2-Alkoxy-1,3-diols

Diastereoselective hydroboration Hydroboration of a-alkoxy-/ , y-unsaturatcd esters with BHj S(CH1)2 (1.05 cquiv.) in THF at 0 — 20° followed by standard oxidation affords 2-alkoxy-1,3-diols with significant diastercoselectivity. 

Titanium chelates are formed from tetraalkyl titanates or haUdes and bi- or polydentate ligands. One of the functional groups is usually alcohoHc or enoHc hydroxyl, which interchanges with an alkoxy group, RO, on titanium to Hberate ROH. If the second function is hydroxyl or carboxyl, it may react similarly. Diols and polyols, a-hydroxycarboxyflc acids and oxaUc acid are all examples of this type. P-Keto esters, P-diketones, and alkanolamines are also excellent chelating ligands for titanium. 

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

The lithium 2-butenyl(triethyl)aluminate complex, prepared in situ from 2-butenyllithium and triethylaluminum, displayed poor diastereoselectivity in a reaction with benzaldehyde (anti/syn 56 44)7. (Z)-3-Alkoxy-substituted aluminate complexes such as A-C, however, give good diastereoselectivity in aldehyde addition reactions8. The reactions of A with aldehydes at —100 °C give the jyw-diol monoether with >95% diastereoselectivity and >80-95% regiose-... 

In the more successful reagents, the ligands have been selected in such a way that the metal center remains nonstereogenic, this has been achieved mainly by application of chiral diols with C2 symmetry or by introduction of two of the same alkoxy residues. 

Ceric ions react rapidly with 1,2-diols. There is evidence for chelation of cerium and these complexes are likely intermediates in radical generation10 106 The overall chemistry may be understood in terms of an intermediate alkoxy radical which undergoes p-scission to give a carbonyl compound and a hydroxyalkyl radical (Scheme 3.59). However, it is also possible that there is concerted electron transfer and bond-cleavage. There is little direct data on the chemical nature of the radical in termediates. 

Both the regiochemistry and stereochemistry of Wacker oxidation can be influenced by substituents that engage in chelation with Pd. Whereas a single y-alkoxy function leads to a mixture of aldehyde and ketone, more highly oxygenated systems such as the acetonide or carbonate of the diol 1 lead to dominant aldehyde formation.107 The diol itself gives only ketone, which perhaps indicates that steric factors are also important. 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

The Mn + complexed ions appear to be the most selective and efficient initiator system for grafting to polysaccharides so far described. The mechanism of the initiation reaction has been studied in our laboratories by model experiments and ESR spectroscopy. There are two possible reactions indicated. Bond cleavage of a vicinal diol according to reaction (22) is one possibility. Another and faster reaction with Mn3+ giving radicals appears to be oxidation of aldehyde groups (24) to alkoxy radicals ... 

More remarkably, the reaction forming the Mn-Pt species is unique among the compounds 144-149 in that three other metallacarborane products were also isolated from this system alone. These are two 12-vertex species, [l-Ph-2,2,2-(CO)3-7-X-8,8-dppe-/iyperc/oAo-8,2,l-PtMnCBgHg] pC = H (150), OEt (151)], and the complex [3,6,7- Mn(CO)3 -3,7-(p-H)2-l-Ph-6,6-dppe-c/oio-6,l-PtCBgH6] (152) formed by cluster contraction. Subsequent studies confirmed that the ethoxylated compound 151 is formed by reaction of 146 with adventitious EtOH present in the precursor 129. Indeed, treatment of 146 with other alcohols ROH afforded similar species [l-Ph-2,2,2-(CO)3-7-OR-8,8-dppe-/z3y crc/oA o-8,2,l-PtMnCBgHg] [R = Me (153), (CH2)20H (154), (CH2)40H (155)] with, surprisingly, only mono-cage products observed when diols were used as substrates. All of the alkoxy-substituted compounds 151 and 153-155 are relatively stable and do not react further, whereas... 

SCHEME 20. Debromination of bromoalkenes 146. Synthesis of diols 151, O-protected a-alkoxy aldehydes 152 and Q-.o- -dialkoxyketones 153 G = protecting group... 

To access anti-l,2-diols, indirect methods are required for the preparation of geometrically pure, chiral E-3-alkoxy reagents. To this end, the isomerization of alkenylboronic esters described above (Eq. 41), provides a reliable route to tartrate-derived E-3-siloxy allylboronate 99 (Fig. 7). The latter shows variable enantioselectivities in additions to aldehydes, with cyclohexanecarboxaldehyde affording the highest selectivity (Eq. 70). ... 

The oxygen atom has also been used to generate other functionalities, such as the aldehyde moiety in Kibayashi s syntheses of (—)-coniine (197) and its enantiomer (Scheme 1.43) (253). Here, reaction of tetrahydropyridine N-oxide 93 with a silylated chiral allyl ether dipolarophile 198 delivered the adduct 199 with the desired bridgehead stereochemistry via the inside alkoxy effect . Desilylation and hydrogenolytic N—O bond rupture with palladium(II) chloride provided the diol 200... 

Syntheses of simple diols are described first, followed by a multistep synthesis of ribose. These syntheses illustrate the compatibility of alkoxy substituents on boronic esters with their reaction with (dihalomethyl)lithium. The limitations of this compatibility, as well as failure of a (chloro-allyl)boronic ester to undergo substitution by alkoxides, are also noted. Retention of configuration of the migrating group is a consistent and repeated feature of these syntheses. 

In their quest for alkynyl-substituted 1,2-diols, Epsztein and workers examined additions of alkoxy allenylzinc reagents to aldehydes (Table 4)5. The reagents were prepared from various propargylic ethers by lithiation with BuLi followed by addition of Znl2. Although exact ratios were not determined, the major propargylic products were surmised to be the anti isomers based on spectral data and comparison with authentic samples. 

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