Vinyl iodide condensation

Many examples of the use of chiral Ca-symmetric bis(oxazoline) hgands have been presented here. Other examples include their use in various heteroannulations, one of which is shown in Figure 9.69. Here, the vinyl iodide, (Z)-3-iodo-2-methyl-2-propen-l-ol, 235 is condensed with 1,2-undecadiene to form the 3-methylene-2//-pyran derivative 237. " When this reaction was mn in the presence of 10 mol% of bis(oxazoline) Ugand 236 complexed with palladium(ll), 237 was produced in 70% yield with 79% ee. 

The synthesis of the 10-methoxytetracyclic ketone 353 (Scheme 26) started from the readily available 3-methyl-5-methoxyindole 355, which after Boc protection, was brominated, and then condensed with the anion of the Schollkopf auxiliary 356 (from l-valine). Removal of the Boc-protecting group, followed in succession by A -methylation and hydrolysis, gave the required A -methyl-5-methoxy-D-tryptophan ethyl ester 357, which was then transformed into the key 10-methoxytetracyclic ketone 353, via N-benzylation, Pictet-Spengler condensation, and Dieckmann cyclization. Subsequent N-alkylation by the vinyl iodide 358 followed by Pd-catalyzed (enolate-driven)... 

B. Trimethylvinyltin. To a dry, 1-L, three-necked, round-bottomed flask, equipped with a Dewar-type condenser cooled to -78°C, a magnetic stirring bar, and a gas inlet leading to a static supply of dry argon (Note 1), are added 11.4 g (0.469 mol) of clean magnesium turnings, 50 raL of dry tetrahydrofuran (Note 10), 3 mL of vinyl bromide, and 0.3 irt. of methyl iodide to initiate... 

The benzene derivatives containing the fluorinated sulfone have been prepared either by nucleophilic substitution of the 4-fluorophenyl derivative (e.g. 1) or by starting with the appropriately substituted sodium thiophenoxide and reacting with perfluoroalkyl iodide follow by oxidation with either MCPBA or chromium oxide (12. li.) The biphenyl derivatives have been prepared by palladium catalyzed cross coupling chemistry of the 4-bromophenyl derivative (e.g. 2) with substituted phenyl boronic acid (yields 37-84%) (JLH, .). Compound 16 has been prepared by palladium catalyzed cross coupling of (4-bromophenyl)perfluorohexyl sulfone with vinyl anisole in 37 % yield (JJL). The vinyl sulfones, 7 and 9, have been prepared by condensation of CH3S02Rf (JJL) with the appropriate aldehyde (yields 70,and 73%) following a literature procedure (1 ). Yields were not optimized. 

Certain substituted sulfones may be obtained by special methods for instance, vinyl sulfones (82) may be formed by addition of a sulfonyl carbanion (83) to a carbonyl compound followed by elimination (Scheme 34). An example when X = H is the synthesis of methyl styryl sulfones (84) by the Knoevenagel condensation of an aromatic aldehyde with a methanesulfonylacetate (85) followed by dealkylation-decarboxylation of the intermediate product by treatment with lithium iodide in DMF (Scheme 35). 

In l-hthio vinyl sulfides (sec. 8.6) the sulfur atom stabilized the carbanion, allowing either alkylation or condensation reactions. The sulfonyl moiety can also stabilize a vinyllithium derivative. Vinyl sulfone (321), for example, was converted to the 1-lithio derivative with methyllithium.332 xhis organometallic reacted in the usual manner with alkyl halides (methyl iodide) to give the coupling product, 322. 

The required 2-(4-methoxybenzocyclobutenyl)-ethyl iodide 79 was prepared by a multistep process from 2-bromo-5-methoxybenzaldehyde via l-cyano-4-methoxybenzocyclobutene 77 as illustrated. 2-Methylcyclohexenone was then converted into 2-methyl-3-vinyl-6-n-butylthiomethylenecyclohexanone 80. Blocking C-6 was considered necessary to insure regiospecihc condensation of 79 at C-2. However, the condensation reaction afforded adduct 81 in only 16% yield. In subsequent work (with 2-methylcyclopentenone) 1 4 addition of a vinyl Grignard or lithium reagent and coupled alkylation of the intermediate enolate occurred at C-2 without the need to block C-6 (Scheme 1, Scheme 14 - ). 

Condensations of amines with 1-chlorocycloheptene in the presence of the complex base , sodamide and sodium t-butoxide, gave mixtures of enamines and cyclo-hepta-1,2-diene dimer. Excess n-butyl-lithium has been used to convert vinyl and aryl bromides into organolithium compounds which undergo useful reactions with, for example, benzophenone, dimethyl disulphide, diphenyl disulphide, trimethylsilyl chloride, and methyl iodide. Hence 1-bromo-cis-cyclononene was converted into 1-methylthio-cis-cyclononene via 1-lithio-cis-cyclononene the 1-methylthio... 

A key driver for the development of the DBR has been the increased availability of the requisite chromium carbene. Fischer carbenes undergo a wide variety of useful reactions and a significant effort has been devoted to their synthesis. These carbenes undergo many of the same reactions as esters. The a-hydrogens in 13 are quite acidic, with a pKa of approximately 8, that allows for application of the Aldol condensation to form the vinyl-substituted carbene 14. Of course, alkynes insert into these carbenes to form new vinyl substituted carbenes 15. However, the absence of a heteroatom on the carbene center makes these poor substrates for the DBR. The classical route to Fischer carbenes is the Fischer route addition of an organolithium to hexacarbonyl chromium and alkylation with a hard electrophile. Hoye has also shown that alkyl iodides under phase-transfer conditions can be used to alkylate the lithium alkoxide. Thus reaction of vinyl lithium 16 provides the carbene 17 in 53% over two steps. 

Michael-Peterson Condensation. 3-Trimethylsilyl-3-buten-2-one also undergoes smooth Michael addition with Grignard reagents (R = Me, n-Pr, i-Pr, f-Bu, Ph), generating magnesium enolates which are then trapped with benzaldehyde to give ( )-and (Z)-enone isomers after Peterson condensation (eq 6). For example, treatment of the a-silyl vinyl ketone with methylmagne-sium iodide followed by reaction with benzaldehyde yields a 7 1... 

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