Secondary alcohols fluoride

It was obviously of interest to determine whether other esters of fluoroacetic acid would prove to be more or less toxic than the methyl ester. In the phosphorofluoridate series, for example, we found that esters of secondary alcohols were far more potent than those of primary alcohols for instance, di-isopropyl fluorophosphonate (I) was a compound of considerable activity. Accordingly ethyl, ra-propyl and isopropyl fluoroacetates were prepared by heating the corresponding esters of chloroacetic acid in the rotating autoclave with potassium fluoride. The toxicity figures of these esters were very similar to those of methyl fluoroacetate. 

The carbomagnesiation also takes place with S-substituted vinylsilane 96, which represents a more difficult class of substrate (Scheme 65) °. The three-component assembled product 97 is converted to the corresponding secondary alcohol 98 by fluoride-mediated oxidative cleavage of the carbon-sihcon bond (Scheme 65). 

Preparation of Tertiary and Secondary-Alkyl Fluorides from Alcohols with Hydrogen Fluoride-Pyridine Reagent... 

Fluorodehydroxylations of secondary and tertiary alcohols can be carried out very favorably at — 70 C up to + 50 C (0.5-3 h), when 70% hydrogen fluoride/pyridine (Table 17) or 86% hydrogen fluoride/melamine are used instead of anhydrous hydrogen fluoride itself.11 -31 -ii.266 Secondary alcohols react with 50- 70 % hydrogen fluoride/pyridine, frequently at room temperature. 

Carboxylates are stable to anhydrous hydrogen fluoride,30 but as described above, how ever, hemiacetal esters are readily cleaved and fluorinated by anhydrous hydrogen fluoride or 70% hydrogen fluoride/pyridine, this method has been widely applied in the synthesis of glycosyl fluorides from glycosyl esters for reviews see refs 29, 34, 277-279. 288, 289. Furthermore, p-toluene- or methanesulfonates (but not trifluoroacetates) of primary alcohols arc fluorinated by nucleophilic substitution using tctrabutylammonium hydrogen fluoride. This procedure is less suitable for secondary alcohols because of the considerable number of elimination products 306 for example, formation of 1 compared to 2.306... 

Disulfides are also formed in reactions of alkenes or secondary alcohols with the sulfur tetrafluoride/hydrogen fluoride/disulfur dichloride system under mild conditions. At elevated... 

The amino acids alanine and threonine have been treated40 with uranium(VI) fluoride both form gels from which alanine can be recovered unchanged while threonine is converted into 1-aminoacetone via oxidation of the secondary alcohol (> CHOH) moiety to a carbonyl group (> C = 0). 

This procedure describes an example of the "aldehyde route". The addition of 2-(trimethylsilyl)thiazole (2-TST) to aldehydes occurs readily and does not require the presence of a fluoride ion source.10 The resulting secondary alcohol is as a rule isolated in very good yield. The sense of the diastereofacial selectivity of the addition reaction to chiral a-amino aldehydes can be controlled by differential protection of the... 

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Recently Pagenkopf and Carreira reported that the addition of trimethyl aluminum to aldehydes can be catalyzed by the putative difluorotitanium-TADDOLate 29, giving secondary alcohols 30 of moderate enantiomerical purity (Scheme 4) [14]. In accordance with structural studies by Roesky, Noltemeyer, and co-workers [15] a fluoride bridging titanium and aluminum is postulated for the transition state. 

NT0-Bis(terf-butyldimethylsilyl)acetaniide silylates tertiary and hindered secondary alcohols in the presence of a catalytic amount of TBAF or another source of fluoride anion [Scheme 4.67].113 Protection of primary hydroxyl groups in the presence of secondary ones and secondary in the presence of tertiary is possible but the monoprotection of 1,2-diols fails due to the migration of the silyl group caused by the presence of basic fluoride anion. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

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