Tetrahydro-3,5-dimethyl

Attempts were made to substitute other polar solvents for HMPA in this reduction. Under similar reaction conditions but with substitution of.1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) no reaction took place, and the starting... 

Fluoride ion catalyzes the hydrosilylation of both alkyl and aryl aldehydes to silyl ethers that can be easily hydrolyzed to the free alcohols by treatment with 1 M hydrogen chloride in methanol.320 The most effective sources of fluoride are TBAF and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). Somewhat less effective are CsF and KF. Solvent effects are marked. The reactions are facilitated in polar, aprotic solvents such as hexamethylphosphortriamide (HMPA) or 1,3-dimethyl-3,4,5,6-tetrahydro-2(l //)-pyrirnidinone (DMPU), go moderately well in dimethylformamide, but do not proceed well in either tetrahydrofuran or dichloromethane. The solvent effects are dramatically illustrated in the reaction of undecanal and dimethylphenylsilane to produce undecyloxyphenyldimethylsi-lane. After one hour at room temperature with TBAF as the source of fluoride and a 10 mol% excess of silane, yields of 91% in HMPA, 89% in DMPU, 56% in dimethylformamide, 9% in tetrahydrofuran, and only 1% in dichloromethane are obtained (Eq. 164).320... 

As an extension of their work on the [4+ 4]-reaction of zirconacyclopentadienes and l,2-bis(bromomethyl)arenes (Section 10.13.2.4), Takahashi and co-workers reported a [5 + 4]-reaction based on the use of l,8-bis(bromomethyl)-naphthalene as the five-carbon component.85 As with the [4 + 4]-reaction, the [5 +4]-reaction works with a catalytic amount of CuCl, but higher yields and faster reactions result when stoichiometric CuCl and 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone(iV,iV -dimethylpropyleneurea) (DMPLJ) are used (Scheme 42). 

Oxindoles are prepared using a solid-phase Pummerer reaction. Thus, the immobilized amide 182 undergoes the Pummerer rearrangement on treatment with TFAA and boron trifluoride diethyl etherate (BF3 Et20) (Equation 118). Cleavage of the oxindole from the linker is achieved using samarium iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU) <2003CC2380>. 

After selective generation of the syn- or anH -enolate of an amide, it is usually reacted with a haloalkane, often the iodide. Allylic and benzylic bromides also react satisfactorily, and dimethyl and diethyl sulfate have also been used in some cases. A solution of the alkylating agent in an ethereal solvent, usually tetrahydrofuran, is added to the enolate, usually at low temperature. A polar, aprotic cosolvent, such as hexamethylphosphoric triamide, is frequently used as an additive in the alkylation step. The use of this suspected carcinogen is prohibited in some countries, which limits the usefulness of many of the reactions described below. However, similarly effective in many cases are some ureas, such as the commercially available 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU)12. 

BASF AG CRBPII dba DBN DBU DIBAL-H DMAP DMF DMF-DMA DMPU HMDS HMPA HMPT H-LR LDA LDE LRAT MCPBA MOM NMO NMP PCC PhH = Badische Anilin- Soda Fabrik AG = cellular retinol-binding protein type II r dibenzylideneacetone = 1,5-diazabicyclo[4.3.0]non-5-ene = l,8-diazabicyclo[5.4.0]undec-7-ene = diisobutylaluminium hydride = 4-dimethylaminopyridine = A V-dimethylformamide = A,V-dimethylformamide, dimethylacetal = 1,3 -dimethyl-3,4,5,6-tetrahydro-2( 1H)-pyrimidone = hexamethyldisilazane = hexamethylphosphoramide = hexamethylphosphorous triamide = Hoffmann-La Roche = lithium diisopropylamide = lithium diethylamide = lecithin retinol acyltransferase = m-chloroperbenzoic acid = methoxymethyl = iV-methylmorpholine oxide = l-methyl-2-pyrrolidinone = pyridinium chlorochromate = benzene... 

Hexamethylphosphoric triamide is distilled from calcium hydride under reduced pressure of nitrogen. In place of hexamethylphosphoric triamide, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone (DMPU). which is dried and purified similarly,7 can be used. 

Let us turn now to the other coupling partner, aldehyde 58 it was synthesised by the pathway shown in Scheme 17.18. The first step was a Sharpless catalytic asymmetric epoxidation on ( )-crotyl alcohol with the oxidant derived from (—)-diethyl tartrate. An in situ derivatisation with r-butyldiphenylsilylchloride was then performed. The desired epoxide 59 was readily isolated in 76% overall yield after chromatography. Treatment of 59 with 2-lithio-l,3-dithiane in THF and 1,3-dimethyl-3,4,5,6-tetrahydro-2(l/7)-pyrimidinone (DMPU also known as N,N-... 

DBPO DBU DCC DDQ DEAD DET DIBAL-H DIPT DMAP DMB DME DMF DMPU DMSO EDDA Eu(dppm)3 Eu(fod)3 dibenzoyl peroxide 1.8- diazabicyclo [ 5.4.0] undec-7-ene dicyclohexylcarbodiimide 2.3- dichloro-5,6-dicyano-l,4-benzoquinone diethyl azodicarboxylate diethyl tartrate diisobutylaluminium hydride diisopropyl tartrate iMM-dimethylaminopyridine 3.4- dimethoxybenzyl 1.2- dimethoxyethane dimethylformamide 1.3- dimethyl-3,4,5,6-tetrahydro-2(lH)pyrimidinone dimethyl sulfoxide ethylene diammonium diacetate di(perfluoro-2-propoxypropionyl)methanato europium 6.6.7.7.8.8.8- heptafluoro-2,2-dimethyl-3,5-octanedionato... 

Because of the product s volatility, a hot water bath should not be used during solvent evaporation. GC and GC/MS analysis of an aliquot indicate that the product ranges in purity from 75-95% with unreacted 1-iodoheptane also present. The addition of 0.5 equiv of hexamethylphosphoramide (HMPA) prior to addition of the iodoheptane was found to improve the yield of this alkylation. The addition of 0.5 to 2.0 equiv of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (DMPU) did not improve the yield. The checkers found the following GC conditions useful for monitoring the alkylation reaction initial column temperature, 40°C heating increment, fO°C/min iodoheptane R = 3.3 min, product R = 5.7 min. Column specifications were as follows SPB-f (stationary phase), fused silica gel capillary column, 30 m x 0.32 mm ID, 0.25-p.m film thickness. 

More recently, a new molybdenum complex, oxodiperoxymolybdenum-pyridine 3,4,5,6-tetrahydro-1,3-dimcthyl-2-(l //)-pyrimidinonc (MoOs py DMPU = MoOPD) has been introduced in which 1,3-dimethyl-3,4,5,6-tetrahydro-2(lf/>pyrimidinone (DMPU) is used as a non-carcinogenic alternative to HMPA54. This reagent offers comparable results to MoOPH reagent in the oxygenation of enolates (Table 4). 

Similar conditions have been applied to 2-methy -3-oxoamides, except that tris(diethyl-amino)sulfonium difluorotrimethylsilicate (TASF) was used as the fluoride source and 1,3-dimethyl-3,4,5.6-tetrahydro-2(l//)-pyrimidinone (DMPU) as solvent3,4. Again the results were generally complementary to those given by the silane/trifluoroacetic acid system, in that the ewfi-product w as formed predominantly. However, the method only worked reliably for amides where R1 is aryl. The ester (5)-methyl 2-benzoylpropanoate failed to react, possibly because of deprotonation by fluoride4. 

DMPU 1,3-Dimethyl-3,4,5,6-tetrahydrO 2( IH)- SnI Unimolecular nucleophilic substitution... 

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