Benzyl-diisopropyl

Palladium-catalysed deprotonative cross-coupling a-arylation of benzyl diisopropyl phosphonate derivatives (582) have been presented by Walsh and co-workers as a new, efficient synthetic route to access diatylmethyl phosphonates (583) (Scheme 169). ° ... 

To a stirred solution of 130.4 parts of potassium cyanide and 243.2 parts of piperidine hydrochloride in a mixture of 800 parts of water and 320 parts of ethanol is added portionwise 378 parts of 1 -benzyl-4-piperidone. After about one hour a solid starts to precipitate. Stirring is continued for 24 hours. The reaction mixture is filtered and the solid is recrystallized from 1,200 parts of diisopropyl ether. On cooling to room temperature a first crop of 1-benzyi-4-cyano-4-piperidinopiperidine melting at about 104°C to 106°C is obtained. 8y concentrating and further cooling of the mother liquor a second crop of the above compound is obtained. 

Protecting diisopropyl ether against oxidation requires 16 ppm of N-benzyl-4-aminophenol or 50 ppm of diethylenetriamine. 

Example 19 Crich and Dudkin have used phosphoroamidite containing two different protecting groups 0-benzyl-0-2-cyanoethyl-iV,Ar-diisopropyl-phosphoroamidite [48]. This phosphitylating reagent was prepared in excellent yield from 2-cyanoethyl NyN diisopropylchlorophosphoroamidite, which was immediately used for coupling with an appropriate alcohol in the presence of tetrazole and oxidized without delay with TBHP. This kind of phosphorylation procedure was used in the synthesis of 4,8,12,16,20-pen-tamethyl-pentacosylphosphoryl / -o-mannopyranoside, an unusual / -man-nosyl phosphoisoprenoid from Mycobacterium avium. 

First phosphitylation was performed by 0-benzyl-bis(iV,iV,-diisopropyl)-phosphoroamidite in the presence of diisopropyl-ammonium tetrazolide at room temperature in dichloromethane solution (step a). The intermediate phosphoroamidite was coupled with a glycerol moiety in the presence of tetrazole in boiling CH2CI2 to give the benzyl phosphite (step b), which was oxidized by CPBA in CH2CI2 into the corresponding phosphate (step c). In the final step d total debenzylation was achieved by Pd/C transfer hydrogenol-ysis in the presence of formic acid and methanol at room temperature. 

The best compromise with respect to reactivity and availability of the starting material was the use of diisopropyl malate 107. This malic acid ester is easy to prepare and its alkylation with various benzyl bromides can be achieved with good yields (53-67%, not optimized) and high stereoselectivities (dr 95 5 for 120 and 121). An exception with respect to the stereoselectivity was the 2,4,6-trimethylbenzyl substituted succinate 122, which was obtained in a dr of only 83 17 (Fig. 6) [71]. 

The chiral, nonracemic, 6-monosubstituted bicyclic lactams 1 are deprotonated by a strong base (usually lithium diisopropyl amide) and then alkylated with an iodoalkane or an allylic or benzylic bromide. Alkylation preferentially takes place from the side opposite to that of the substituent R1, which is usually an alkyl or an aryl group. While the diastereomeric ratios may be as low as 75 25, they are most often >90 10 (see Table 9). The minor diastereomer can in most cases be easily removed by liquid chromatography and/or recrystallization to yield the pure major diastereomer. 

One of the more common pathways for the metabolic transformation of tertiary amines involves A -dealkylation to a secondary amine. The observation that those products often show the same biological activity as the parent dmg in many cases confounds the issue of the identity of the chemical species responsible for the drug s action. The fact that the dealkylation product of disobutamide shows antiarrhythmic activity in its own right prompted the synthesis of the acetyl derivative of that secondary amine this agent may be considered a latent form of the active metabohte. This compound is prepared by first repeating the penultimate step in the disobutamide synthesis using (Af-benzyl-Af-isopropyl)-2-chloroethylamine instead of the diisopropyl intermediate. The product from that reaction (56-1) is then hydrolyzed to the... 

Edifenphos, O-ethyl 5,5-diphenyl phosphorodithioate, was announced in 1968 and introduced commercially by Bayer AG for the control of rice blast, Pyricularia oryzae. Iprobenfos, 5-benzyl 0,0-diisopropyl phosphorothioate, was introduced by Kumiai Chemical... 

To a stirred solution of 2,3,4,6-tetra-O-benzyl-D-glucopyranose (3 540 mg, 1 mmol) in CHC13 (5 mL) under argon was added 1-fluoro-A, Ai-diisopropyl-2-methylprop-1 -enamine (2 173 mg, 1.1 mol) at rt. The reaction was followed by TLC. Once the reaction was complete, the solvent was removed under reduced pressure and the residue subjected to flash chromatography (silica gel, petroleum ether/EtOAc 2 1) to give 4 yield 537 mg (99%) (a// ) 28 72. 

Other chemicals which inhibit milk lipase include hydrogen peroxide, animal cephalin, sodium arsenite, diisopropyl fluorophosphate, 2,4 din-itro-l-fluorobenzene, p-hydroxymercuribenzoate, potassium dichromate, lauryl dimethyl benzyl ammonium chloride, aureomycin, penicillin, streptomycin, and terramycin (Schwartz 1974). 

N,N -Dibenzyl- or -diisopropyl-formamidines react84 with Os3(CO)l2 or Os3(CO)i0(cyclooctene)2 to give different types of nonacarbonyl, HOs3(CO)9(PriNCHNPr1) and HjOs CO),-(PhCH2NCHNCH2C6H4), the difference being in the ability of the benzyl group to be ortho-metal-... 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

AD-mix-P 9-BBN Bn Boc Bz BOM CDI m-CPBA CSA Cy DBU DDQ DEAD DIAD DIBAL-H DIPT DME DMF DMAP DMSO EDC HMPA HOBT KHMDS LDA MEM MOM MoOPH NaHMDS NBS NMM NMO Piv PMB Reagent for Sharpless asymmetric dihydroxylation 9-Borabicyclo[3.3.1 ]nonyl Benzyl t-Butoxy carbonyl Benzoyl B enzyloxy methyl Carbonyldiimidazole m-Chloroperoxybenzoic acid Camphorsulfonic acid Cyclohexyl 1,8 -Diazabicy clo[5.4.0] undec-7-ene 2,3 -Dichloro-5,6-dicyano-p-benzoquinone Diethyl azodicarboxylate Diisopropyl azodicarboxylate Diisobutylaluminum hydride Diisopropyl tartrate Dimethoxyethane A,N-Dimethylformamide 4-Dimethylaminopyridine Dimethyl sulfoxide N-(3-Dimethylaminopropyl)-A -ethylcarbodiimide Hexamethylphosphoramide 1 -Hydroxybenzotriazole Potassium hexamethyldisilazane Lithium diisopropylamide Methoxyethoxymethyl Methoxymethyl Oxidodiperoxymolybdenum(pyridine)(hexamethylphophoramide) Sodium hexamethyldisilazane N - Bromosuccinimide A-Methylmorpholine A-Methylmorpholine A-oxide Pivaloyl /j-Methoxybenzyl... 

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