Diol derivatives

Thallium(III) acetate reacts with alkenes to give 1,2-diol derivatives (see p. 128) while thallium(III) nitrate leads mostly to rearranged carbonyl compounds via organothallium compounds (E.C. Taylor, 1970, 1976 R.J. Ouelette, 1973 W. Rotermund, 1975 R. Criegee, 1979). Very useful reactions in complex syntheses have been those with olefins and ketones (see p. 136) containing conjugated aromatic substituents, e.g. porphyrins (G. W. Kenner, 1973 K.M. Smith, 1975). 

Other minor raw materials are used for specific needs. Eumaric acid [110-17-8] the geometric isomer of maleic acid, is selected to maximize thermal or corrosion performance and is the sole acid esterified with bisphenol A diol derivatives to obtain optimum polymer performance. CycloaUphatics such as hydrogenated bisphenol A (HBPA) and cyclohexanedimethanol (CHDM) are used in selective formulations for electrical apphcations. TetrahydrophthaUc anhydride [85-43-8] (THPA) can be used to improve resiUence and impart useful air-drying properties to polyester resins intended for coating or lining apphcations. 

In addition, polyester polyols are made by the reaction of caprolactone with diols. Poly(caprolactone diols) are used in the manufacture of thermoplastic polyurethane elastomers with improved hydrolytic stabiHty (22). The hydrolytic stabiHty of the poly(caprolactone diol)-derived TPUs is comparable to TPUs based on the more expensive long-chain diol adipates (23). Polyether/polyester polyol hybrids are synthesized from low molecular weight polyester diols, which are extended with propylene oxide. 

A variety of cyclic ortho esters,including cyclic orthoformates, have been developed to protect czs-1,2-diols. Cyclic ortho esters are more readily cleaved by acidic hydrolysis (e.g., by a phosphate buffer, pH 4.5-7.5, or by 0.005-0.05 M HCl) than are acetonides. Careful hydrolysis or reduction can be used to prepare selectively monoprotected diol derivatives. 

The initial investigation focused on the use of threitol-derived auxiliaries with various substituent groups on the dioxolane ring (Table 3.3). However, it became evident that the oxygen atoms in the substituents had a detrimental effect on selectivity. Comparison of the diastereoselectivities for the ketals 69-71, which contain Lewis basic sites in the substituents at the 1 and 2 positions, with those from simpler diol derived ketals 72-74 demonstrates the conflicting effects of numerous coordination sites. The simpler, diol-derived ketals provide superior results compared to the threitol derived ketals. The highest diastereoselectivity is observed in the case of the 1,2-diphenyl ethane-1,2-diol derived ketal 74. 

As noted at the end of Section 7.8, the prefixes cis- and trans- would be ambiguous when naming the diols derived from 1-methylcyclohexene because the ring has three substituents. Instead, a reference substituent r is chosen and other substituents are either cis (c) or trans (f) to that reference. For the two l-methyl-l,2-cyc ohexanediol isomers, the -OH group at Cl is the reference (r-1), and the -OH at C2 is either cis (c-2) or trans (t-2) to that reference. Thus, the diol isomer derived by cis hydroxylation is named l-methyl-r-l,c-2-cyc ohexanediol, and the isomer derived by trans hydroxylation is named l-methyl-r-l,t-2-cyclohexanediol. 

Treatment of (5 )-4-benzyloxy-2-pentenyl(tributyl)stannane with tin(IV) chloride generates an intermediate which reacts with aldehydes to provide 1,5-diol derivatives with excellent stereoselectivity94. 

Alkoxyallylstannanes can be generated in situ by stannylation of allyl ethers or by 1,3-isomerization of isomers, and trapped by boron trifluoride-diethyl ether complex induced addition to aldehydes to give syn-diol derivatives 13,120. 3-Alkylthioallylstannanes can similarly be generated and trapped84. 

Table 7. Diols Derived from Various a,/f-Unsalurated Aldehydes 0...

The highest enantioselectivities in the base-catalyzed Michael additions have so far been obtained using achiral bases complexed to chiral crown ethers. The addition of methyl 2,3-dihydro-l-oxo-1//-indene-2-carboxylate (1) to 3-buten-2-one using 4 mol% of a [l,T-binaphthalcnc]-2,2 -diol derived optically active crown ether 3 in combination with potassium AY/-butoxide as the base illustrates this successful method 259 260 It is assumed that the actual Michael donor is the potassium enolate complex of 1 and crown ether 3. 

Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

Dendrons 21-23 are easily prepared on a multi-gram scale and are highly soluble in common organic solvents thanks to the presence of the four long alkyl chains per peripheral fullerene unit. Therefore, they appear to be good candidates for the preparation of fullerene-rich macromolecules, for example, as shown by their attachment to a phenanthroline diol derivative and the preparation of the corresponding copper(I) complexes (see below). 

In a few cases, the synthesis was directed towards well-defined oligomers (dimers, trimers, etc.). The synthesis of bis(5,7,3, 4 -tetra-0-benzyl)-EC 4/1,8-dimer from 5,7,3, 4 -tetra-0-benzyl-EC and 5,7,3, 4 -tetra-0-benzyl-4-(2-hydroxyethoxy)-EC was described by Kozikowski et al. [41]. This compound exhibited the ability to inhibit the growth of several breast cancer cell fines through the induction of cell cycle arrest in the Gq/Gi phase. Analogously, procyanidin-B3, a condensed catechin dimer, has been obtained through condensation of benzylated catechin with various 4-0-alkylated flavan-3,4-diol derivatives in the presence of a Lewis acid. This reaction led to protected procyanidin-B3 and its diastereomer. In particular, octa-O-benzylated procyanidin-B3 has been produced with high levels of stereoselectivity and in excellent isolation yields [42]. 

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

It was independently found by two groups that the exo-diol derived from bis(camphorsulfonyl)-substituted tra .s-cyclohexane-1,2-diamine ligand (HOCSAC) was an excellent promoter for the enantioselective addition of dialkyIzinc reagents to any type of ketones, even dialkyl ketones, in the presence of Ti(Oi-Pr)4. As shown in Scheme 4.11, excellent enantioselectivities of up to 99% ee were obtained in these conditions in combination with high yields and with a low catalyst loading of 2-10 mol%. 

Reductive elimination from 2-en-l,4-diol derivatives has been used to generate 1,3-dienes. Low-valent titanium generated from TiCl3-LiAlH4 can be used directly with the diols. This reaction has been used successfully to create extended polyene conjugation.305... 

The catalysis has been extended for use with chiral boronates and those from the phenyl-substituted bornane diol derivatives A and B54 have been found to be particularly effective.55... 

Fig. 11. Mechanism for formation of parabanic acids from the methylated uric acid-4,5-diol derived from theobromine (3,7-dimethylxanthine) and caffeine (1,3,7-trimethylxan-thine). Molar amounts of products are those formed in 1 M HOAc...

Fig. 11) would likely proceed by different mechanisms. Protonation of the diol (IV, Fig. 12) derived from theobromine would lead to ring opening at the C6— Cs position giving an imidazole isocyanate (XVI, Fig. 12). This could readily form XVII which after hydrolysis and loss of C02 would give dimethyl-allantoin (XVIII). On the other hand, the uric acid diol derived from caffeine (X, Fig. 12) cannot fragment by this mechanism. Accordingly, either or both of the processes could Occur via the form of the diol hydrated at the C6 carbonyl group (XIX, Fig. 12) which could readily lose C02 to give XX followed by rearrangement to trimethylallantoin (XXI).

Secondary rearrangement of the uric acid-4,5-diol derived from theobromine or caffeine to give a methylated alloxan is shown in IV - XXII and X XXIII, Fig. 13 respectively. 

Synthesis of Diethers and New Diols Derived from Dianhydrohexitols... 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

Attempted reaction of 1,3-pentadiene with the optically active diboron derived from dialkyl tartrate in the presence of a phosphine-free platinum catalyst gave poor diastereoselectivity (20% de).63 Better selectivity has been attained with a modified platinum catalyst bearing a PCy3 ligand (Scheme 6).64 The reaction of allylborane thus obtained with an aldehyde followed by oxidation with basic hydrogen peroxide affords the corresponding diol derivative with moderate ee. 

Zhou et al. have reported extensively on the use of a spiro-biindanediol as the backbone in the ligands 35a-f (Scheme 28.11, SIPHOS) [70]. Excellent results are obtained for a variety of substrates, and recently a full report has appeared on the use of these ligands [71]. Synthesis of the diol backbone requires a number of steps, including a resolution [72]. An additional and successful spiro-diol-derived phosphoramidite 39 has recently been disclosed by the group of Zhang [73]. 

In addition to ozonization, aqueous photolysis of metofluthrin (14) gave the diol derivative possibly formed through epoxidation of the prop-l-enyl side chain in the acid moiety followed by its hydrolysis [56]. 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

Polymer-supported [e.g. 8, 9] and silica-supported [10] cinchona alkaloids have been used in the asymmetric dihydroxylation of alkenes using osmium tetroxide. Enantiomeric excesses >90% have been achieved for diols derived from styrene derivatives. 

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