Unprotected 1,2-diols

The cyclic sulfites were first found to react with lithium phenoxides as nucleophiles in DMF in a one-pot procedure commencing from the unprotected diol [357]. Subsequent work opened up this class of donor to alcohol nucleophiles in conjunction with the use of a Lewis add, such as Yb(OTf)3 or Ho(OTf)3, to activate the donor in refluxing toluene (Scheme 4.57) [314,358,359]. The very high degree of P-selec-tivity observed in these reactions is consistent with an SN2-like displacement of the sulfite oxygen. 

Diols of different structures such as the meso-diol 76 (Fig. 41), the C2-symmetric diol rac-79 (Fig. 42), the diol rac-82 in which the primary hydroxy group is protected (Fig. 43) and the unprotected diol rac-84 with a primary and secondary hydroxy group (Fig. 44) were used as substrates in the lipase-catalyzed transesterification using vinyl acetate as acyl donor in organic solvents with the aim to prepare chiral buildings blocks of high enantiomeric purity.86... 

Model studies aimed at the synthesis of Calyculin discovered a subtle effect of a remote protecting group on the stereoselectivity of an epoxidation reaction [Scheme 1,46], 79 Treatment of the unprotected diol derivative 46.1 with potassium carbonate, benzonitrile and hydrogen peroxide gave a diastereoisomeric mixture of epoxides 46.2a,b (3 1) in favour of 46.2a. However, the same reaction performed on the terf-butyldiphenylsilyl ether 463 both increased the selectivity (1 18) and inverted its sense now 46 4b was the major product. 

To our mind, the enolate of 19 should exhibit a decided kinetic bias for kinetically controlled protonation on its a face because of the steric encumbrance associated with p proton delivery. In actual fact, rapid introduction of its lithium salt into a 1 4 mixture of water and tetrahydrofuran at -78 °C resulted in its quantitative conversion to 20 (Scheme III). Once the MOM groups had been removed, controlled oxidation with manganese dioxide led to 21, a very pivotal intermediate. To arrive at magellaninone (2), 21 was treated with methyllithium and the resulting unprotected diol 22 was directly reduced with lithium aluminum hydride. Subsequent Jones oxidation proceeded with the customary allylic rearrangement. 

In some cases where there is a neighboring group participation, aldehydes are formed from terminal olefins. The aldehyde 27 was obtained cleanly by participation of the cyclic carbonate of allylic diol 26, but the normal oxidation to afford the methyl ketone 29 occurred with the unprotected diol 28 [24]. 

Enantiopure alkenyl iodide 35 reacts with the unprotected diol 34 in the presence of palladium acetate to provide cyclopentanone 36 plus a diastereomer in 15% yield. 

Scheme 7 Generation of structurally diverse catalysts in situ enables screening and identification of a highly efficient and selective system for C-allylation of unprotected diol Ih...

Scheme 9 Catalyst-directed diastereo- and site-selectivity in the asymmetric /ert-(hydroxy)-prenylation of unprotected diol Ih...

Wang G, Franke J, Ngo CQ, Krische MJ (2015) Diastereo- and enantioseiective iridium catalyzed coupling of vinyl aziridines and alcohols site-selective modification of unprotected diols and synthesis of substituted piperidines. J Am Chem Soc 137 7915-7920... 

Section 2.5). In contrast, the unprotected diol 6.84 gave a mixture of products, including a bis-carbonylation product 6.86. The diol 6.84 could, however, be cyclized directly to diospongin A 6.83 by treatment with a stoichiometric amount of a palladium(II) complex and a phenyl tin reagent. Another synthesis of this natural product may be found in Scheme 8.93. 

Catalytic, enantioselective ring opening of meso epoxides with various alcohols and amines employing a combination of Sc(OTf)3 and 2,2 -bipyridine (3) (10 mol% each) was reported [130]. For both classes of nucleophiles, moderate to high yields and enantioselectivities were obtained with complete anti diastereoselectivity (Scheme 12.50). Aliphatic amines did not give the desired products, presumably due to catalyst inhibition. The PMB-protected diol was converted into the corresponding acyloin by oxidation with almost complete retention of configuration. Alternatively, oxidation with CAN furnished the unprotected diol. 

Bettucci L, Bianchini C, Oberhauser W, Hsiao T-H, Lee HM. Chemoselective aerohic oxidation of unprotected diols catalyzed by Pd-(NHC) (NHC=N-heterocyclic carbene) complexes. J Mo/ Catal A Chem. 2010 322 63-72. 

Finally, a very recent work described the synthesis of spacer-linked neodisaccharides of L-daunosamine [84], In a glycosylation reaction on a monosilylated 1,4-butanediol the main product obtained was the monoglycosylated unprotected diol. This may suggest either a desilylation due to the acidic conditions or a higher reactivity of the silylated oxygen of the acceptor. 

Selective reaction at the ci.s-2,3-diol grouping of unprotected D-ribonucleosides has occasionally been observed. Treatment of D-ribonucleosides with tris(tetramethylammonium) trimetaphosphate in M sodium hydroxide for 4 days at room temperature led to a mixture of nucleoside 2 - and 3 -phosphates in yields of >70% no 5 -phosphate was detected.213 Reaction of ethyl (trichloromethyl)phos-phonate with nucleosides in N,N-dimethylformamide containing triethylamine, followed by basic hydrolysis of the reaction product, yielded 2 (3 )-phosphates in variable yields.214 The participation of the cis-diol grouping in the reaction was suggested by the failure of thymidine or 2, 3 -0-isopropylideneuridine to undergo reaction. 

Abstract The telomerization of butadiene with alcohols is an elegant way to synthesize ethers with minimal environmental impact since this reaction is 100% atom efficient. Besides telomerization of butadiene with methanol and water that is industrially developed, the modification of polyols is still under development. Recently, a series of new substrates has been involved in this reaction, including diols, pure or crude glycerol, protected or unprotected monosaccharides, as well as polysaccharides. This opens up the formation of new products having specific physicochemical properties. We will describe recent advances in this field, focusing on the reaction of renewable products and more specifically on saccharides. The efficient catalytic systems as well as the optimized reaction conditions will be described and some physicochemical properties of the products will be reported. 

Likewise, unprotected polyhydroxy compounds can be successfully fluorinated to give the products resulting from substitution of the hydroxy groups by fluorine, wn-o-lnositol reacts with sulfur tetrafluoride and anhydrous hydrogen fluoride at ambient temperature to give a moderate yield of the cyclic sulfite ester of tw/o. cfo-5,6-difluoro-7-oxabicyclo[2.2.1 heptane-e.w,e.vo-2,3-diol (6) and, alter hydrolysis, the free difluoro diol 7.61... 

The complex of tartaric acid and antimony (emetic) was described three centuries ago. Nevertheless, the structure of this compound has been elucidated these last fifteen years by X-ray diffraction ( 1 ). In fact, emetic presents a binuclear cyclic structure. Many authors mentioned similar complex with transition metals (vanadium (2), chromium (3)) or metalloids (arsenic (4), bismuth (5)). Emetic with phosphorus was not mentioned. Nevertheless, tartaric acid or alkyl tartrates has been utilized in phosphorus chemistry tartaric acid reacts with trialkyl phosphites giving heterocyclic phosphites (6). Starting from alkyl tartrates, we prepared spirophosphoranes with a P-H bond and sixco-ordinated compounds (7). With unprotected tartaric acid, many possibilities appear condensation as a diol, as a di(oc-hydro-xyacid), or even as a 8-hydroxyacid. 

BDA protection of mannosides leaves the secondary 2-hydroxyl and the primary 6-hydroxyl unprotected. The tin-activated chloroacetylation of diol 100 gave the 6-chloroacetate 101 in excellent yield (Scheme 2.29) [147,183], Notably, benzylation... 

When reactions are performed on tributylstannyl ethers and dibutylstan-nylene acetals of hexopyranoside derivatives that have more oxygen atoms, including the primary one, unprotected, markedly different results are obtained, as shown in Figs. 24 and 25. Dibutylstannylene acetals favor reaction on the position in the 1,2-diol unit that is adjacent to an axial substituent, whereas tributyltin ethers prefer to react at the primary centers. However, this pattern was not observed for reactions of the tributylstannyl ether of l,2-(l-methoxyethylidene)-j3-D-mannopyranose, as shown in Fig. 26.122 Methylation of this compound through the tributylstannyl ether in toluene in the presence of added tetrabutylammonium bromide also gave substitution on 0-3 predominantly.123 These results may arise from distortion of the chair conformation by the fused isopropylidene acetal. 

The reactions of tributylstannyl ethers and dibutylstannylene acetals of diols or polyols containing one hydroxyl group that is at the end of a chain (terminal diols) are listed in Table IX. Some reactions on compounds of this type, primarily unprotected glycosides, have been discussed earlier, but for those examples, the terminal hydroxyl group was not critical in... 

As previously noted, dibutylstannylene acetals of all compounds that have a free primary hydroxyl group, including such compounds as methyl a-D-mannopyranoside or uridine, which have ds-l,2-diols unprotected, react with f-butylchlorodimethylsilane to give substitution on the primary oxygen atom in high yield.85 88 There is no evidence of any products of substitution on secondary oxygen atoms in these reactions. 

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