Lithium derivatives from alkenes

Isoxazolines, derived from alkenes and nitrile oxides, undergo ring cleavage with lithium di-isopropylamide to form enoximes (Scheme Subsequent... 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Kuzuhara and his coworkers synthesized (+)-205 by hydroxylation of the alkene 304, which was prepared from the chiral azidocyclohexene derivative (303) derived from D-glucose, in which a novel rearrangement of the C - C double bond accompanying reduction of the azido group with lithium aluminum hydride was observed. 

In a parallel study, Wipf and Fritch11041 have shown that also urethane-protected (Boc), and even amino acid segments, are tolerated as acyl compounds on the aziridine nitrogen. The best results were obtained with alkylcopper reagents derived from CuCN and an alkyl-lithium in the presence of boron trifluoride-diethyl ether complex. Some 6-alkylated compounds (11-15%) were isolated as well. This work was extended to a solid-phase procedure that resulted in resin-bound alkene isosteres that could immediately be used in further peptide synthesis.11051 For this purpose, the 2-nitrophenylsulfonyl (oNbs) group was used for nitrogen protection and aziridine activation. It could be readily cleaved with benzenethio-late, which was compatible with the acid-sensitive Wang linker used. 

The well-known /(-elimination of fluoride from perfluoroalkylmetal compounds to fluoro-alkenes, which demands the handling of magnesium and lithium derivatives of this type at low temperatures (or formation as intermediates), is mentioned in Section 3.3.1. 

L-Rhodinose (174) was prepared from the readily available L-rhamnose.269 The method required deoxygenation of C-2 and C-3 and inversion of configuration at C-4 (Scheme 56). Oxidation of 187 with ruthenium dioxide-IOj, followed by reduction of the keto groups with lithium aluminum hydride yielded the alcohol 188. After protection as the benzyl derivative, an alkenic linkage was... 

In an unconventional cyclopentenone synthesis, Negishi cyclised vinyllithiums derived from the 1-iodo- 1-silyl alkenes 103 onto preformed lithium carboxylate salts.57 He later found58 that amides 104 function in this reaction rather better than the carboxylate salts, and that the silyl substituent is not necessary for cyclisation. Nitriles, on the other hand, fail to cyclise. 

The reaction of the dimethyl-derivative (27) with butoxide ion might be expected to produce the chlorocyclopropene (28) however, in practice two eliminations occur to produce (31) and the carbene (30), which can be trapped by an added alkene. Both products may be derived from (28), by a 1,4- or a formal 1,2-elimination respectively a study using a 14C-label at C-l of (27) showed that the carbene (30) was formed with the label exclusively at C-l, suggesting elimination via (29)32). However, in a related study, the isolated cyclopropene (28) labelled with 12C at C-l has been shown to react with methyl lithium to produce the carbene (30) labelled only at C-2 this suggests either that the reaction of (28) with butoxide follows a completely different course to that with methyl lithium, or that (28) is not involved in the reaction of (27) with base33). In a similar reaction the dichloride (32) has been shown to react with t-butoxide in DMSO to produce the allene (33) the product may be explained in terms of initial elimination to produce (34), followed either by rearrangement to the alkyne (35) and then elimination or by direct 1,4-elimination as in (36), followed in either case by a prototropic shift. Whatever the mechanism, a 12C-label at Ca in (32) is found at Ca in (33) 33). 

Reaction of (180, X = Cl) with methyl lithium in the presence of alkenes at ambient temperature leads to apparent carbene adducts (183), in this case derived from ring opening of (181) to the highly functionalised isoprenoid carbene (182). Surprisingly, the bromide (180, X = Br) reacts by a different course, leading to (184), apparently through initial lithium-bromine exchange followed by 1,3- rather than 1,2-elimination of LiCl 130>. 

Several perfluoroalkene derivatives have been made and used successfully in synthesis. Trifluorovinylmagnesium bromide and the lithium derivative may be obtained [39 1] from bromotrifluoroethene but preparation from HFC 134a, which involves metallation of trifluoroethene generated in situ, is now the more accessible route (see Section lA). However, direct metallation of fluorinated alkenes and fluorinated cycloalkenes has also been reported [26, 28] (Figure 10.9). 

Oxaziridines. Davis has developed the use of chiral 2-sulfonyloxaziridines derived from camphorsulfonic acid as chiral auxiliaries in the asymmetric oxidation reactions. Although other oxaziridines may be preferable, the camphor-derived oxaziridines can be used for the oxidation of sulfides and disulfides to sulfoxides and thiosulfinates as well as for the epoxidation of alkenes. On the other hand, the camphoryloxaziridines are the preferred reagents for hydroxylation of lithium enolates of esters, amides, and ketones, as utilized in the synthesis of kjellmanianone (eq 17). ... 

Few ester enolate crystal structures have been described. The lack of structural information is no doubt due to the fact that the ester enolates undergo a-elimination reactions at or below room temperature. A good discussion of the temperatures at which lithium ester enolates undergo this elimination is presented in the same paper with the crystal structures of the lithium enolates derived from r-butyl propionate (163), r-butyl isobutyrate (164) and methyl 3,3-dimethylbutanoate (165). It is significant Aat two of the lithium ester enolates derived from (163) and (165) are both obtained with alkene geometry such that the alkyl group is trans to the enolate oxygen. It is also noteworthy that the two TMEDA-solvated enolates from (163) and (164) are dimeric, while the THF-solvated enolate from (165) exists as a tetramer. 

Preformed iminium salts have been used extensively in organic synthesis. The facility of the condensation is a function of iminium salt substitution. Treatment of formaldehyde-derived methyl(methylene)ammonium halides (or trifluoroacetates) (46) with Grignard and lithium reagents results in the high yield formation of dimethylaminomethyl-containing compounds (47). Subsequent oxidation or alkylation of these products has been employed to generate terminal alkenes (48 Scheme 7). As expected, addition yields are modest for the mote-hindered iminium salts derived frrom other aldehydes and are somewhat lower for those derived from cyclic ketones. ... 

The anions of nitroalkanes (nitronates) can be used as precursors in a connective and regiospecific synthesis of tetrasubstituted alkenes. They are easily formed on reaction with LiOMe and undergo oxidative dimerization in the presence of bromine. The resultant 1,2-dinitroalkanes (Scheme 37) participate in a reductive elimination involving an rc1 radical chain mechanism when irradiated in the presence of Na2S, PhSNa or the lithium nitronate derived from 2-nitropropane. 

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