3- Methyl-4-bromo-5-trimethylsilyl

Somei adapted this chemistry to syntheses of (+)-norchanoclavine-I, ( )-chanoclavine-I, ( )-isochanoclavine-I, ( )-agroclavine, and related indoles [243-245, 248]. Extension of this Heck reaction to 7-iodoindoline and 2-methyl-3-buten-2-ol led to a synthesis of the alkaloid annonidine A [247]. In contrast to the uneventful Heck chemistry of allylic alcohols with 4-haloindoles, reaction of thallated indole 186 with 2-methyl-4-trimethylsilyl-3-butyn-2-ol affords an unusual l-oxa-2-sila-3-cyclopentene indole product [249]. Hegedus was also an early pioneer in exploring Heck reactions of haloindoles [250-252], Thus, reaction of 4-bromo-l-(4-toluenesulfonyl)indole (11) under Heck conditions affords 4-substituted indoles 222 [250], Murakami described the same reaction with ethyl acrylate [83], and 2-iodo-5-(and 7-) azaindoles undergo a Heck reaction with methyl acrylate [19]. 

Less success has been obtained with removable N-substituents, however, the trityl and THP derivatives of 4-bromopyrazole both giving low yields of products derived from reaction of the lithio derivatives with carbonyl compounds [62CB222 82ACS(B)101]. Magnesium metal has also been used to produce l-methyl-4-(trimethylsilyl)pyrazole by an in situ Grignard reaction on the analogous 4-bromo compound in HMPT (84JOC4687). 

One of the classical solutions to overcome the low reactivity is to render the carbomagnesiation intramolecular. For example, Utimoto and coworkers reported that the reaction of ( )-6-bromo-3-methyl-l-trimethylsilyl-l-hexene (85) with magnesium produces the corresponding Grignard reagent 86, which intramolecularly adds to the vinylsilane moiety from the less hindered side affording a single stereoisomer of cycUzed product 87 (Scheme 60) °°. 

Intermolecular carbometallations are typically accomplished with organolithiums however, dia-stereocontrolled intramolecular carbometallation can be attained with appropriate Grignard reagents, as exemplified in Scheme 88, the suprafacial and 5-exo-trig closure of ( )-6-bromo-3-methyl-1 -trimethylsi-lyl-1-hexene (267) to fraru-l-methyl-2-(trimethylsilyl)methylcyclopentane (268).203... 

Method D (equation 37) is neither a convenient nor an effective way to generate 3a. After heating bis[bromo(trimethylsilyl)methyl]mercury for 7 days at 160 °C with cyclohexene and diphenylmercury, 7-trimethylsilylbicyclo[4.1.0]heptane was obtained in a yield of only 9%, accompanied by a trace of the carbene dimers (cis- and trans-bis(trimethylsilyl)ethene) and a large amount of starting material75. 

Application of Zr-catalyzed carboalumination to haloalkyl-substituted l-(tri-methylsilyl)-l-alkynes provides a new metal-promoted cyclization reaction [102]. The reaction of 4-bromo-3-methyl-l-(trimethylsilyl)-l-butyne (104) and its regioisomer 105 with Cp2ZrCl2-Me3Al furnished the same product, 106. The regiochemical results are in good agreement with the participation of intermediate 107, as indicated in Sch. 70. 

On the other hand, bis[bromo(trimethylsilyl)methyl]mercury is very stable thermally. After heating for 7 days at 160 C in the presence of cyclohexene, only 9% of cxo-7-trimethylsilyl-bicyclo[4.1.0]heptane (4) could be isolated, and large amounts of the starting material were recovered. ... 

Another application of the stereoselective tandem cyelization is the synthesis of isoiri-domyrmecin from an acyclic precursor97. Reductive cyelization of 4-bromo-5-methyl-l-trimethylsilyl-8-decen-l-yne gives a mixture of four bicyclic products in a ratio of 47 44 5 4. Conversion to the bicyclic ketone, an intermediate in the synthesis of isoiridomyrmecin, shows the potential utility of this approach in natural product synthesis. 

Bromo(trimethylsilyl)mefhyl]-N.N-diisopropylbeiizaiiiide (13) Typical Procedure l l JV,N-Diisopropyl-2-[(trimethylsilyl)methyl benzamide (12 1.14 g, 3.9 mmol) in CCI4 (200 ml) (CAUTION) was added to NBS (1.01 g, 5.0 mmol) and benzoyl peroxide (10 mg). The mixture was heated under reflux and irradiated by a UV sun lamp for 90 min. The mixture was cooled to rt and the succinimide removed by filtration through Celite. The filtrate was concentrated under reduced pressure to give a crude oil. The crude product was purified by chromatography (silica gel) to give the a-bromosilane 13 as a white solid after recrystallization (pentane) yield 1.14 g (79%) mp 89-90 °C. 

Tocopheryl)propionic acid (50) is one of the rare examples that the o-QM 3 is involved in a direct synthesis rather than as a nonintentionally used intermediate or byproduct. ZnCl2-catalyzed, inverse hetero-Diels-Alder reaction between ortho-qui-none methide 3 and an excess of <2-methyl-C,<9-bis-(trimethylsilyl)ketene acetal provided the acid in fair yields (Fig. 6.37).67 The o-QM 3 was prepared in situ by thermal degradation of 5a-bromo-a-tocopherol (46). The primary cyclization product, an ortho-ester derivative, was not isolated, but immediately hydrolyzed to methyl 3-(5-tocopheryl)-2-trimethylsilyl-propionate, subsequently desilylated, and finally hydrolyzed into 50. 

Capillary gas chromatography is conducted with a cross-linked phenyl methyl silicone stationary phase (5%, 25 m x 0.2 mm x 0.5 pm film thickness, injector temp. 225°C, detector temp. 250°C, column temp. 40-200°C, 15°C/min after 1 min initial time). (Z)-2-Bromo-5-(trimethylsilyl)-2-penten-4-ynoic acid ethyl ester is observed to have a retention time of 14.0 min. GC data for bis(trimethylsilyl)butadiyne is as follows retention time 10.0 min, response factor (GC area produced relative to an equimolar quantity of (Z)-2-bromo-5-(trimethylsilyl)-2-penten-4-ynoic acid ethyl ester) 1.29. For (E)-2-[(trimethylsilyl)ethynyl]-5-(trimethylsilyl)-2-penten-4-ynoic acid ethyl ester the retention time is 17.0 min, the response factor 1.19. 

The reaction of ethyl A-arylcarbamates 3 with l-bromo-3,3-dimethyl-2-buta-none or l-bromo-3-ethyl-3-methyl-2-pentanone 4 in the presence of lithium bis(trimethylsilyl)amide (LiHMDS) results in the one-step synthesis of 3-aryl-5-ferf-butyl-2(3/T)-oxazolones 7 in fair to good yields (Fig. 5.2 Table 5.1, Fig. 5.3). This method is efficient for the preparation of bulky 5-substimted-2(37f)-oxazo-lones. 

Enol lactones with a halogen at the vinylic position have been synthesized as potential mechanism-based inactivators of serine hydrolyases <81JA5459). 5-Hexynoic acids (181) can be cyclized with mercury(II) ion catalysis to y-methylenebutyrolactones (182) (Scheme 41). Cyclization of the 6-bromo and 6-chloro analogues leads stereospecifically to the (Z)-haloenol lactones (trans addition) but is quite slow. Cyclization of unsubstituted or 6-methyl or 6-trimethylsilyl substituted 5-hexynoic acids is more rapid but alkene isomerization occurs during the reaction. Direct halolactonization of the 5-hexynoic acids with bromine or iodine in a two-phase system with phase transfer catalysis was successful in the preparation of various 5-halomethylene- or 5-haloethylidene-2-phenylbutyrolactones and 6-bromo-and iodo-methylenevalerolactones (Scheme 42). 

Michael additions. Gerlach and Kiinzler report that the lithium enolate of S-t-butyl thioacetate undergoes 1,4-addition to cyclopentenone. They have extended this Michael reaction to a synthesis of methyl jasmonate (5), based on the similar conjugate addition of the trimethylsilyl enolate 1 promoted by tetra-n-butylam-monium fluoride. The adduct 2 was alkylated by l-bromo-2-pentyne in the presence of tetra-n-butylammonium fluoride to give 3 in rather low yield. Remaining steps to 5 were methanolysis and partial hydrogenation of the triple bond. 

The thermal decomposition of bis[dibromo(trimethylsilyl)methyl]mercury in the presence of diphenylmercury occurs more easily than for the chloro analogs. However, 1-bromo-l-trimethylsilylcyclopropanes 3, which are formed in the presence of cyclohexene, are thermally less stable and partially decompose under the reaction conditions. ... 

Formation of a C-H and a C-C bond at the expense of a C-Br and a C-Si bond occurs when 1 -bromo -1 -trimethylsilylcyclopropanes are treated successively with butyllithium and dichloro-methyl methyl ether at — 95°C and yield cyclopropyl trimethylsilyl ketones The 1-... 

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