Nosyl protecting group

Again, sulfoxide imination is stereospecific and free NH-sulfoximines such as 9 may be obtained with retention of stereochemistry by cleavage of the nosyl protecting group (Scheme 2.1.1.5) [23]. 

Based on the aforementioned examples, it is the facile removal of the nosyl protecting group developed by Fukuyama that makes this methodology useful. Treatment of a nosyl protected amine with a variety of thiols, or other nucleophiles, gives the Meisenheimer complex 12. Upon loss of SO2, this generates the desired secondary amine 5 along with a thioether 13a-c which must be removed. 

The Fukuyama amine synthesis has seen wide application in the context of natural product synthesis. Complex polyamine natural products that highlight the orthogonal nature of the nosyl protecting group, such as lipogrammistin-A12 and various spider toxins,13 have been efficiently synthesized. This protocol has also been used in the context of medicinal chemistry,14 glucosylamines,15 and blasticidin amino acids.16... 

Ethynyl aziridine 1199 and tyrosine derivative 1200 were coimected to 1201 by ring opening of the aziridine in 90% yield. After removal of the nosyl protecting group, the resulting firee amine was subsequently coupled with A-Cbz valine (for... 

Example 19 Crich and Dudkin have used phosphoroamidite containing two different protecting groups 0-benzyl-0-2-cyanoethyl-iV,Ar-diisopropyl-phosphoroamidite [48]. This phosphitylating reagent was prepared in excellent yield from 2-cyanoethyl NyN diisopropylchlorophosphoroamidite, which was immediately used for coupling with an appropriate alcohol in the presence of tetrazole and oxidized without delay with TBHP. This kind of phosphorylation procedure was used in the synthesis of 4,8,12,16,20-pen-tamethyl-pentacosylphosphoryl / -o-mannopyranoside, an unusual / -man-nosyl phosphoisoprenoid from Mycobacterium avium. 

The nosylate has become a popular protective group because of the mild conditions for its cleavage. Its primary liability is in the fact that the nitro group is relatively easy to reduce, which should be remembered in planning a complex synthesis. The nitrobenezenesulfonamide is stable to strong acid and strong base. 

The method was quite efficient when several imine substrates with different protective groups were screened, with the nosyl derivatives (p-nitrophenylsulfonyl groups) being the best substrates. In the case of chelating bi-phosphane ligands (such as 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP)), the arylation was very slow, showing remarkable preference for mono-phosphane... 

After protection, the a-hydroxy esters can be reduced by DIBAL-H into O-protected a-hydroxyaldehydes that are very useful synthetic intermediates (e.g., leukotrienes,7-9 ionophore antibiotics,10 insect pheremones,11 etc.). The secondary hydroxyl group of the a-hydroxy esters may also be substituted with inversion of configuration after activation as triflates of nosylates (p-nitrobenzenesulfonates) to give a-alkyl esters12 ora-amino esters.13... 

Secondary hydroxyl groups also react if sufficient amount of rm-butylchlorodi-phenylsilane — imidazole — DMF reagent is used. The less hindered OH-2 of 1,4-anhydro-5,6-0-isopropylidene-D-glucitol was silylated in more than 78% yield [447]. Of the two secondary hydroxyl groups of the 4, 6 -0-isopropylidene-a-D-glucopyra-nosyl part of a kinetic acetonation product of maltose, that one at C-3 was selectively protected [448]. 

The next phase of the synthesis involved the transposition of aldol adduct 61 to the protected "aldol" adduct 60. (3-Hydroxyketone 61 was subjected to conditions (NaBH4, AcOH) which effected a direct reduction of the carbonyl moiety of 61 and thereby introduced the axial C(9) hydroxyl functionality of 67 with complete stereocontrol through an intramolecular delivery of hydride within an alkoxide intermediate at C(7). After diprotection of both hydroxyl groups of 67, chemoselective deprotection of hydroxyl at C(7) and Swern oxidation, ketone 60 was isolated. The enolate derivative of 60 could be stereoselectively p-methoxybenzylated, and the resulting ketone was reduced to the wrong equatorial alcohol 68. The C(7) stereogenic center was inverted by treatment of the nosylate derivative of 68 with rubidium acetate to afford the desired acetate 69 accompanied by the syn elimination product (15%). 

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