N, A-Diisopropylethylamine

Solvents and scavengers dichloromethane (DCM), trifluoroacetic acid (TFA), N, A-diisopropylethylamine (DIEA), 100% ethanol, A,A-dimethylformamide (DMF), dimethylsulphoxide (DMSO), acetonitrile, trifluoromethanesulfonic acid (TFMSA), dimethylsulfide (DMS), p-cresol, dimercaptoethane. 

Scheme 4. Idealized sketches of gold surfaces for DNA hybridization sensors prepared by (a) chemisorption of thiolated ssDNA capture probes followed by chemisorption of a dilutor alkylthiol [168] and by (b) chemisorption of a mixed alkylthiol SAM followed by covalent attachment of an amino-terminated ssDNA capture probe (surface-bound carboxylic groups are activated by reaction with 0-(N-auccimrmdyl)-N,N,N, N -tetramethyluronium tetrafluoroborate in acetonitrile in the presence of N, A-diisopropylethylamine, [172]).

Several optimization studies have been carried out under these phosphine-free conditions. The reaction of bromobenzene and styrene was studied using Pd(OAc)2 as the catalyst, and potassium phosphate and (V,(V-dimethylacetamide (DMA) were found to be the best base and solvent. Under these conditions, the Pd content can be reduced to as low as 0.025 mol %.142 The reaction of substituted bromobenzenes with methyl a-acetamidoacrylate has also been studied carefully, since the products are potential precursors of modified amino acids. Good results were obtained using either N, (V-diisopropylethylamine or NaOAc as the base. 

Scheme 5.24. Stereoselective synthesis of aspicilin C3-C9 fragment. Conditions (a) NaBH(OAc)3 (b) Me2C(OMe)2, H+ (c) MeOH, H+ (d) AcCl, collidine (e) MEM Cl, N, iV-diisopropylethylamine. Pase = phosphatase.

Reaction of 1-morpholinocycloalkenes 16 (n = 3-8) with dimethyl(succinimido)sulfonium fluorosulfate ° gave an equimolar mixture of dimethyl(2-morpholinocyclohex-l-enyl)sul-fonium fluorosulfates 17 (n = 3-8) and succinimide. Addition of A,A-diisopropylamine to these mixtures in anhydrous acetonitrile at — 10°C gave in 36-60% yield colorless crystals which were shown to be pure e t/o-morpholino(succinimido)bicyclo[n.l.O]alkanes cis-lS (n = 3-8), on the basis of their HNMR, CNMR and IR spectra. If 17 (n = 8) is allowed to stand for 48 hours prior to addition of A.A -diisopropylethylamine, then 10% of cw-18 (n = 8)isaccompaniedby 39% ofthe trans-isomsr trans-lS n = 8). °Treatmentofthe isolated enaminosulfonium fluorosulfate 17 (n = 3) with succinimide in the presence of A,A-diiso-propylethylamine in anhydrous acetonitrile gave the same product. ... 

Pfaltz and coworkers [34] also found that varying the base had effects on the yield of the cyclohexenylation while enantiomeric excesses remained consistently high. Results of the base screen (Table 11.1) employing l,8-bis(dimethylamino)naphthaIene, 2,2,6,6-tetramethylpiperidine and A//-diisopropylethylamine showed that N,N-diisopropylethylamine was most successful. 

Gianneschi and coworkers [29] have utilized a similar approach in functionalizing ROMP copolymers with hydrophilic peptides. This work involves a block copolymer synthesis incorporating a phenyl NBE moiety as the hydrophobic block and an NHS moiety as the chemically addressable block. Subsequent conjugation of peptides via their N-termini affords amphiphilic block copolymers in which the hydrophilic shell is defined by a short peptide sequence programmed to be an enzyme substrate. For graft-to functionalization, A/ ,A/ -diisopropylethylamine was added to the activated ester diblock copolymer in DMF, followed by the addition of peptide (with respect to NHS units). 

An interesting phenomenon has been observed in the high pressure Diels-Alder reactions of the l-oxa[4.4.4]propella-5,7-diene (117) with 1,4-naphthoquinone, maleic anhydride and N-phenylmaleimide, where the diene 117 undergoes a rearrangement to the diene isomer 118 which, although thermodynamically less favored, exhibits a greater reactivity [40]. The reactivities of the three dienophiles differed since maleic anhydride and N-phenylmaleimide reacted only in the presence of diisopropylethylamine (DIEA) and camphorsulfonic acid (CSA), respectively (Scheme 5.15). The distribution of the adduct pairs shows that the oxygen atom does not exert a consistent oriental dominance on TT-facial selectivity. 

Fig. 29 Microwave-promoted multicomponent synthesis of polysubstituted thiophenes on soluble PEG support. Reagents and conditions a NCCH2OOH, DCC, DMAP, CHCI3, MW 130 W, 5 min b RCOCH2R, S8, diisopropylethylamine, MW 130 W, 15 min c R"COCl, di-isopropylethylamine, 0 °C to rt, 3 h d 1% KCN in CH3OH, o.n. R = H or alkyl R = alkyl or acyl R" = CH3, Ph...

Fig. 40 Microwave-assisted substitution of imidazole on C-2 in solid-phase. Reagents and conditions a benzaldehyde, N,N-diisopropylethylamine, CH2CI2, 24 h, rt b Nucleophile, TEA, Bp3Et20, THP, MW 120 °C, 5 min, closed vessel...

The Curtius rearrangement procedure described here is a modification of one reported by Winestock. The submitters have found this procedure to be considerably more reproducible when N,N-diisopropylethylamine is substituted for triethylamine. The procedure described for the preparation of trans-2,4-pentadienoic acid is a modification of an earlier one by Doebner. The submitters have found this method to give reproducibly higher yields, and to be more convenient, than other commonly used procedures for preparing this material. The use of dichloromethane as the extracting and crystallizing solvent greatly simplifies the isolation of polymer-free samples of the crystalline acid. 

Reactions of sulfoxides containing a- and /9-hydrogen atoms, for example n-dibutyl sulfoxide 1170, with trimethylsilyl iodide 17 in the presence of tertiary amines such as diisopropylethylamine (DIPEA) give, e.g., the vinylsulfide 1171 as an 1 1 E/Z mixture in 75% yield and HMDSO 7 [16] (Scheme 8.4). Analogously, the vinyl sulfoxide 1172 or the vinyl sulfoxide 1174 furnish the 1,3-dienyl sulfides 1173 and 1175 in 91 and 85% yield, respectively, and HMDSO 7 [16]. 

Treatment of the allylic sulfoxide 1227 a with diisopropylethylamine (DIPEA) or of 1227 b with N-trimethylsilyldiethylamine 146 and TMSOTf 20 leads in ca. 90% yield to the quaternary amino derivatives 1228 and 1229 and HMDSO 7 [36] (Scheme 8.15). Tetramethylene sulfoxide 1230 reacts with silylated thymine 1231 in the presence of three equivalents of TMSOTf 20 to give the 4 -thio-nucleoside analogue 1232 and HMDSO 7 [37]. Other silylated pyrimidine, pyridine, and purine bases react analogously with cyclic sulfoxides to give 4 -thio-nucleoside analogues [37, 37a, 38]. 

Full details on the phosphorylation of water and alcohols by 4-nitrophenyl dihydrogen phosphate and the NfC H ) - and N(CH3) -salts of its mono- and dianion have been published 146>. Phosphoryl group transfer from the monoanion and dianion is thought to proceed via the monomeric POf ion. Addition of the sterically unhindered amine quinuclidine to an acetonitrile solution containing the phosphate monoanion and tert-butanol produces t-butyl phosphate at a faster rate than does the addition of the more hindered diisopropylethylamine. This nucleophilic catalysis of the phosphorylation reaction is also explained by the intermediacy of the POf ion. 

For the preparation of N- 2-(methoxyphenyl)cthyl ]-4-mcthylbcn-zenesulfonamide (1) from Ameba resins A and Ba-Bd, 100 mg (0.089 mmol) Ameba resin A was added to a glass peptide reaction vessel, suspended in 3.0 mL 1,2-dichloroethane (DCE note 2), and treated with 26 pL (0.18 mmol, 2.0 Eq.) 2-(4-methoxy-phenyl)ethylamine (note 2) and 38 mg (0.178 mmol, 2.0 Eq.) sodium triacetoxyborohydride (note 2). The suspension was shaken for 1 h treated with 5 mL MeOH filtered on a glass frit and washed with DCM (2x5 mL), DMF (2x5 mL), MeOH (2 x 5 mL), and DCM (2x5 mL). The resin was dried under vacuum (0.5 torr) at room temperature overnight. The resin was suspended in 1.5 mL DCM, treated with 155 pL (0.89 mmol, 10.0 Eq.) N,N-diisopropylethylamine (note 2) and 85 mg (0.445 mmol, 5.0 Eq.) p-toluenesulfonyl chloride (note 2), and shaken for 3.5 h. The reaction mixture was filtered on a glass frit, washed with DCM (2 x 5 mL), DMF (2x5 mL), MeOH (2x5 mL), and DCM (2 x 5 mL), and dried under vacuum (0.5 torr) at room temperature for 2h. The resin was treated with 2.5 mL of a solution of 5% trifluoroacetic acid (note 2) in DCM, shaken for 15 min, filtered on a glass frit, and washed with DCM (3x5 mL). The combined filtrate and washings were concentrated and dried under vacuum (0.5 torr) at room temperature overnight to afford 18.0 mg (66%) N- [2-(methoxyphenyl)ethyl] -4-methylbenzenesulfonamide (1). 

Trimethylsilyl)acetylene was used as received from Aldrich Chemical Company, Inc. N,N-Diisopropylethylamine was distilled from calcium hydride (atmospheric pressure) and stored over 4 A molecular sieves under argon. 

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