Triisopropylsilyl-substituted

The a-aryl-p-triisopropylsilyl-substituted vinyl cations 1-3 are generated by protonation of the corresponding l-aryl-2-silyl-alkynes with superacids at low temperatures (Eq. 1). For die protonation of a-ferrocenyl-p-(triisopropyl)silylethyne to yield the l-ferrocenyl-2-(triisopropyl)silylvinyl cation 4 the weaker acid CF3COOH is sufficient (Eq. 2). 

The two examples shown in Scheme 2.57 illustrate that the metaUotropic shift depends on the nature of the substituent on the 1,3-diyne [33bj. When the substrates 164 and 166 were subjected to 1-octene in the presence of catalyst 2, an initial enyne CM occurred followed by cychzation to give a ruthenium alldnyl carbene intermediate. Termination by CM with the co-olefin after metaUotropic [l,3]-shift was observed for the benzyloxymethyl substituent with production of 165, whereas termination at the sterically less substituted carbon deUvered the complementary regioisomer 167 in case of triisopropylsilyl substitution. 

Soderquist and coworkers have reported [19] that hydroboration with 9-BBN of 1-silylacetylenes, having bulkier groups on the Si, place the boron exclusively at the internal position of the alkyne as a kinetically less preferred process. Consequently, triisopropylsilyl-substituted alkynes afford the novel P-silylated vinyl-boranes, which on oxidation with alkaline hydrogen peroxide affords the corresponding ketones (Eq. 7.11) in excellent yields, a truly noteworthy example of the stability imparted to this functionality by the triisopropyl substitution on silicon [20]. It should be noted that earlier studies have shown failures to obtain (3-ketosilanes from suitable organoprecursors due to their known sensitivity to bases and nucleophiles [21]. 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

GABA HMG-CoA HMPA HT LDA LHMDS LTMP NADH NBH NBS NCS NIS NK NMP PMB PPA RaNi Red-Al RNA SEM SnAt TBAF TBDMS TBS Tf TFA TFP THF TIPS TMEDA TMG TMP TMS Tol-BINAP TTF y-aminobutyric acid hydroxymethylglutaryl coenzyme A hexamethylphosphoric triamide hydroxytryptamine (serotonin) lithium diisopropylamide lithium hexamethyldisilazane lithium 2,2,6,6-tetramethylpiperidine reduced nicotinamide adenine dinucleotide l,3-dibromo-5,5-dimethylhydantoin A-bromosuccinimide A-chlorosuccinimide A-iodosuccinimide neurokinin 1 -methyl-2-pyrrolidinone para-methoxybenzyl polyphosphoric acid Raney Nickel sodium bis(2-methoxyethoxy)aluminum hydride ribonucleic acid 2-(trimethylsilyl)ethoxymethyl nucleophilic substitution on an aromatic ring tetrabutylammonium fluoride tert-butyldimcthyisilyl fert-butyldimethylsilyl trifluoromethanesulfonyl (triflyl) trifluoroacetic acid tri-o-furylphosphine tetrahydrofuran triisopropylsilyl A, N,N ,N -tetramethy lethylenediamine tetramethyl guanidine tetramethylpiperidine trimethylsilyl 2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl tetrathiafulvalene... 

Acetoxylation. Although furans are readily oxidized, furans substituted by a triisopropylsilyl (TIPS) group when treated with DDQ in toluene-acetic acid at 0° undergo acetoxylation at an adjacent a-methylene group.3... 

The ferrocenyl group is a very good electron donor. The a-ferrocenyl P-silyl substituted carbocation 20 is accessible by protonation of ( )-1 -ferrocenyl-2-(triisopropylsilyl)alkene 21 with trifluoroacetic acid in SO2CIF at - 95 °C (13, 22). 

Lithiation can be diverted away from C-2 of indole by the use of a bulky N-substituent. Although 1-methylgramine is cleanly lithiated at C-2, l-(triisopropylsilyl)gramine is lithiated selectively at C-4 and can lead to useful 4-substituted indoles electrophiles include 1,2-dibromoethane, DMF, and diphenyl sulfide (Scheme 60) (93H(36)29). 

Sterically controlled regioselective para-substitution of aniline has been achieved by introduction of sterically demanding l-isopropyl-2-methylpropyl or triisopropylsilyl groups at the nitrogen of aniline using a lithiation-substitution sequence.71... 

An efficient procedure for the nucleophilic displacement of the A, A -dimethylamino group of 1-triisopropylsilyl-gramines via the fluoride ion-induced elimination-addition reaction has been devised. 1-Triisopropylsilylgramine methiodide 1371 reacted smoothly with a variety of nucleophiles in the presence of tetrabutylammonium fluoride (TBAF) to give 3-substituted indoles 1372 (Scheme 262) <1995TL5929>. 

Reactions of pyrrole or 1-methylpyrrole with N-aroylbenzotriazoles (ArCO = 4-MeCgH4CO, 4-O2NC6H4CO, 4-Et2NC6H4CO, 2-furoyl, 2-pyridoyl, 2-indolcarbonyl, 2-pyrroloyl) in the presence of TiCU afford 2-acylpyrroles in yields from 21% to 94%. In contrast, l-(triisopropylsilyl) pyrrole under the same conditions gives the corresponding 3-acyl-substituted pyrroles (03JOC5720). 

Heating of bis(trimethylstannyl)carbodiimide with triisopropylchlorosilane results in a stepwise replacement of the trimethylsilyl groups. Also, reaction of this carbodiimide with two equivalents of trimethylchlorosilane affords bis(trimethylsilyl)carbodiimide (85 % yield), and with tributylchlorostannane, bis(tributylstannyl)carbodiimide (90 % yield) is obtained. N-triisopropylsilyl-N -trimethylstannylcarbodiimide 21 reacts with bis(diisopropylamino)chlorophosphane to give the Si, P substituted carbodiimide 22." ... 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

Treatment of triisopropylsilyl enol ethers of cyclic ketones with ammonium cerium nitrate (3 equiv) and sodium azide (4.5 equiv) in acetonitrile at — 20 °C gave a-azido ketones in good yields124. By varying the ratio of the reagents the yields were lower or the formation of byproducts, difficult to separate, increased. Mixture of diastereomers (ratio not reported) were generally obtained from substituted substrates, except from the bicyclic ketones 16. 

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