De-ferf-butylation

The use of Nafion-H in de-ferf-butylation—in fact, trans-fcrf-butylation—has been extensively studied by Olah, Yamato, and co-workers. An early study established275 that ferf-butyl-substituted aromatics, when treated in the presence of a suitable acceptor compound, are easily de-ferf-butylated over Nafion-H used in catalytic amount [Eq. (5.106)]. Additional compounds including substituted biphenyls, bibenzyls, and cyclophanes, along with a range of substituted ferf-butylphenols, all gave de-ferf-butylated products in high (80-97%) yields. 

Figure 5.33 presents Friedel-Crafts acylations, taking benzoylations of toluene (top line) and para-tert-butyl toluene (Figure 5.33, bottom) as an example. The methyl group of toluene preferentially directs the benzoyl residue into the para-position. The ortho-benzoylated toluene occurs only as a by-product. In para-tert-butyl toluene both the methyl- and the tert-butyl substituent direct the electrophile towards the ortho-position, since both para-positions are occupied and could at best react with de-ferf-butylation, i.e., in a—sterically hindered — ipso-substitution (cf. Figure 5.5). Indeed, we see reaction ortho to the methyl group and not ortho to the ferf-butyl group. This selectivity can be ascribed to minimized steric interactions in the preferred sigma complex intermediate.

Fig. 5.4. De-ferf-butylation/re-ferf-butylation as a possibility for isomerizing tert-butylated aromatic compounds via Ar-SE reactions.

Reaction sequences similar to those portrayed in Scheme 7 should also be applicable to the other calixarenes obtained by de-ferf-butylation of 67 (n = 5, 6, 7, 8), as depicted in Scheme 8. Some of these transformations have already been demonstrated 12S), while others remain to be investigated. De-terf-butylation of />-/err-butylcalix[6]-arene (67, n = 6) and p-/< rt-butylcalix[8]arene (67, n = 8) proceed fairly smoothly to afford the corresponding calix[6]arene (68, n = 6) and calix[8]arene (68, n = 8). Conversion of 68 (n = 6) to the hexa-allyl ether (69b, n = 6) followed by Claisen rearrangement produces a modest yield of p-allylcalix[6]arene (70, n = 6). Similar reactions have been shown to take place in the calix[8]arene series as well125), although the yields are much lower and the products have not yet been fully characterized. 

The only way to functionalize the upper rim of 4-f-butylcalix[4]arene is to remove the f-butyl group and replace it with something more useful. Two methods have been reported by which this de-ferf-butylation, sometimes referred to by the more evocative term of neutering , may be achieved. The first method is probably the more conventional of the two and involves the use of aluminium trichloride and phenol. It is in essence a Friedel-Crafts reaction where a f-butyl group is attached to either benzene or phenol the innovation is that the source of the f-butyl substituent comes from the calixarene [1]. This retro-Friedel-Crafts reaction is thus an effective method for transalkylation that removes an unwanted alkyl group from calix[4]arenes as shown in Figures 3.10 and 3.11. Moreover, it is possible to subtly alter the reaction conditions and partially de-ferf-butylate... 

De-ferf-butylation of p-ferf-butylcalix[4]arene with Nation a new route to the synthesis of completely and partially debutylated p-ferf-butylcalix[4]arenes, S. G. Rha and S.-K. Chang, J. Org. Chem., 1998, 63, 2357. 

Bartl, P. and Korte, F. Photochemisches und thermisches verhalten des herbizids sencor (4-amino-6-ferf-butyl-3-(methylthio)-l,2,4-triazin-5(4/ -on) als festkorper und orf oberflachen, Chemosphere, 4(3) 173-176, 1975. 

Other chiral azomethine ylide precursors such as 2-(ferf-butyl)-3-imidazolidin-4-one have been tested as chiral controllers in 1,3-dipolar cycloadditions (89). 2-(ferf-Butyl)-3-imidazolidin-4-one reacted with various aldehydes to produce azomethine ylides, which then were subjected to reaction with a series of different electron-deficient alkenes to give the 1,3-dipolar cycloaddition products in moderate diastereoselectivity of up to 60% de. 

Even ferf-butylbenzene reacts satisfactorily (86% yield) without de-tert-butylation. Acylation of p-xylene with benzoic acid gave 71% yield with continuous removal of water. Water removal was also the decisive factor in producing anthraquinones with phthalic anhydride in satisfactory yields (52-89%). 

Reaction of 9-fluoro-7-oxo-2,3-dihydro7H-pyrido[l,2,3-de][l,4]oxa-zine-6-carboxylate and ferf-butyl (2-mercaptoethyl)carbamate in DMSO at 100 °C for 5 h gave 9-[2-(ferc-butoxycarbonylamino)ethylthio] derivative (06WOP2006/050943). The iodo atom of 9-iodo-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylic acids was coupled with 4 -0-(2-allyloxyethyl)azithromicin in MeCONMe2 in the presence of Bu3N and fra s-di-g-acetato-bis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) and di(ferf-butyl)-4-methylphenol at 110-115 °C for 15-17 h to give a mixture of 9-(3-substituted prop-1- and -2-enyl) derivatives (07WOP2007/ 054296). 10-methoxy and 10-cyano-3-hydroxymethyl-2,3-dihydro-5H-pyr-ido[l,2,3-de][l,4]benzoxazin-5-ones were obtained from 10-bromo derivative by reaction with NaOMe in the presence of Cu(I)I at 140 °C in DMF,... 

This same situation occurred in the de-fert-butylation of Figure 5.3 mono- and not di-ferf-butyl benzene was produced because the reaction was carried out in benzene. 

Huige and Hezemans179 180 have performed extensive molecular mechanics calculations using the consistent force-field method on various oligo- and polyisocyanides. The hexadecamer of ferf-butyl isocyanide was calculated to have a helical middle section and disordered ends. The dihedral angle N=C—C=N in the middle section was found to be 78.6°, and the number of repeat units per helical turn was 3.75. The latter number is in agreement with circular dichroism calculations using Tinoco s exciton theory (3.6—4.6) and De Voe s polarizability theory (3.81). The molecular mechanics calculations further predicted that the less bulky polymers 56 and 57 form helical polymers as well, whereas a disordered structure was calculated for poly(methyl isocyanide) (55). 

Ein Zusatz von Schwermetall-Salzen zur Bindung des freigesetzten Thiols eriibrigt sich bei der saurekatalysierten Spaltung von ferf.-Butyl-(3-hydroxy-l-alkenyl)-sulfanen165 z.B. ... 

Oxidation of thiophene dioxides 6 with ra-CPBA in the presence of sodium carbonate proceeds rather slowly, but affords the corresponding epoxides, 179 and 180, generally in good yields (Scheme 100) [217, 245, 246]. The oxidation takes place more quickly with highly congested substrates such as 3,4-di-ferf-butyl-2,5-dimethyl- and 3,4-di(l-adamantyl)-2,5-dimethylthiophene 1,1-dioxi-des (Table 11). This is probably due to the activation of the double bonds by ste-ric hindrance (destabilization of HOMO) and also relief of steric crowding for the epoxide formation. 

The polymerization of co-ester monomers with metallocene catalysts has been investigated by Aaltonen. Hakala, and co-workers. Methyl 9-de-cenoate and ferf-butyl 10-decenoate are copolymerized with propylene using Et(Ind)2ZrCl2 or ethylene using (n-BuCp)2ZrCl2 (4000 equiv MAO, 30 °C, 2.5—3 bar olefin, toluene solvent, preaddition of MAO to the ester monomer). In all cases, loss of catalyst activity was seen, although the ferf-butyl ester caused less catalyst deactivation than the methyl ester. The resultant propylene copolymers are well-defined (A/w ss 30 000, PDI 1.8-1.9, 133-139 °C) and the... 

As an example, ferf-butyl (45)-l-methyl-2-oxoimidazolidine-4-carboxylate was used by Nunami and colleagues as a chiral auxiliary for DKR of a-bromo-carboxylic acids. In this case, the nucleophile was a malonic ester enolate and the role of the polarity of the solvent (hexamethylphosphoramide, HMPA) was demonstrated (Scheme 1.2). The alkylated products were further easily converted to chiral a-alkylsuccinic acid derivatives and chiral jS-amino acid derivatives. Moreover, these authors showed that this methodology could be extended to other nucleophiles such as amines." Therefore, the reaction of a diastereomeric mixture of tert-bvAy (45)-l-methyl-2-oxoimidazolidine-4-carb-oxylate with potassium phthalimide predominantly afforded fcrf-butyl (45)-1-methyl-3-((25)-2-(phthaloylamino)propionyl)-2-oxoimidazolidine-4-carboxylate in 90% yield and 94% diastereomeric excess (de). The successive removal of the chiral auxiliary afforded A-phthaloyl-L-alanine. 

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