Telomerization products

Chloro-2,2,3-trifluoropropionic acid has been prepared by permanganate oxidation of 3-chloro-2,2,3-trifluoropropanol which is one of the telomerization products of chlorotrifluoroethylene with methanol. The present procedure is a modification of one reported earlier and is undoubtedly the method of choice for making propionic acids containing 2 fluorine atoms, i.e., 2,2,3,3-tetrafluoropropionic acid, 3,3-dichloro-2,2-difluoropropionic acid, and 3-bromo-2,2,3-trifluoropropionic acid. When preparing 2,2,3,3-tetrafluoropropionic acid from tetrafluoroethylene, it is desirable to use an additional 50 ml. of acetonitrile and externally applied heat to initiate the reaction. 

In fact, the stereochemistry of the hydroamination seems to depend strongly on the experimental conditions. For example, for the condensation of Et2NH with 1,3-butadiene, either cis-l-diethylamino-2-butene (n-BuLi, CgHs-EtjO) [204, 205], or trans-l-diethylamino-2-butene (sec-BuLi, THF) [155] can be obtained in ca. 98% yield stereoselectivity. In some cases, telomerization products are also formed [205]. 

These occur readily between electron-rich alkenes and electron-poor carbonyl compounds. The first example, reported in 1959 (64HC(19-2)729), was the formation of 4,4-diaryloxetane-2,2-dicarbonitriles by the room temperature reaction of 1,1-diarylethylenes and carbonyl cyanide. Continued investigation of this reaction shows that a telomerization product is also formed, the tetraphenylpentadienedinitrile (55) from 1,1-diphenylethylene and carbonyl cyanide. This may be interpreted to indicate that carbon-carbon bond formation may commence somewhat ahead of carbon-oxygen bond formation (75MI51302). This... 

Trialkylamines are used as additives in the telomerization of butadiene and water in a two-phase system (103). The catalyst comprises a palladium salt and tppms or tppts. The amines may build cationic surfactants under catalytic conditions and be capable of micelle formation. The products include up to five telomerization products (alcohols, alkenes, and ethers), and thus the reaction is nonselective. 

Generally, octatriene formation is favored by higher temperatures, higher phosphine and/or butadiene concentrations and, importantly, by an increase in steric bulk of either the ligand or the nucleophile. Indeed, Harkal et al. showed a selectivity switch from telomerization products to 1,3,7-octatriene formation by altering the steric demand of the /V-heterocyclic carbene ligand in the reaction of butadiene with isopropanol under further identical reaction conditions [48]. For the more basic nucleophiles, such as the alcohols, the telomer products are stable under experimental conditions, i.e. product formation is irreversible, but for more acidic substrates such as phenol, product formation is reversible and more 1,3,7-octatriene will be formed after the substrate has been depleted. 

Behr et al. [114] investigated the selective formation of octadienyl phenol ethers in a liquid-liquid biphasic loop reactor. Although the Pd/TPPTS system showed good activity and selectivity (86% conversion with 74% selectivity towards the telomer after 5 h) in a lab-scale batch reactor, telomer yields in the loop reactor were insufficient for efficient phase separation. Telomerization with phenol was therefore deemed unsuitable for this type of reactor. The authors also noted that the C-allylated octadienyl phenol product rather than the telomerization product became the main product after 6 h of reaction, attributing this to a metal-catalyzed Claisen-type rearrangement. 

In fact, alkylated succinamides were isolated in some cases, though in very poor yields, and result from radical combination, which is a chain termination step. The experimental observations, i.e. the formation of (a) 1 1 adducts, (b) telomeric products, (c) alkylated succinamides, and (d) oxamide (when an olefin is absent), are consistent with a free radical mechanism. The telomeric products obtained support the assumption that we deal here with a chain reaction, because they are characteristic products of this type of reaction. Another proof for the chain reaction mechanism is the fact that when benzophenone is used as a photoinitiator (vide infra), the amount of benzpinacol formed is smaller than the amount of the 1 1 addition product of formamide and olefin (16). Quantum yield determinations will supply extra evidence for the validity of a chain reaction mechanism for this photoaddition reaction. 

As previous reactions have already shown, this reaction seems to be a free radical chain reaction. The experimental evidence so far available for such a mechanism is the following (a) the formation of dehydrodimers in the absence of an olefin (b) the formation of the anti-Mar-kovnikov 1 1 adduct as the major product when a terminal olefin is employed as the addend, and (c) the telomeric products obtained. Thus, reaction sequence can be summarized as follows ... 

In 1995, Porter et al. [34] reported the first excellent results for free radical addition to an electron-deficient alkene by use of chiral zinc complexes. Reaction of the oxa-zolidinone 9 with tert-butyl iodide and allyltributylstannane 30 in the presence of Zn(OTf)2 and a chiral bis(oxazoline) ligand 12 gave the adduct 44 in 92 % yield with 90 % ee (Sch. 18). The chiral bis(oxazoline) complexes derived from ZnCl2 or Mg(OTf)2 gave racemic products. In this reaction, lower allyltin/alkene ratios gave substantially more telomeric products, and a [3 + 2] adduct 45 of the oxazolidinone 9 and the allylstannane 30 was obtained at temperatures above 0 °C. 

Palladium-catalyzed 1,4-hydroamination of conjugated dienes is usually accompanied by large amounts of 2 1 telomerization product [21,22]. It was shown that the use of an amine hydrochloride as a cocatalyst increased the selectivity for the 1,4-hydroamination product [23]. Thus, 1,3-butadiene and 2-3-dimethylbuta-1,3-diene gave a fair yield in the palladium-catalyzed 1,4-amination shown in [Eq.(5)]. 

It was also demonstrated that organosilylstannanes can be used as the trimethylsilyl anion source. In this case, the acid chlorides gave poor results and it was found that aryl iodides were suitable substrates. Reaction of buta-1,3-diene with Phi and BujSnSiMej gave the 1,4-carbosilylation product in 50% yield as an E/Z 84 16 mixture. The use of phenyl triflate as the aryl source did not give the desired 1,4-addition product but afforded the 2 1 telomerization product from two molecules of diene and one trimethylsilyl group, in good yield. 

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

In a related study, Trost and Zhi [24] showed that the use of dppp(l,3-(diphenylphosphino)propane) as a ligand on palladium also led to a high selectivity for 1,4-addition of active methylene compounds to 1,3-dienes. For example, 2,3-dimethylbuta-1,3-diene gave an excellent yield with a number of active methylene compounds [Eq.(9)]. Interestingly, the reaction temperature is of importance for the 1,4-selectivity. Thus, in the reaction of (PhSOjICHa with isoprene employing the Pd(0)-dppp system, the ratio between the desired 1,4-addition product and the telomerization product was 73 27 at 70 °C but increased to 95 5 at 100 °C. Also, cyclic dienes gave an excellent yield of the 1,4-addition products [Eq.(lO)]. 

Butadiene is a very inexpensive and attractive molecule for the industrial chemist. Several products can be made from butadiene and carbon monoxide under specific conditions. Subtle effects control the outcome of palladium-catalyzed carboxyla-tion of conjugated dienes such as butadiene. Depending on the reaction conditions, monocarboxylate, dicarboxylate, or telomerized products could be obtained (Scheme 4, cf. Section 2.3.5). 

Transition metal carbohalogenation with polyhalomethanes can also be applied to non-conjugated dienes, leading to formal telomerization products. In an early example, this reaction was applied to the addition of carbon tetrachloride to norbornadiene, mediated by pentacar-bonyliron and trimethylamine iV-oxide. Stereoisomeric nortricylane products 12 were obtained with moderate stereoselectivity31-32. 

Figure I. Distribution of telomeric products obtained from ethylene and benzene at 110°C...

That even vinylic and allylic positions can be metalated by lithium from an amine complex is evident from the nature of the ethylene telomerization products formed in the presence of higher olefins (15). In the presence of excess butene, telomers are formed that vary in structure depending on the nature of the butene isomer (Table VII). Telomeric... 

Fluorinated alkenes are able to insert into weak C-H bonds of various compounds branched alkanes, haloforms, alcohols, ethers, aldehydes and their corresponding ketals. These reactions usually involve the use of UV irradiation or radical-initiation catalysts, such as peroxides or azobisisonitriles. Variable amounts of telomeric products are also formed. Under the influence of /-irradiation (60Co source), one-to-one adducts are obtained predominantly. Attack of the intermediate radical occurs preferentially on the less-hindered carbon of the fluorinated alkenc. 

In the thermal addition, telomerization intervenes, even though only to a small extent. An appreciable amount of telomerization products is obtained if an excess of olefin is used at high pressure e.g., SiHCl3 and an excess of ethylene at 285°/200 atm give products of the composition SiCl3— (CH2CH2) —H where n = 1-5 331 and CH3SiHCl2 with an excess of ethylene or propene at 260-270° and an initial pressure of 560 atm afford telomers... 

Telomerase activity is typically measured using the Telomeric Repeat Amplification Protocol (TRAP) assay. In the TRAP assay, products of the telomerase reaction are quantified following their PCR amplification [20, 21], The assay is exquisitely sensitive and incorporates an internal standard (ITAS) with which to normalize signals for differences in PCR efficiency. Telomerase activity is calculated as the ratio of the intensity of the telomeric products to that of the ITAS. With this assay, telomerase activity can be measured in a wide range of specimens, from tissue biopsies to cell pellets [22]. High throughput assays have been developed to adapt the telomerase assay to the clinical environment. Many of these new assays take advantage of fluorophores that alleviate the use of radioisotopes and facilitate the quantification of PCR products. 

The palladium(O)-catalyzed reaction of 1,3-dienes with active methylene compounds to give 1,4-addition of a hydrogen atom and a stabilized carbanion is complicated by the formation of 2 1 telomerization products [27]. It was found by Hata et al. [21a] that bidentate phosphines such as l,2-(diphenylphosphino)ethane favor formation of the 1 1 adduct. More recent studies by Jolly have shown that the use of more a-donating bidentate phosphines on palladium gave a high selectivity for 1 1 adducts [23]. For example, 1,3-butadiene reacted with 11 to give the 1,4-addition product 12 in 82% yield, along with 18% of the 1,2-addition product 13 (Eq. (7)). 

Dow Chemical Company operates a 1-octene plant in Tarragona, Spain, in which butadiene is reacted with methanol (2 1 molar ratio) in a homogeneous, Pd-catalyzed telomerization reaction. 1-Octene is formed after hydrogenation of the initial telomerization product by abstraction of methanol (van Leeuwen et al, 2010). 

The MWDs of unmodified oligobutadienes range between 1000 and 8000 Da and exhibit different microstructures materialized through cis-1,4 or trans-1,4 as well as through vinyl structures. Molecular weight distribution is influenced by the method of synthesis. The procedure of live polymerization forms products with narrower MWD, and that of telomerization, products with broader MWD [41]. Oligobutadienes can be easily functionalized so that a wide range of compounds with various applications is obtained [42]. 

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