Chiral dioxane acetals reaction

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... 

Under a nitrogen atmosphere, a hexane solution of butyllithium (650 pL, 1.00 nunol) was added to bromobenzene (157 mg, 1.00 mmol) in Et20 (0.5 itiL) at 0 X. The mixture was stirred at room temperature for 1 h and then cooled to -78 °C. Trimethoxyborane (104 mg, 1.00 mmol) was added to the reaction mixture. The mixture was stirred at -78 C for 30 min and then at room temperature for 1 h. To the mixture were added H2O (18 mg, 1.00 mmol), isopropyl tra s-2-hexenoate (262) (62 mg, 0.40 mmol), and a solution of Rh(acacXC2H4)2 (3.1 mg, 12 pmol) and (S)-BINAP (9.0 mg, 14 pmol) in dioxane (2.0 mL). The whole mixture was heated at 100 C for 3 h. Addition of saturated aqueous sodium bicarbonate followed by ethyl acetate extraction and chromatography on silica gel (hexane ethyl acetate = 10 1) gave 90 mg (96% yield) of isopropyl 3-phenylhexanoate 264 as a colorless oil. HPLC analysis was performed on a Shimadzu LC-9A (Shimadzu Corp. Nakagyo-ku, Kyoto, Japan) and a JASCO PU- 980, with a JASCO UV-970 UV detector (Jasco Inc., Easton, MD, U.S.A), liquid chromatographic system with chiral stationary phase columns Chiralcel OD-H, OJ and OG, (95% ee). ... 

Asym. synthesis. A stirred soln. of startg. optically pure dioxane (prepared from (S)-( + )-butane-l,3-diol) and 4 eqs. of ethyl bromozinc-acetate (prepared from ethyl bromoacetate and Zn-Cu couple) in methylene chloride at —78° treated with 3 eqs. TiCl4, and quenched with 10% NaHC03 when reaction complete ca. 1 h) - product. Y 82% (diastereomer ratio 3.0 1). F.e. with racemic acetals s. T. Basile et al., J. Chem. Soc. Chem. Commun. 1989, 596-7 chiral a-alkoxynitriles with Me3SiCN/TiCl4 s. A. Solladie-Cavallo et al.. Tetrahedron Letters 29, 2955-8 (1988). 

Chiral dioxanones have also been employed as acetal auxiliaries in nucleophilic additions [33, 34]. Because of the inherent differences between carbox-ylates and alcoholates as leaving groups, it is the carboxylate that exclusively undergoes displacement. This was shown for the chiral l,3-dioxan-4-one 49 in its reaction with trimethylsilyl acetylene to give 50 in 99 1 dr (Equation 3)... 

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