NaHMDS hexamethyldisilazide

Deprotonation of the benzo-l,3-dithiole dioxide 259 with -BuLi or sodium hexamethyldisilazide (NaHMDS) and subsequent reaction of the resulting carbanion with pivaldehyde gave a mixture of products 260 and 261 (Equation 21) <1995JO02174>. 

Sodium hexamethyldisilazide (NaHMDS) is a sterically demanding and strong but non-nucleophilic base. 

The Julia-Kocienski olefination of heterocyclic sulfones and aldehydes, which is an alternative to the modified Julia olefination, forms alkenes with good -selectivity. First, sulfone 54 is deprotonated in the a-position to the sulfur by sodium hexamethyldisilazide (NaHMDS) and the sulfur-stabilized anion 55 then adds to the alde-... 

Cbz Cp DABCO DBU DDQ (DHQD)2CLB (DHQD)2PYR DMF DME DMPU DMSO Et Fmoc HMPA ia KHMDS LDA LiHMDS Me MEM Ms NaHMDS Ph Piv PMB Pr Py (saltmen)Mn(N) benzyloxy carbonyl p 5 -cyclopentadienyl l,4-diazabicyclo[2.2.2]octane l,8-diazabicyclo[5.4.0]undec-7-ene 2,3 -dichloro-5,6-dicyanobenzoquinone dihydroquinidinyl p-chlorobenzoale (see Chart 1) dihydroquinidinyl pyrimidine (see Chart 1) dimethylformamide dimethoxyethane l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone dimethylsulfoxide ethyl 9-fluorenylmethoxy carbonyl hexamethylphosphoric triamide inverse addition potassium hexamethyldisilazide lithium diisopropylamide lithium hexamethyldisilazide methyl (2-methoxy ethoxy )methyl methanesulfonyl sodium hexamethyldisilazide phenyl pivaloyl p -methoxy benzyl propyl pyridine nitrido[A,A/-(l,l,2,2-tetramethyl) bis(salicylideneaminato)]manganese (see Chart 1)... 

Draw the structure of the products resulting from Wittig alkenylation of the ketone 11, and subsequent treatment with sodium hexamethyldisilazide (NaHMDS). Note that the base NaHMDS promotes the formation of the alkylidene carbene. 

Potassium hexamethyldisilazide, KHMDS, has been used successfully in the past for a-deprotonation of sulfoxides. Aiming to probe the nature of the transition state in the reaction of a-metalated (i )-methyl //-tolyl sulfoxide with A -(benzylidene) aniline under kinetic conditions, the effect of the choice of the bases for the a-deprotonation on the reactivity and diastereoselectivity was studied, using LDA, LHMDS, NaHMDS, and KHMDS. Best yields anddiastereoselectivities (90%, 84 16) were achieved with LDA, whereas LHMDS showed diminished reactivity (50%) without a loss of diastereoselectivity (87 13). Improved yields and lower diastereoselectivities were recorded in reactions mediated by NaHMDS and KHMDS, providing the amine in 60% (dr 81 19) and 77% (dr 69 31) yields and diastereoselectivities, respectively (eq 64). 

Phenyl-lff-tetrazol-5-yl sulfones were introduced as another alternative to phenyl sulfones, which led to alkenes in a one-pot procedure from aldehydes. Usually the highest selectivities are obtained while using KHMDS, although higher yields are observed with sodium hexamethyldisilazide. For instance, alkene 4 was obtained in 100% yield and an 84 16 E Z ratio with NaHMDS, whereas the use of KHMDS led to the same product with 59% yield and a 99 1 E Z ratio (eq 41). 

Scheme 11.49. A synthesis of periplanone A (after Hauptmann, H. Mtlhlbauer, G. Sass, H. Tetrahedron Lett., 1986, 6189). LDA = lithium diisopropyl amide p-TsCl = para-toluenesulfonyl chloride NaHMDS = sodium hexamethyldisilazide DMAP = 4-dimethyl-aminopyridine TMSCl = trimethylchlorosilane PCC = pyridiniumchlorochromate TBHP = f-butyl hydrogen peroxide TBDMSCI = f-butyldimethylchlorosilane TBAF = tetrabutylammonium fluoride Cp = cyclopentenyl.

This methodology is applicable to the synthesis of a-fluoro- and a-bromo-a,j8-unsat-urated esters [179-183]. Sodium hexamethyldisilazide (NaHMDS) or LDA/KOBu can also be used as a base, and give better yields in some cases. 

Anilides 80 have been synthesized through acylation of o-fluoroanilines by carbonylimidazole dimer (diimidazo[l,5-a l,5-tf]-pyrazine-5,10-dione, 84a) in the presence of sodium hexamethyldisilazide (NaHMDS) (Scheme 4.37) (Barrish and Spergel 2001 Norris et al. 2001). 

Enolates can also be used to assemble bicyclo[4.2.0] octanes (Scheme 19.25). Lee and co-workers treated trien-one 100 with sodium hexamethyldisilazide (NaHMDS) in refluxing 1,2-dimethoxyethane for 12 hours to produce tricyclic product 101 of unspecified stereochemistry in 47% yield. Several features contribute to the interest of this reaction. The 6ti-electrocyclization of the sodium enolate that is derived from 100 evidently does not compete with the 871-electrocyclization. The enolate may facilitate the 8ti-/671-cascade process in a similar way as with the anionic... 

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