From D-mannitol

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

A detailed spectroscopic and theoretical study of the conformation of dioxolanes 1 has appeared <96T8275>, and a theoretical study has shown that the anomeric effect explains the non-planarity of 1,3-dioxole <96JA9850>. The tetraalkynyldioxolanone 2 has been prepared and its structure and reactivity studied <96HCA634>. Both enantiomers of the chiral glycolic acid equivalent 3 can be prepared from D-mannitol <96HCA1696>, and lipase-mediated kinetic... 

The guanidino analogue 90 of the 7-membered cyclic urea system was prepared, enantiomerically pure, from D-mannitol. The derivative 90 selectively inhibits bovine kidney a-L-fucosidase at 2.8pM <00BMC307>. 

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. 

Scheme 24.3 The preparation of diastereomeric diols from D-mannitol.

Scheme 33.7 MannOP ligands synthesized from D-mannitol.

Montgomery and Wiggins47 have studied the reaction of D-mannitol with hydrochloric acid in detail and the results throw some light on the mode of formation of isomannide from D-mannitol. When D-mannitol is heated under reflux with hydrochloric acid for several days, isomannide results in about 35-40% yield. But when D-mannitol is heated under pressure with fuming hydrochloric acid l,6-dichloro-l,6-didesoxy-D-mannitol (40% yield) and very little isomannide are formed. On examination of the residues after separation of isomannide from the first reaction mentioned above, no fewer than two monoanhydrohexitol derivatives and three new dianhydrohexitol derivatives were encountered. The products isolated are summarized in Table II. 

This procedure describes the preparation and use of an effective chiral catalyst for the asymmetric allylation of aldehydes. A previous synthesis of optically pure 1-(phenylmethoxy)-4-penten 2-ol requires seven steps from D-mannitol.4 This procedure has been employed successfully with other aldehydes,5 and also with methallyltributylstannane5 (see Table). Catalysts prepared from (R)- or (S)-BINOL and Ti(0-i-Pr)4 at 2 1 stoichiometry have also proven useful in these reactions.The olefinic products may be regarded as latent aldol products between aldehydes and the enolate of actetaldehyde or acetone. In all cases examined thus far, enantioselectivity... 

Carbohydrates remain an attractive source of chirality in preparation of ligands for asymmetric catalysis. Functionalized phospholanes, 192 [167], and chiral bisphosphinites 193 [168] with an attached crown ether unit were obtained recently from D-mannitol and from phenyl 2,3-di-0-allyl-4,6-0-benzylidene-p-D-glucopyranoside, respectively (Figure 18). Compounds 194 and 195 were obtained in the photochemical addition of H2P(CH2)3PPH2 onto the crresponding alkenes - Pd-complexes of these new bisphosphines were successfully applied as catalysts in the copolymerization of CO and... 

Figure 14. Chiral 1,2-diols that have been incorporated into monocyclic crown compounds. Listed under (o) are piecursors with C2 symmetry obtained from L-taitaric acid and L-thieitol, as well as from (5S)-hydrobenzoin as its p-methoxy analog, under (b) are precursors with Cj symmetiy obtained from D-mannitol and L-iditol, and under (c) are asymmetric precursors obtained from (5)-lactic acid, (5)-mandelic acid, and L-glyceraldehyde dithioethylacetal.

M. Fuzier, Y. Le Merrer, and J.-C. Depezay, Thiosugars from D-mannitol, Tetrahedron Lett., 36 (1995)6443-6446. 

An alternative synthesis of lactone derivatives (178) from (D)-( + )-mannitol was also reported, c.f. ... 

McQuade et al. [11] have pubhshed a nice synthesis using a microencapsulated nickel-based catalyst for promoting a Henry reaction based upon the work of Evans [12]. Torrens et al. have pubhshed a somewhat longer synthesis from D-mannitol bisacetonide [13]. 

O-isopropylidene-D-glycerol 22 (easily obtained from D-mannitol) as the starting material. After protection of OH-3, the acetal is removed to afford a... 

A similar approach was used by Mihailovic and coworkers.16 When 2-te-trahydrofuranethanol (119) was treated with lead tetraacetate, an intramolecular ring-closure occurred, to give a 45% yield of (R, flJ-m-2,6-dioxabicy-clo[3.3.0]octane (115), together with seven other compounds in minor proportions. Compound 115 was prepared from D-mannitol by following the established procedure of Cope and Shen,193 and was used as an intermediate for the first synthesis of thiacyclodeca-4,7-diene.200 Finally, several... 

Optically active (S)-benzyl 2,3-epoxypropyl ether can be obtained in quantity in seven steps from D-mannitol according to literature procedures.4 7... 

Treatment of tetrahydrothiepine 1,1-dioxide 99 derived from D-mannitol with KOH/CCI4 at 25 °C for 2h gave cyclohexene 100 in 94% yield (Scheme 12), which was converted by acid treatment to the enantiopure (-)-conduritol E derivative 101 <1997TL7797, 1999PS305>. 

Many other variations of the basic structure 10 have been explored, including an-hydro sugars and carbocyclic analogs, the latter derived from quinic acid 13 [23-26]. In summary, the preparation of these materials (e.g. 14-16) requires more synthetic effort than the fructose-derived ketone 10. Occasionally, e.g. when using 14, catalyst loadings can be reduced to 5% relative to the substrate olefin, and epoxide yields and selectivity remain comparable with those obtained by use of the fructose-derived ketone 10. Alternative ex-chiral pool ketone catalysts were reported by Adam et al. The ketones 17 and 18 are derived from D-mannitol and tartaric acid, respectively [27]. Enantiomeric excesses up to 81% were achieved in the epox-idation of l,2-(E)-disubstituted and trisubstituted olefins. 

Three-step synthesis starting from D-mannitol... 

Ph Ph Epoxidation of aldehydes [6.8] Three-step synthesis starting from D-mannitol... 

---