TIPS moiety

With this key union effected, only a few operations separated 48 from the substrate needed to test enyne metathesis (i.e. 12, Scheme 9). First, the controlled exposure of this compound (48) to 2 equivalents of TBAF in THF at 0°C effected the lysis of both the phenolic silyl ether and the TMS group append onto the terminal position of the alkyne, but, importantly, not the TIPS group on the other acetylene group. As such, in the next operation partial reduction with Lindlar s catalyst (Pd on BaS04 poisoned with quinoline) was accomplished selectively on only one alkyne to provide the needed terminal olefin. Finally, cleavage of the alky-nyl TIPS moiety under more forcing conditions (TBAF, THF, 25 °C), followed by silylation of both the allylic hydroxy and the phenolic groups (TBSCl, imid, DMF), then completed the assembly of enyne metathesis precursor 12 in 62% overall yield from 48. 

An extension to this protocol is the concept of orthogonality allowing for the selective removal of one PG in the presence of another PG. For example, in the synthesis of oligo(para-phenyleneethynylene) rods by Godt et al. [128], the hydroxymethyl (HOM) and TIPS moieties in 35 were independently removed by treatment either with MnOj and KOH to give 36 in 86% yield or with TBAF to afford 37 in 96% yield, respectively (Scheme 9.12). 

Cyclization of the A -TIPS protected pyrrolohydroxylactam 163 (where n = 1 and Ri = alkyl, H), activated by 2 equiv TMSCl in TBME at -55 °C to -30 °C, gave a racemic 1.5-3 1 mixture of the C-4 (165) versus C-2 cyclization product (168), regardless of whether Ri was substituted with H or alkyl. Cyclization at C-2 was unexpected since the A -TIPS moiety effectively shields the N-, C-2 and C-5 positions. Coaddition of 20 mol % of Jacobsen chiral thiourea catalyst 152 to 163 under the same reaction condition, afforded the desired C-4 adduct 168 in good yield (49-77%) and excellent enantiomeric purity (92-96% ee). Evidently co-complexation of the organocatalyst to the A -acylimminium ion derived from 163, provided an effective discriminating spatial environment. 

Another spectacular result attributable to the TIPS group is seen in the carefully engineered oxazaborolidine 81-catalyzed (0.05 equiv) catecholborane (82) reduction of methyl acetylenic ketones 83 and 84. In this study, Helal, Magriotis, and Corey conclusively demonstrated that the distal acetylenic TIPS moiety was responsible for catalyzed delivery of the activated hydride essentially only from the indicated ketone lone pair (eq 20). ... 

The binding site is located at the tip of the subunit within the jelly roll structure (Figure 5.23). The sialic acid moiety of the hemagglutinin inhibitors binds in the center of a broad pocket on the surface of the barrel (Figure 5.24). In addition to this groove there is a hydrophobic channel that can accomodate large hydrophobic substituents at the C2 position of sialic acid (Figures 5.22 and 5.24). 

Subsequently, these catalysts were evaluated in the enantioselective desymmetri-sation of achiral trienes, and three distinct trends in catalyst selectivity were found. Firstly, catalysts 56a-b with two phenyl moieties on the backbone of the A -heterocycle exhibited higher enantioselectivity than those with a fused cyclohexyl group as the backbone 55a-b. Secondly, mono-ort/io-substituted aryl side chains induced greater enantioselectivity than symmetrical mesityl wing tips. Thirdly, changing the halide ligands from Cl to I" increased the enantioselectivity. As a result, catalyst 56b turned out to be the most effective. For example, 56b in the presence of Nal was able to promote the desymmetrisation of 57 to give chiral dihydrofuran 58 in up to 82% conversion and 90% ee (Scheme 3.3). 

This model of the receptor-bound conformation of TIP is characterized by a clustered configuration of the three aromatic moieties with the Phe3 aromatic ring sandwiched between the Tyr1 and Tic2 aromatic rings. 

We have also examined the behavior of copolymers of o-tolyl vinyl ketone and methyl vinyl ketone (CoMT). In this case the light is absorbed exclusively at the aromatic carbonyl chromophore and the reaction proceeds from this site, while the methyl vinyl ketone moieties provide a relatively constant environment but prevent energy migration along the chain. The values of Tg and Tip in benzene have been included in Table II. These copolymers axe also soluble in some polar solvents for example, we have used a mixture of acetonitrile acetone methanol (30 30 Uo, referred to as AAM). This mixture is also a good solvent for the electron acceptor paraquat (PQ++) which has been shown to be good biradical trap in a number of other systems (9.). 

Takasu, Ihara and coworkers described an efficient synthesis of ( )-paesslerin A (4-73) using a combination of a [4+2] and a [2+2] cycloaddition (Scheme 4.16) [25], Reaction of 4-71 and propargylic acid methyl ester in the presence of the Lewis acid EtAlCl2 led to 4-72 in 92 % yield, which was converted in six steps into the desired natural product 4-73 by transformation of one of the ester moieties into a methyl group, hydrogenation of one double bond, removal of the other ester moiety, and exchange of the TIPS group for an acetate. 

The results demonstrated that both compression and shear can induce the formation of C-C bonds between sp-hybridized carbons atoms, which leads to polymerization within the SAM. Interestingly, it was found that the location of these reactive sites within the film could influence the calculated friction. For instance, if the diacetylene components in the chains were close to the tip/film interface, reactions between the film and tip could occur, which led to wear and high friction. On the other hand, if the diacetylene moieties were far from the tip, the reactions did not lead to wear and had little effect on the average calculated friction. These observations demonstrate that a proper treatment of the chemical reactivity of the system may be necessary in some cases to calculate friction accurately. 

In biomedical applications, the ranges of ion concentration are higher by several orders of magnitude. For instance, the abovementioned calcium probes for living cells cannot be used because the dissociation constant is so low that they would be saturated. Special attention is thus to be paid to the ionophore moiety to achieve proper selectivity and efficiency of binding. For instance, at present there is a need for a selective fluorescent probe for the determination of calcium in blood which could work in the millimolar range in aqueous solutions so that optodes with immobilized probes on the tip could be made for continuous monitoring calcium in blood vessels. 

In accordance with the H and NMR parameters, the heterocyclic moiety of the -substituted (R = Me, Et, Ph, p-MeQH4, P-CIC6H4) diendo- and diexo-fused 4-oxo-4a,5,6,7,8,8a-hexahydro-lH- and -4a,5,8,8a-tetrahydro-lH-5,8-methanoquinazoline-2-thiones 353 assumes a distorted sofa conformation in which the N(l) —C(=S) —N(3) grouping forms the tip of the sofa [85JCS(P1)2483]. 

Table II highlights the 3C NMR relaxation times that reflect molecular motions and help define the physical properties of the cutin polymer. For those solid-like carbons that cross polarized, considerable motional freedom was evidenced for (CH2)n and CH2OCOR groups, on both MHz and kHz timescales, by the short values of Tj(C) and Tip(C), respectively. By contrast, the CHOCOR moiety was more restricted dynamically as judged from its long value of TX(C) low-frequency motions in particular were implicated by the strong dependence of Tip(C) on Bi. These latter groups...

Lately one has been able to encounter experimental studies more frequently denoted Chemical Force Microscopy , CMF. This includes various attempts to observe tip-surface interactions which are specific to the chemical constitution of the surface. Mostly, CFM involves modification of the tip by a surface layer with molecules which contain particular functional groups, i.e. hydrophilic or hydro-phobic moieties, hydrogen bonding groups, ionic substituents and molecular units which can undergo electron-donor-acceptor interactions. However, sometimes the term Chemical Force Microscopy is just used for any method which can provide a material specific contrast. Depending on the specificity, CFM provides valuable information on the nanoscale composition complementary to other surface characterisation methods which are sensitive to the chemical con-... 

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