Proximal unsaturation

Palladium-catalyzed Cross-coupling Involving Alkyl Groups without Proximal Unsaturation... 

The facts shown above indicate that /3,y-unsaturated halides and other electrophiles are some of the most reactive classes of compounds.t Although generally less reactive, a,/3-unsaturated derivatives are also generally reactive and practically useM. i On the other hand, simple alkyl halides lacking a proximal unsaturation are generally insuffi-ciendy reactive. Relatively little is known about the effects of more remote Tr-bonds and of proximal n-electron donors, but the results observed for ( )-2-methyl-l,4-diiodo-l-butene shown in Scheme 2 of Sect. 1.2 clearly indicate that homoallyl halides must be far less reactive than alkenyl hahdes. These results collectively point to the probable significance of prior 7r-complexation as a binding process and probable subsequent intramolecular interaction of Pd with C—bonds. 

It will be recalled that one of the key operations in the synthesis of IJK ring system 86 is the intramolecular conjugate addition reaction (see 90—>89, Scheme 17b) to form ring J. In the context of compound 90, the electrophilic a,/ -unsaturated ester moiety and the potentially nucleophilic tertiary hydroxyl group reside in proximal regions of space, a circumstance that would seem to favor the desired cyclization evept (see Scheme 19). Indeed, exposure of a solution of 90 in THFto sodium hydride (1 equiv.) for one hour at 25 °C results in the formation of compound 89 in 92% yield. In... 

Compounds with cis double bonds in the side chain were in general found to be more potent and efficacious than their triple-bond congeners, both in in vivo and in in vitro functional assays [98, 106, 107]. QSAR models have been generated for the compounds with unsaturated [108] and l, l -dimethyl [96] side chains to determine more precisely the pharmacophoric requirements of the receptor. It is postulated that for optimum potency, the side chain must be of a suitable length and flexibility to have the ability to loop back so that its terminus is in proximity to the phenolic ring. The widely used, potency enhancing 1 - and 2 -methyl substituents would be expected to increase the tendency of the side chain to adopt a looped back, rather than an extended conformation. 

When looking at the different classes of CF2 compounds, those bound to saturated and unsaturated carbon, those bound to hydrogen, and those bound to heteroatoms and proximate to functional groups, it will be seen that there are predictable trends in chemical shifts. 

Oxygen-free reactions of psoralens, when in close proximity to the target, proceed via the first excited states in which the 3,4-and the 4, 5 7r-bonds of the pyrone and furan moieties, respectively, can undergo C4-cyclization reactions with, e.g., unsaturated bonds of lipids, or the C5=C6 double bonds of thymine in DNA. In reactions with DNA the psoralen is believed to intercalate with DNA in the dark. Subsequent irradiation at 400 nm usually leads to furan-side 4, 5 -monoadduct formation, whereas irradiation at 350 nm increases the formation of crosslinks in which the furan and pyrone rings form C4 cycloadducts to thymines on opposite strands [95], Subsequent irradiation of the 4, 5 -monoadducts at 350 nm leads to formation of crosslinks and conversion into pyrone-side 3,4-monoadducts. Shorter wave-... 

Another factor affecting the lifetime of a membrane fluorophore probe is its proximity to the surface. The lifetimes of the DPH, DPH-phosphatidyl-choline (DPH-PC), and trimethylammonium-DPH (TMA-DPH) probes decrease in the order DPH > DPH-PC > TMA-DPH, as the probe locates nearer to the surface of the lipid bilayer.(7) The same is found for the anthroyl-stearate probes.(8) More recently, it has been shown that with TMA-DPH, the lifetime appears to be fairly sensitive to the differences in lipid bilayer packing induced by differing degrees of unsaturation in the phospholipid fatty acyl chains.(9) This aspect of the use of TMA-DPH and possibly other probes remains to be further exploited. 

Pandey and co-workers developed two photosystems useful for initiating one-electron reductive chemistry and applied them to activate a, 3-unsaturated ketones. The resulting carbon-centered radicals cyclize stereoselectively with proximate olefins. Their concept involved a secondary and dark electron transfer from... 

The cis-syn thymine dimer from DNA is believed to be formed from intra-strand dimerization of adjacent thymine residues. Photoaddition of two unsaturated molecules in the solid state can arise only if they are initially located in proximity in the crystal lattice [545, 546]. The formation of interstrand dimers would require gross distortion of the helical structure of DNA in order for the bases to approach the limiting distance (c. 4 A.) Hence, such dimers would be formed in only very small amount. However, the composition of the photoproducts may differ under varying experimental conditions [547-550]. 

Miscellaneous Iminium Catalyzed Transformations The enantioselective construction of three-membered hetero- or carbocyclic ring systems is an important objective for practitioners of chemical synthesis in academic and industrial settings. To date, important advances have been made in the iminium activation realm, which enable asymmetric entry to a-formyl cyclopropanes and epoxides. In terms of cyclopropane synthesis, a new class of iminium catalyst has been introduced, providing the enantioselective stepwise [2 + 1] union of sulfonium ylides and ot,p-unsaturated aldehydes.As shown in Scheme 11.6a, the zwitterionic hydro-indoline-derived catalyst (19) enables both iminium geometry control and directed electrostatic activation of sulfonium ylides in proximity to the incipient iminium reaction partner. This combination of geometric and stereoelectronic effects has been proposed as being essential for enantio- and diastereocontrol in forming two of the three cyclopropyl bonds. 

One of the most widely applied cycloaddition techniques for the preparation of thietanes is the reaction of sulfenes with enamines. The stereochemistry of these reactions has been extensively investigated by Truce and Rach. Whether the mechanism is a two-step or a concerted process, both in accordance with the stereoselective formation of the cis form in Scheme 1, is still unresolved. The special orientation of the 1,4-dipolar intermediate 64, in which the charged phenyl and dimethylamino moieties are in proximity, enforces the cis geometry of the resulting thietane dioxide. In the concerted mode of reaction, formation of the orthogonal oriented unsaturated system, 65 should also yield the cis cycloadduct. 

In some cases unsaturated groups (carbon-carbon double bonds, carbonyl groups or nitriles) in close proximity to the carbon radical interact and give rise to abnormal products. Details will be discussed in the following sections. 

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