Diols acetals

Other possibilities are four-step sequences comprising full protection of the acetal diols, followed by removal of the acetal and, finally, regioselective protection of the obtained diol (Scheme 3.25). For example, 2,6-protection (acetylation, benzoylation or benzylation) of a 3,4-0-isopropylidene derivative and successive acetal cleavage yields the 3,4-diol. Subsequent 3-0-protection via tin-activated silylation, alkylation or acylation, or 4-O-protection via orthoester or benzylidene (endo) formation-opening sequences is then possible. 

Applications of chirally modified titanium Lewis acids have been reported most cases use various acetal diols derived from tartrate as the chiral auxiliary26 33,31 90. Various methods of catalyst preparation are known, as well as the use of different types of dienes (open-chained, cyclopentadiene) and dienophiles (acroleins, acrylates, crotonates, fumarates and amides derived from oxazolidinone), including intramolecular cycloaddition30. Addition of 4 A molecular sieves can improve asymmetric induction31,34 (as observed with the Sharpless epoxidation, loc. cit 31 in ref 6) and shows remarkable solvent effects on enantioselectivity. This method has been applied to the asymmetric Diels-Alder cycloaddition of cyclopentadiene and open-chain dienes to acrylamides28, 35. 

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). 

The syntheses of brevicomin (67)[109,110] and frontalin[l 11] have been achieved as an elegant application of the intramolecular acetal formation with the diol 66 in dry DME. Optically active frontalin (68) has been synthesized by this cyclization in triglymejl 12]. 

Efficient acetalization of alkenes bearing various EWG with an optically active 1.3-diol 72 proceeds smoothly utilizing PdCN, CuCI. and O2 in DME to give the 1,3-dioxane 73[113], Methacrylamide bearing 4-t-butyloxazolidin-2-one 74 as a chiral auxiliary reacts with MeOH in the presence of PdCE catalyst... 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

The reaction of a halide with 2-butene-1,4-diol (104) affords the aldehyde 105, which is converted into the 4-substituted 2-hydroxytetrahydrofuran 106, and oxidized to the 3-aryl-7-butyrolactone 107[94], Asymmetric arylation of the cyclic acetal 108 with phenyl triflate[95] using Pd-BINAP afforded 109, which was converted into the 3-phenyllactone 110 in 72% ee[96]. Addition of a molecular sieve (MS3A) shows a favorable effect on this arylation. The reaction of the 3-siloxycyclopentene 111 with an alkenyl iodide affords the. silyl... 

Diols that bear two hydroxyl groups m a 1 2 or 1 3 relationship to each other yield cyclic acetals on reaction with either aldehydes or ketones The five membered cyclic acetals derived from ethylene glycol (12 ethanediol) are the most commonly encoun tered examples Often the position of equilibrium is made more favorable by removing the water formed m the reaction by azeotropic distillation with benzene or toluene... 

Reaction is acid catalyzed Equilibrium constant normally favorable for aide hydes unfavorable for ketones Cyclic acetals from vicinal diols form readily... 

Acetals are readily formed with alcohols and cycHc acetals with 1,2 and 1,3-diols (19). Furfural reacts with poly(vinyl alcohol) under acid catalysis to effect acetalization of the hydroxyl groups (20,21). Reaction with acetic anhydride under appropriate conditions gives the acylal, furfuryUdene diacetate... 

I60C-Hydroxy Derivatives of Gorticoids and their Acetonides. The preparation of 16a-hydroxy-9a-fluoroprednisolone (48) from the 3,20-bisethylene ketal of hydrocortisone acetate (49) has been reported (73). The latter was dehydrated with thionyl chloride in pyridine to yield the 4,9(11),16-triene (50). The 16,17-unsaturated linkage was selectively hydroxylated with OsO /pyridine to yield the 16a,17a-diol (51), which was converted... 

An early attempt to hydroformylate butenediol using a cobalt carbonyl catalyst gave tetrahydro-2-furanmethanol (95), presumably by aHybc rearrangement to 3-butene-l,2-diol before hydroformylation. Later, hydroformylation of butenediol diacetate with a rhodium complex as catalyst gave the acetate of 3-formyl-3-buten-l-ol (96). Hydrogenation in such a system gave 2-methyl-1,4-butanediol (97). 

Heating with cuprous chloride in aqueous hydrochloric acid isomerizes 2-butene-l,4-diol to 3-butene-l,2-diol (98)] Various hydrogen-transfer catalysts isomerize it to 4-hydroxybutyraldehyde [25714-71-0] (99), acetals of which are found as impurities in commercial butanediol and... 

Acetals andKetals. Acetals of 1,3-diols are prepared by refluxing the diol with the aldehyde in the presence of an acid catalyst, even in an aqueous medium. The corresponding ketals are more difficult to prepare in aqueous solution, but cycHc ketals of neopentyl glycol, eg, 2-butyl-2-ethyl-5,5-dimethyl-l,3-dioxane (3), can be prepared if the water of reaction is removed azeotropicaHy (34). 

Polyesters. Polyesters containing carbonate groups have been prepared from this diol (see Polycarbonates) (99). Films of this polymer, formed from an acetone or ethyl acetate solution, exhibit exceUent adhesive properties. 

Cyclic ether and acetal polymerizations are also important commercially. Polymerization of tetrahydrofuran is used to produce polyether diol, and polyoxymethylene, an excellent engineering plastic, is obtained by the ring-opening polymerization of trioxane with a small amount of cycHc ether or acetal comonomer to prevent depolymerization (see Acetal resins Polyethers, tetrahydrofuran). 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Lipase-catalyzed enantioselective transesterification of 0-substituted-l,2-diols is another practical route for the synthesis of P-blockers. Lipase PS suspended in toluene catalyzes the transesterification of (63) with vinyl acetate to give the (5)-ester in 43% yield and >98% ee (78). The desired product, optically pure (R)-ttitylglycidol, is then easily obtained by treating the ester with alcohoHc alkaU. Moreover, Pseudomonas Hpase catalyzes the acylation of oxazohdinone (64) with acetic anhydride in very good yield and selectivity (74). PPL-catalyzed transesterification of a number of /n j -norbomene derivatives proceeds in about 30% yield and 92% ee (79,80). 

CH2=C(OBn)(CH3), POCI3 or TsOH, 61-98% yield. It should be noted that these conditions do not afford a cyclic acetal with a 1,3-diol. This ketal is stable to LiAlH4, diisobutylaluminum hydride, NaOH, alkyllithiums, and Grignard reagents. 

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