70% HF-pyridine

Benzyl carbamates are readily cleaved under strongly acidic conditions HBr, AcOH 50% CF3COOH (25°, 14 days, partially cleaved) - 70% HF, pyridine CF3S03H FSOaH, or CHjSO.H.- In cleaving benzyl carbamates from peptides, 0.5 M 4-(methylmercapto)phenol in CF3CO2H has been recommended to suppress Bn additions to aromatic amino acids. To achieve deprotection via an Sn2 mechanism that also reduces the problem of Bn addition, HF-Me2S-p-cresol (25 65 10, v/v) has been recommended for peptide deprotection. 

The completion of the total synthesis only requires a few deprotection steps. It was gratifying to find that the final deprotections could be conducted smoothly and without compromising the newly introduced and potentially labile trisulfide residue. In particular, exposure of intermediate 101 to the action of HF pyridine results in the cleavage of all five triethylsilyl ethers, providing 102 in 90% yield (Scheme 23). Finally, hydrolytic cleavage of the ethylene ketal with aqueous para-toluenesulfonic acid in THF, followed by removal of the FMOC protecting group with diethylamine furnishes calicheamicin y (1) (see Scheme 24). Synthetic calicheami-cin y, produced in this manner, exhibited physical and spectroscopic properties identical to those of an authentic sample. 

All that remains before the final destination is reached is the introduction of the C-l3 oxygen and attachment of the side chain. A simple oxidation of compound 4 with pyridinium chlorochro-mate (PCC) provides the desired A-ring enone in 75 % yield via a regioselective allylic oxidation. Sodium borohydride reduction of the latter compound then leads to the desired 13a-hydroxy compound 2 (83% yield). Sequential treatment of 2 with sodium bis(trimethylsilyl)amide and /(-lactam 3 according to the Ojima-Holton method36 provides taxol bis(triethylsilyl ether) (86 % yield, based on 89% conversion) from which taxol (1) can be liberated, in 80 % yield, by exposure to HF pyridine in THF at room temperature. Thus the total synthesis of (-)-taxol (1) was accomplished. 

Only two operations remain. Reaction of the enolic form of aldehyde 162 with Eschenmoser s reagent (H2C=NMe2+I-)62 in the presence of triethylamine provides the desired enal after a simple / -elimination. Finally, cleavage of the remaining tcrt-butyldi-methylsilyl ether with HF pyridine completes the total synthesis of (+)-brevetoxin B (1). 

In a related procedure, even benzene and substituted benzenes (e.g., PhMe, PhCl, xylenes) can be converted to phenols in good yields with sodium perborate F3CS020H. " Aromatic amines, N-acyl amines, and phenols were hydroxylated with H2O2 in SbFs—HF. Pyridine and quinoline were converted to their 2-acetoxy derivatives in high yields with acetyl hypofluorite AcOF at -75°C. ... 

In order to ameliorate the problem of solvolytic degradation, compound 109 was treated with TIPSOTf, to provide silyl ether 113 in 72% yield (Scheme 19). The acetonides were removed with PPTS in warm MeOH to provide a mixture of compounds in which the TBS groups were also partially removed. Exposure of this mixture to HF-pyridine successfully generated filipin III (114), in 39 % overall yield from 113. 

Nicolaou and coworkers reported a new method for preparing glyco-syl fluorides (38) from phenyl thioglycosides (37) by treatment with di-ethylaminosulfur trifluoride (DAST)-A -bromosuccinimide (NBS), or HF-pyridine-NBS, the phenylthio group of the thioglycosides being initially activated by NBS. Thus prepared were compounds 39, 40, and 42 (see Table I) and 3,4-C)-carbonyl-2,6-dideoxy-3-C-methyl-L-n Z)ohexo-pyranosyl, 2-azido-2,6-dideoxy-3,4-0-isopropylidene-D-altropyranosyl,... 

Scheme 4.14 Schreiber diversity-oriented synthesis plan (2000). (a) MeOH/THF, heat (57%) (b) 2KN(SiMe3)2, 2 CH2=CH2 Br (89%) (c) Grubbs catalyst (59%) (d) HF, pyridine (95%).

Oxazolidinones have also been used as intermediates in simple transformations utilising their peculiar reactivity. The absolute configuration of WBoc-P-aminoalcohol 213 can be easily inverted via Sn2 cyclisation to oxazolidinone 214 <00TL10071>. Treatment with Olah s reagent (HF-Pyridine) of 4-alkyl-5,5-diphenyl-oxazolidinones 216 afforded the corresponding a-(fluorodiphenylmethyl)alkylamines 217 <00TA2033>. 

Scheme 7-58. Reagents and conditions a PCC, NaOAc, benzene, reflux (64%). b (1) NaBH4, MeOH (79%) (2) HF pyridine, THF (85%).

Cyclization of mixed acetals (13,300).4 This reaction is a particularly useful route to eight-membered cyclic ethers (oxocanes) and provides the first practical route to a natural oxocene, (- )-laurenyne (3), from an optically active mixed acetal 1. Thus cyclization of 1 followed by O-desilylation affords 2 as the only cyclic product. Remaining steps to 3 involved C-desilylation, for which only HF/pyridine is useful, introduction of unsaturation into the C2-side chain, and extension of the C8-side chain. Exploratory studies showed that unsaturation at the p- or y-positions to the cite of cyclization of 1 prevent or retard cyclization with a wide variety of Lewis acids. The cyclization is apparently more tolerant of substitution in the terminator position, C3-Q, of the oxocene. 

Treatment of thioglycosides with /V-bromosuccinimide (NBS) in the presence of diethylaminosulfur trifluoride (DAST) or HF-pyridine complex furnishes glycosyl fluorides.23 These can be activated with AgC104/SnCL in the presence of another... 

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