In situ protection

Flame spray metallising is widely used for the protection of metal against corrosion, especially for in situ protection of stmctural members. The principal metal used for spraying of plastics is sine. Aluminum and copper are also used. If the distance from the part is too great, the zinc solidifies before it touches the part and adhesion is extremely poor. If the molten zinc oxidizes, conductivity and adhesion are poor. If the distance is too short, the zinc is too hot and the plastic warps or degrades. These coatings are not as dense as electrically deposited coatings because of numerous pores, oxide inclusions, and discontinuities where particles have incompletely coalesced. 

Silyl-derived protective groups are also used to mask the thiol function. A complete compilation is not given here since silyl derivatives are described in the section on alcohol protection. The formation and cleavage of silyl thioethers proceed analogously to simple alcohols. The Si—S bond is weaker than the Si—O bond, and therefore sulfur derivatives are more susceptible to hydrolysis. For the most part silyl ethers are rarely used to protect the thiol function because of their instability. Silyl ethers have been used for in situ protection of the — SH group during amide formation. ... 

Reaction of 2,4-(lH,3H)-quinazolinedione 250 for 8h at 130°C with two equivalents of N-2-hydroxyethylpiperazine 251 (the alcohol group of which is in-situ protected by silylation), HMDS 2, and catalytic amounts of TSOH H2O, and subsequent transsilylation with boiling methanol, affords 68% of the monoaminated product 252 and methoxytrimethylsilane 13 a. Reaction of 250 with fivefold excess of N-2-hydroxyethylpiperazine 251 in the presence of octamethylcyclotetrasilazane... 

Conjugate addition of vinyl-, aryl-, heteroarylcuprates 90 to the cyclobutenedione 63, followed by in situ protection with (methoxyethoxy) methyl chloride of the enolates, provides a method for synthesizing substituted catechol derivatives 91 [44], Regiocontrolled synthesis is achieved by using cyclobutenedione monoacetals 92 as starting substrates. (Scheme 32)... 

A-allylamine 23 (obtained by standard transformations of 6-iodogluco-side 22) underwent cyclization into the monocycle 24. However, when the amine was in situ protected as a Boc derivative it could be subjected to the RCM process. The products were further converted into the bicyclic aza sugar 26.19 A similar approach to eight-membered ring aza sugars was recently reported (Fig. 9).20... 

Termites and powder post beetles cause many thousands of dollars loss of wood installations. Creosoting and vacuum-pressure impregnation of Wolman salts into pine lumber provides protection however, there exist many structures where in situ protection against termites would be of value. 

The latter reaction could be repeated ten times without loss of activity of Yb-XN-1010. Similar results were obtained with ytterbium(III) loaded Amberlyst 15W resin in a two-step one-pot procedure first involving the formation of the active dimethyl acetal from a benzaldehyde derivative which was followed by in situ protection of sucrose (Scheme 4.17) [100]. 

Interestingly, indoles are lithiated at either the 2- or the 3-position, depending on protection at For 2-lithiation, probably the best technique is in situ protection of nitrogen... 

Hoye described an RCM-based total synthesis of the 20-membered marine macrolide dactylolide 288 and its subsequent conversion to the natural carbinolamide zampanolide 289 (Scheme 56), both feature a common highly unsaturated macrolide core, bridging a m-2,6-disubstituted 4-methylene tetrahydropyran unit. When the polyunsaturated acyclic lactone 286 (1 1 epimeric mixture around the /i r/-butyldimethylsilyl (TBS)-protected carbinol center) was in situ protected with bis-trimethylsilylacetamide (BSA) and then treated with catalyst G in benzene at 60 °C, each diastereomer smoothly cyclized to the corresponding cycloalkene 287 with exclusive ( )-geometry at the newly formed double bond. 

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

It is possible to oxidize alcohols in the presence of free carboxylic acids.206 Nevertheless, sometimes better results are obtained if the acid is protected, for example by methylation.207 Sometimes, free carboxylic acids have a low solubility in cold CH2C12. In such cases, an in situ protection with the silylating agent, bis(trimethylsilyl)acetamide (BSA) normally allows the solubilization of the acid as trimethylsilyl ester, and an easy Swern oxidation. The resulting silylated acid is easily deprotected during the work-up.208... 

The attack of OH at the methyl group of T was first followed by the release of 3H20 from DNA 3H-labeled at this position (Swinehart and Cerutti 1975). With aqueous solution and also within the phage an in situ protection factor of 9.4 was noticed, and for E. coli the corresponding value was 790. Interestingly, for the formation of the Tg lesion, the protection factors were noticeably lower, 1.3 and 140, respectively. In the phage, 200 of the latter lesions are formed at a dose equivalent to 37% survival as indicated by... 

The carbamates 459 (R = Or-Bu) behave similarly, though they must be lithiated with s-BuLi to avoid addition to the carbonyl group.418 It is possible simply to use a lithium carbamate to protect an amino group during a lateral lithiation an initial deprotonation and carbonation generates the lithium carbamate 466, which is then deprotonated twice more by r-BuLi. After electrophilic quench, acid hydrolysis of the carbamic acid returns the unprotected aniline.419 420 An alternative in situ protection sequence relies on temporary trimethylsilylation of the aniline.421... 

The benzannulation reaction further allows the concomitant generation of an axial and chiral plane in a single reaction step (Scheme 28) [68f]. The diastereomeric ratio of the benzannulation products depends on the protocol used for phenol protection. Thus, in situ protection gives the kinetic ratio of 74a 74b — 11 89, whereas a two-step benzannulation/ protection sequence results in thermodynamic control to give a ratio of 74a 74b >99 1. These results can be explained in terms of a possible or arrested rotation around the biaryl axis in the benzannulation product before protection to give either 74a or 74b. 

Ti(ISRi)i (1), Ti(NR,)4, R = CH, or C,H, is an excellent reagent for in situ protection of aldehydes and ketones by formation of adducts that revert to the original carbonyl compounds on aqueous work-up. Both la. R = CH, and lb, R = C,H, react more readily with aldehydes than with ketones, but la is more reactive in general than lb. Thus selective reactions can be conducted on a ketone group in the presence of an aldehyde group (equation I). The method can also be used to carry out selective reaction... 

The concept of in situ protection of the less hindered or more Lewis basic of two ketones to enable selective reduction of the usually less reactive groups has been successfully developed. The sterically hindered Lewis acid MAD (78) derived from BHT and trimethyl aluminum was used to coordinate preferentially to the less hindered ketone and DIBAL-H reduced the more hindered ketone that remained un-complexed. An approximate order of comparative reactivity for various classes of ketones has been established. The selectivity was improved by using the more hindered Lewis acid MAB (79) and/or di-bromoalane as the reducing agent. The discrimination between aromatic ketones is good but less successful between two dialkyl ketones. The chemoselectivity was demonstrated in the reduction of diketone (80) to keto alcohol (81) in 87% yield and excellent selectivity (equation 20). 

The tetrahedral intermediate generated by organometallic addition thus provides in situ protection of the ketone (equation 8). 

Some of the more common reagents for the conversion of carboxylic acids to trimethylsilyl esters are listed below. For additional methods that can be used to silylate acids, the section on alcohol protection should be consulted, since many of the methods presented there are also applicable to carboxylic acids. Trimethylsilyl esters are cleaved in aqueous solutions, and thus in. situ protection is preferred over direct isolation of the ester in most cases. 

More recently, the same catalyst was used to produce cyclic amines with retention of stereochemistry from a simple linear aliphatic azide [53]. Treatment of a substituted aliphatic azide by complex 66 afforded the cyclized compound 75, by insertion of the nitrene moiety in allylic, benzylic, and even in the less reactive tertiary C—H bonds. The catalyst is inhibited by coordination of the product to the metal center. However, that can be avoided by using an in situ protecting agent (Boep is preferred over Fmoc-OSuc which leads to catalyst decomposition). 

The standard solution for ketones and aldehydes is to nse protecting gronps snch as acetals, bnt this can be inconvenient or maybe incompatible with the prodnct dne to the conditions reqnired for deprotection. However, in situ protection as carbinolamine anions is an ideal solntion, being very efficient time-wise and process-wise." (Note that intermediates of the same type are formed dnring qnenching of lithio-compounds with DMF and can be used in the same way.)... 

Another, very nseful, in situ protection of indoles and pyrroles, involves deprotonation of the nitrogen then addition of carbon dioxide to give the lithinm iV-carboxylate salt." ... 

Lithiation of A-protected indoles is the main route to 2-boronic acids, which have found wide use, although the usual protecting groups (Boc and arylsulfonyl) increase the ease of deboronation. With Boc-protected derivatives, the indole is less consistent than the pyrrole in coupling reactions. In situ protection of the indole NH as the A-carboxylate can be used to prepare both the 2-boronic acid and 2-tri-n-butylstan-nane for one-pot coupling procedures. 

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