Reaction chemoselective

A chemoselective reaction is a reaction in which a reagent reacts with one functional group in preference to another. For example, because sodium borohydride caimot reduce an ester, an amide, or a carboxylic acid, it can be used to selectively reduce an aldehyde or a ketone in a compound that also contains a less reactive carbonyl group. Water, not aqueous acid, is used in toe second step of toe reaction to avoid hydrolyzing toe ester. 

Sodium (or lithium) in liquid ammonia can reduce a carbon-carbon triple bond, but not a carbon-carbon double bond. This reagent is therefore useful for reducing a triple bond in a compound that also contains a double bond. 

Reducing reagents that that are hydride ion donors, such as sodium borohydride, cannot reduce carbon-carbon double bonds or carbon-carbon triple bonds, because both toe hydride ion and toe double or triple bond are nucleophiles. Therefore, a carbonyl group in a compound that also has an alkene functional group can be selectively reduced. Water, not aqueous acid, is used in toe second step of toe reachon to avoid addition of toe acid to the double bond. 

What reducing agents should be used to obtain the desired target molecules  

Explain why carbon-nitrogen double bonds and carbon-nitrogen triple bonds can be reduced by hydride donors such as NaBH4, while carbon-carbon double bonds and carbon-caibon triple bonds cannot. 

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Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

The other approach uses the monoalkylation of qulnol (9) as the chemoselective reaction. The rest of the sequence is more advanced but the principle should be obvious,... 

An intramolecular cycloaddition also occurred with 3-ylidenepiperazine-2,5-diones such as 124 or 125, obtained by Wittig-Horner-Emmons reaction from phosphonate 121 and aldehydes 122 or 123, respectively. The products of the Diels-Alder reaction are the bridged bicyclo[2.2.2]diazaoctane rings 126 and 127 that have been found in biologically active secondary metabolite such as VM55599 and brevianamide A. The different type of structures employed in this case requires a chemoselective reaction in order to produce the expected products as single diastereoisomers after 20 days (Scheme 18) <2001JOC3984>. 

In the solid-state photoreaction of 24c, a more chemoselective reaction occurred and only p-thiolactam 25c was obtained almost quantitatively. Of particular importance is the finding that the solid-state photoreaction of 24c involves a crystal-to-crystal nature where the optically active p-thiolactam 25c is formed in specific yield. Furthermore, the X-ray crystallographic analysis revealed that the crystals of 24c are chiral, and the space group is P2j. Irradiation of crystals at 0 °C exclusively gave optically active P-thiolactam 25c, in 81% yield at 100% conversion (entry 5). As expected, the thiolactam 25c showed optical activity (81% ee). This reaction exhibited good enantioselectivity throughout the whole reaction, where a small difference was observed in the ee value from 97 to 81% ee with increasing conversion from 20 to 100% (entries 5 and 6). The solid-state photoreaction also proceeded without phase separation even after 100% reaction conversion. The crystal-to-crystal nature of the transformation was confirmed by X-ray diffraction spectroscopy. 

Bennasar et al. reported a new radical-based route for the synthesis of calothrixin B (378) (869). This synthesis starts from the 2,3-disubstituted N-Boc indole 1558 and uses a regioselective intramolecular acylation of a quinoline ring as the key step for the construction of the calothrixin pentacyclic framework. Chemoselective reaction of in s/fM-generated 3-lithio-2-bromoquinoline [from 2-bromoquinoline 1559 with LDA] with the 3-formylindole 1558 followed by triethylsilane reduction of the... 

Most of the examples given here involve fairly strong acid catalysts to effect fragmentations. Many ozonides are stable to mild acids, so that if a molecule contains other functionality, chemoselective reactions are possible. Reactions of compounds containing both an aldehyde and ozonide group (88) have been studied. The aldehyde could be protected as an acetal using ethylene glycol with... 

Trost s examples of chemoselective reactions include compounds displaying several functional groups either of the same type or of different types. Reactions of the former have already been described under the term site selectivity. 

PJ. Garegg, Some aspects of regio-, stereo and chemoselective reactions in carbohydrate chemistry, PnreAppL Cheat. 56 845 (1984) and references therein. 

What follows is an exceptionally chemoselective reaction for construction of the bromohydrin functionality. 

An A -methyl-amino-oxy amino acid has also been incorporated into peptides using standard SPPS procedures. Reaction of these peptides with native reducing sugars yields neoglycopeptides via a chemoselective reaction with the amino-oxy side chains, maintaining the linked sugars in their cyclic conformations and... 

As another alternative to triflates, aryl nonaflates (ONf) are easily prepared from phenol and commerically available perfluorobutane sulfonyl fluoride 243, and used for Pd-catalysed coupling with halides [111]. Aryl nonaflates are more reactive than aryl triflates. / -Iodophcnyl nonaflate (244) gives 245 by chemoselective reaction of the... 

Allylic phosphates are more reactive than allylic acetates. Chemoselective reaction of the allylic phosphate moiety of the bis-allylic compound 88 with one equivalent of malonate, without attacking the allylic acetate moiety, takes place to give 89. Then the aminated product 90 was obtained by the addition of amine [52],... 

HSAB is particularly useful for assessing the reactivity of ambident nucleophiles or electrophiles, and numerous examples of chemoselective reactions given throughout this book can be explained with the HSAB principle. Hard electrophiles, for example alkyl triflates, alkyl sulfates, trialkyloxonium salts, electron-poor car-benes, or the intermediate alkoxyphosphonium salts formed from alcohols during the Mitsunobu reaction, tend to alkylate ambident nucleophiles at the hardest atom. Amides, enolates, or phenolates, for example, will often be alkylated at oxygen by hard electrophiles whereas softer electrophiles, such as alkyl iodides or electron-poor alkenes, will preferentially attack amides at nitrogen and enolates at carbon. 

Smith s synthesis of (—)-echinosporin stands out for its good stereo-and regiocontrol at every stage. Its large number of highly chemoselective reactions, and its use of an asymmetric [2 + 2]-photocycloaddition reaction for constructing the m-fused 6,5-bicyclic core are also commendable. The latter reaction provides a beautiful illustration of how properly harnessed photochemistry can be decisively deployed for the stereocontrolled synthesis of complex natural products. 

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