Chiral dioxane acetals

Denmark SE, Almstead NG (1991) Stereoselective opening of chiral dioxane acetals. Nucleophile dependence J Org Chem 55 6485-6487... 

Denmark studied fhe reactivity and stereoselectivity of group 14 allylic organo-metaUic compounds toward chiral dioxane acetals [16]. Allylation with allyltributylstannane was significantly more selective than that with allyltrimethylsilane for several chiral dioxane acetals examined (Tab. 11.1). 

Allylation of dioxane acetals (cf. 12, 375-378). Allylation of chiral dioxane acetals such as 2 has been shown to proceed with marked stereoselectivity with al-lyltrimethylsilanc promoted by TiCl4/Ti(0-i -Pr)4. A more recent study, indicates that... 

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... 

In asymmetric Strecker synthesis ( + )-(45,55 )-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has been introduced as an alternative chiral auxiliary47. The compound is readily accessible from (lS,25)-2-amino-l-phcnyl-l,3-propancdioI, an intermediate in the industrial production of chloramphenicol, by acctalization with acetone. This chiral amine reacts smoothly with methyl ketones of the arylalkyl47 or alkyl series48 and sodium cyanide, after addition of acetic acid, to afford a-methyl-a-amino nitriles in high yield and in diastereomerically pure form. 

Harwood and co-workers (105) utihzed a phenyloxazine-3-one as a chiral derived template for cycloaddition (Scheme 4.50). An oxazinone template can be formed from phenylglycinol as the template precursor. The diazoamide needed for cycloaddition was generated by addition of diazomalonyl chloride, trimethyl-dioxane-4-one, or succinimidyl diazoacetate, providing the ester, acetyl, or hydrogen R group of the diazoamide 198. After addition of rhodium acetate, A-methylmaleimide was used as the dipolarophile to provide a product that predominantly adds from the less hindered a-face of the template in an endo fashion. The cycloaddition also provided some of the adduct that approaches from the p-face as well. p-Face addition also occurred with complete exo-selectivity. Mono- and disubstituted acetylenic compounds were added as well, providing similar cycloadducts. 

Substituted 5-methylene-l,3-dk>xepines 38 are converted into vinyl acetals 39 by Ni catalysts bearing (R,R)-DuPHOS or (R,R)-ChiraPHOS as chiral ligands (Scheme 11) [16]. Similarly high enantioselectivity can be achieved with 5-methyl-ene-l,3-dioxanes as substrates [17]. Chiral Ru-catalysts are less efficient [18]. Cyclic acetals obtained are an useful starting material for preparation of macrolide antibiotics and other polyketide-derived natural products. 

To a stirred solution of a,/ -unsaturated aldehyde (0.5 mmol) in dioxane (7 mL) at 13 °C was added catalyst (20.4 mg, 0.05 mmol, 10 mol%) and, after a further 5 min, crystalline dihydropyridine (Hantzsch ester, 129.2 mg, 0.51 mmol). After a reaction time of 48 h the mixture was poured into distilled water (20 mL) and extracted with DCM (2 x 125 mL). The combined organic layers were dried (MgSCh), filtered, and concentrated. The product was isolated by FC (Si02, ethyl acetate/hexane) to give the saturated aldehyde. Enantiomeric excess was measured by chiral stationary phase GC-analysis. 

Acetals as Chiral Auxiliaries. There have been many applications of acetals of 2,4-pentanediol as chiral auxiliaries to control the diastereoselectivity of reactions on another functional group. Examples include cyclopropanation of alkenyl dioxanes, lithium amide-mediated isomerization of epoxides to allylic alcohols, and addition of dioxane-substituted Grignard reagents or organolithiums to aldehydes. 

A similar approach to enantiomericaUy pure norbornene derivatives was developed by Nouguier et al. who employed l,3 2,4-di-0-methylene acetals of pentitols as chiral templates [62]. Hence, the 5-(5-acryloyl-D-arabinatol derivative 82 underwent highly stereoselective Lewis acid catalyzed cycloaddition with cyclopentadiene, giving 83 (Scheme 10.28). The stereochemical outcome of the reaction was explained in terms of the chelate complex 84, in which the chair-like dioxane ring and the acrylic moiety are fixed in two parallel planes, forcing the diene to approach the cisoid acrylate from the ii-face. The synthesis and utihty of various methylene protected glycosides have also been reported by this group [63-66]. 

Acetals prepared from chiral diols and carbonyl compounds serve as a chiral synthetic equivalent of aldehydes or ketones. 1,3-Dioxanes synthesized from chiral 2,4-pentanediols are especially useful, and high asymmetric inductions are observed in the Lewis acid promoted reactions of a variety of organometallic compounds. After the removal of the chiral auxiliary by the oxidation and -elimination procedures, optically active alcohols are obtained. Optically active propargylic alcohols and cyanohydrins are synthesized from organosilane compounds, TMS-C CR or TMS-CN in the presence of TiCU (Scheme 24). 1 6-138 Reactive wganometals such as alkyl-lithiums, -magnesiums or -coppers also react with chiral... 

Cleavage of chiral acetals. ( 4/ ,6/ )-4,6-Dimethyl-l,3-dioxanes undergo reductive ring opening to give mainly the product with (5)- configuration at the newly formed stereogenic center. 

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