the halide) which permit reaction temperatures above 120°, with simple aryl halides such as chlorobenzene and 1-chloro-naphthalene. Branched-chain primary, secondary, and tertiary alkyl halides, allyl, vinyl, and benzyl halides either fail to react or give extensive side reactions. Better results are reported to be obtained in such cases with the use of catalytic quantities of a mixture of an alkoxide and an ether such as diethyl ether or tetrahydrofuran in a hydrocarbon medium, but the products are not, of course, completely unsolvated.4... 

Cellulose Ethers. Cellulose ethers are formed when cellulose, in the presence of alkali or as alkali cellulose, is treated with alkyl or arylalkyl halides. Two types of reaction are employed in the preparation of cellulose ethers. The most common is nucleophilic substitution. Methylation of alkali cellulose with a methyl halide is an example of this type. The other type of etherification reaction is Michael addition. This reaction proceeds by way of an alkali-catalyzed addition of an activated vinyl group to the cellulose. The reaction of acrylonitrile with alkali cellulose is a typical example. The general reaction is outlined in Scheme 4. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

However, Lewis acid not only ionizes the alkyl halide, but may also complex with a nucleophilic oxygen atom. This reaction is important in the presence of both excess vinyl ether (monomer) and excess polymer. We will return to this reaction in Section IV.C.2. 

Carbenium ions can be generated not only by ionization of alkyl halides with Lewis acids, but also by protonation of double bonds. Unfortunately, addition of excess triflic acid to a vinyl ether leads to polymer rather than to the monomeric cation [Eq. (6)]. 

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