Alkenes reductive lithiation

Synthesis of Dienes via Peterson Alkenation. Reductive lithiation of 2-(phenylthio)-2-(trimethylsilyl)propane with lithium l-(dimethylamino)naphthalenide (LDMAN) furnishes 2-lithio-2-(trimethylsilyl)propane, which is an intermediate for Peterson alkenation. The specific example in eq 1 features silicon-directed diene synthesis. ... 

Our strategy for the Smij-promoted synthesis of l,2-cis-C-glycosides is illustrated in Figure 3. It was assumed that one-electron transfer to the LUMO of the aryl sulfone group in A would result in concomitant cleavage of the C1 -S bond liberating an anomeric radical intermediate, as previously observed in the reductive lithiation of glycosyl phenyl sulfones." If 5-exo cyclization onto the silicon-tethered alkene/alkyne is substantially favored over a second electron transfer from Smij, then the exocyclic carbon radical B would ultimately be formed. On the other hand, reduction of the Cl-radical by... 

An example is the preparation of allylidenecyclopropanes (Scheme 4S). The l-(trimethylsilyl)cyclo-propane (312) is reductively lithiated with lithium l-(dimethylamino)ntq)hthalenide (LDMAN) followed by addition of an aldehyde to form the 3-silylcarbinol (314). This method of anion formation is general but has seen greatest application in the synthesis of cyclopropyl compounds. The intermediate can be eliminated in situ with KOBu to form the alkene (315). Yields are good but, as discussed in the mechanistic section, in unsymmetrical cases a mixture of products results. This reaction has been extended by Halton and Stang to the synthesis of cycloproparenes. ... 

Peterson Alkenation. l-Lithio-l-(trimethylsilyl)cyclopro-pane, derived from l-phenylthio-l-(trimethylsilyl)cyclopropane by reductive lithiation with lithium l-(dimethylamino)naphtha-lenide (LDMAN), condenses with aldehydes to give carhinols which are converted to alkylidenecyclopropanes under Peterson alkenation conditions (eq 1). ... 

An interesting Fe-catalyzed SN2 -like carbene insertion reaction using diazo compounds and allyl sulfides (the Doyle-Kirmse reaction) was reported by Carter and Van Vranken in 2000 [20], Various allyl thioethers were reacted with TMS-diazomethane in the presence of catalytic amounts of Fe(dppe)Cl2 to furnish the desired insertion products with moderate levels of stereocontrol [Equation (7.6), Scheme 7.14]. The products obtained serve as versatile synthons in organic chemistry, e.g. reductive desulfurization furnishes lithiated compounds that can be used in Peterson-type oleftnations to yield alkenes [Equation (7.7), Scheme 7.14] [21]. 

With sulfides as intermediates, alkenes can be used as precursors to organolithiums with regioselectivity in the formation of 56 determined by whether a radical11 or polar73 thiol addition is employed. Easy lithiation of phenyl benzyl sulfide 57 makes substituted benzyllithiums such as 58 readily available.73 Reductive C-S cleavage is probably the best way of making benzylic organolithiums. 

An orf/io-directed lithiation allows the conversion of 25 to aryl iodide 40. Reductive ether formation of aldehyde 40 with crotyl alcohol yields compound 41. Intramolecular Heck reaction of 41 affords a mixture of the olefins 42 and 43. The undesired alkene 42 can be isomer-ized quantitatively to the desired enol ether 43 with Wilkinson s catalyst. Sharpless dihydroxylation ee 94 %) of the enol ether 43 provides lactol 44, which is oxidized directly to lactone 45. Finally, the pyridone-O-methyl ester is cleaved under acid conditions (45 — 7). 

Cycloheptatriene reacts with elemental sulfur in sulfolane at 70 °C and in the presence of pyridine in such a way that an S3 unit is added across the 1,6-positions, resulting in 2,3,4-trithiabicyclo[4.3.1] deca-6,8-diene (21% yield). Trimethylvinylsilane, Me3SiCH=CH2, and sulfur react at 55 °C in the presence of Fe3(CO)i2 to give, inter alia, l-trimethylsilyl-2,3,4,5,6-pentathiacycloheptane. The preparation of cycUc trisulfanes from alkenes and Sg has also been carried out by reduction with NaH in toluene in the presence of a phase transfer catalyst. Indole fused pentathiepines were obtained by lithiation of indole or N-methylindole followed by thionation with elemental sulfur. ... 

Lithiation of vinylic sulfones. Phenyl vinyl sulfones (1), prepared as indicated, react with methyllithium regiospecifically at — 95° at the a-vinyl position to give the lithium derivatives 2. As expected, 2 can be alkylated to give 3. The reaction of 2 with enolizable carbonyl compounds proceeds more satisfactorily by prior conversion to the vinylic Grignard reagent a. This sequence constitutes a route to disubstituted alkenes, since a sulfone group is reductively cleaved by sodium amalgam (7, 326). ... 

A serious obstacle to the use of the Julia alkenation for the synthesis of trisubstituted alkenes is illustrated in Scheme 31. Addition of cyclohexanone to the lithiated sulfone (86) gave intermediate (87), which could not be acylated under the reaction conditions because of the sterically hindered tertiary alk-oxide. Owing to an unfavorable equilibrium, (87) reverted back to starting materials. However, by reversing the functionality of the fragments a stable adduct (88) was formed in which the less hindered secondary alkoxide was acylated and the resultant -benzoyloxy sulfone (89) reductively eliminated to the alkene (90) in 54% overall yield. Trisubstimted alkenes have been generated by reductive elimination of 3-hydroxy sulfones ° but, in general, retroaldol reactions compete. 

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

Hunig bases, polymeric = animated cbloro-methylated ethenylbenzene homopolymers deprotonation with of ketones, 11 or phosphonium salts, 32 removal of acids with, 32 Hybrid plasmids, 243-245 Hydration. See Alkenes or Alkynes Hydrazine hydrazinolysis with of esters, 239-240,331 of phthaloyl-protected amines, 162,163 reduction of ketones with, 97-98,109 Hydrazines, cyclic oxn., N3 extrusion, 35,331 Hydrazones WolfF-Kishner redn. of, 109 —, aryl- indole synth. with, 151-152, 296, 307 —, dialkyl-, lithiated alkylation, 12, 18, 25-26 enantioselective (SAMP-hydrozones), 25-26 ozonolysis of, 26... 

The second recent variant, developed by Julia and co-workers, avoids reductive elimination altogether and provides a remarkable one-pot connective synthesis of alkenes. The procedure, illustrated in eq 14, involves condensation of an aldehyde or ketone with a lithiated benzothiazolyl alkyl sulfone to give an adduct which first cyclizes and then fragments with extrusion of sulfur dioxide, benzothiazolone (which then tautomerizes to 2-hydroxybenzothiazole), and the alkene. Generally a mixture of ( )- and (2)-alkenes is obtained, hut in stericaUy hindered substrates the ( ) isomer can be obtained selectively. The same reaction has been observed with the pyridinyl sulfone analogs, in which case the separable /8-hydroxy sulfone intermediates undergo stereospecific and elimination to the corresponding alkene. 

During the course of some work aimed at the selective reduction of a substituted alkyne to the c/5-alkene, Olsen et al have discovered the novel synthesis of a rare ring system. Lithiated alkynes were found to react with the halo-substituted phthalimide (360) at the carbonyl group rather than at the halogen-bearing carbon as expected. The intermediate cyclized to this position to give an oxazolo[2,3-a] isoindole (361). 

A route to 3,4-dihydroxy-l-alkenes (56) (Scheme 23) is based on the lithiation of allylsilyl ethers. Separation of cw-l,2-diols from mixtures, and the protection of such functionality. have been achieved by selective coupling to a polymeric boric acid derivative (57). An improved procedure for the Ti reduction of 1,2-diols to alkenes, using Rieke active Ti powder, has been published, and avoids the unpredictability of an earlier method. 

Peterson went on to describe reactions of several lithiated silanes with carbonyls compounds, all giving the desired alkenes in good yields, albeit with very little stereoselectivity. In 1975 however, Peterson and Hudrlik published their studies on the stereoselective elimination of the hydroxyalkylsilyls. The reduction of 5-trimethylsilyl-4-octanone 10 was carried out with DIBAL-H to give one diastereoisomer, 11. The authors found that elimination with sodium or potassium hydride gave /ra 5-4-octene as the major isomer 12, while elimination under acidic conditions resulted in predominantly c/5-4-octene 13. Mild conditions were employed, affording stereochemical purity of up to 95% with excellent yields. 

Scheme 88 demonstrates the compatibility of selenium linker systems with reductive, eliminative and nucleophilic conditions. The linker has been synthesized from polystyrene 604 via lithiation and quenching with dimethyld-iselenide 605 as mentioned above. Reaction to terminal alkenes 610 is performed via an oxidation-elimination process, induced by the addition of H2O2. Alkyl compound 609 is released using radical chemistry with a combination of AIBN and n-BusSnH [323]. 

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