2.6- Dialkoxy ketones

Diastereoselective reduction of acyclic a, -dialkoxy ketones.3 Reduction of the ketone 2 with this hydride results in the alcohol 3 with high syn-selectivity (97 3). The same syn-selectivity is observed with lithium trisiamylborohydride, but the yield is lower. The product was used for a synthesis of (+ )-4, a pheromone of a species of ants. 

Silyl enolates of a,a-dialkoxy ketones react with furans to form [3 4- 4] cycloaddition products in the presence of SbCls (Eq. 6) [17], Cycloaddition also occurs when 2,2-dialkoxycyclopropanecarboxylic esters and carbonyl compounds are treated with SbCls [18]. 

Several of the stabilized ylide reactions with ketones also follow consistent patterns. Thus, a-hydroxy ketones afford ( )-enoates (Table 20, entries 5, 21, 22,44) (144), while most of the a-alkoxy derivatives favor the (Z)-isomers (entries 70, 74) (164). There is at least one exception in the a-alkoxy series where the ( )-enoate is favored (entry 77) (165), and there are several cases of puzzling selectivity with a,a -dialkoxy ketone substrates (entries 71,72,74) (164). As in many of the ketone Wittig entries, the observations are interesting and high selectivity is often possible. However, the results appear specific to a given class of substrates, and there are insufficient data to establish general trends. 

The hypothesis of the A -thiazolium-2-ylide intermediate (10) as a key intermediate is consistent with the fact that electrophilic aldehydes can promote the addition of 2-TST (1) to electrophilic ketones, in particular to a.a -dialkoxy ketones. The effect of several aldehydes on the rate of the reaction of 2-TST (1) with two different ketones (13 and 14), at different temperatures and at different concentrations of the ketones and aldehydes, was studied. It was found that electron-poor aldehydes, particularly 2-fluorobenzaldehyde, enhance the rate of addition of 2-TST (1) to those studied ketones (eqs 21 and 22). 

Amino-Alditols.- Anti-selective reduction of acyclic or-alkoxy and of, -dialkoxy ketone oximes occurs with aluminium hydride reagents, L-threo-ketotetrose derivatives (24) giving L-xylitol... 

Acetals and Acylals. Acetals, which contain the group >C(OR)2, where R may be different, are named (1) as dialkoxy compounds or (2) by the name of the corresponding aldehyde or ketone followed by the name of the hydrocarbon radical(s) followed by the word acetal. For example, CH3—CH(0CH3)2 is named either (1) 1,1-dimethoxyethane or (2) acetaldehyde dimethyl acetal. 

The titaniated (25)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazines derived from cyclo(L-Val, Gly) or cyclo(L-Val, Ala) (1, R1 = H, CH3) react with a,/I-unsaturatcd aldehydes exclusively by 1.2-addition (cf. nearly exclusive 1,4-addition of ,//-unsaturated ketones with cuprate complexes of 2,5-dialkoxy-3,6-dihydropyrazines, see Section D. 1.5.2.3.1.4.) in a highly diastereoselective mode to give virtually only the (l S,2R)-diastereoniers 2 ". In reactions with the corresponding lithiated pyrazines both regioselectivity and diastereofacial differentiation at C-2 are also remarkably high (dc 95 %), but the diastereomeric excess at C-l is substantially smaller (30 50%) ... 

The use of alkyl esters in place of ketones resulted in the formation of alkoxypyrimidines 33 which could be converted in high yields, via selective sequential nucleophilic substitutions, into amino dialkoxy and trialkoxy pyrimidines 34 <06EJO3332>. 

The alkylation of metalated imines, hydrazones, 4,5-dihydrooxazoles, 4,5-dihydroisoxazoles, 5,6-dihydro-4/7-1,2-oxazines and 2,5-dialkoxy-3,6-dihydropyrazines (i.e., azaenolates) is a commonly used method in asymmetric synthesis of enantiomerically enriched aldehydes, ketones, spiroacetals, amines, /J-oxo esters, carboxylic acids, lactones, 1,3-amino alcohols, /(-hydroxy ketones and amino acids. 

The Addition of Alcohols to Aldehydes and Ketones Dialkoxy-de-oxo-bisubstitution... 

In the presence of base, alcohols and phenols add l,5-diphenylpenta-l,4-diyn-3-one (72JOU1398). At 40 °C addition occurs at both triple bonds to give a mixture of the 1,5-dialkoxy compound (411), the triketone and the pyran-4-one. On treatment with acid the former compounds are converted into the pyranone. However, at 15 °C only one triple bond is attacked giving the alkoxyvinyl ethynyl ketone (412), but this also forms the pyranone with acid (Scheme 136). 

The reaetion of ketones (with the exception of methyl ethyl ketone) with 1 and diiso-propy lethyl amine (DPEA) leads to regioselective formation of alkcny loxy dialkoxy boranes. A methyl group is deprotonated with high selectivity. A group is deprotonated almost exclusively in the presence of a CHR, group to form the (Z)-enolate (equation 1). ... 

All the members of this class of compounds contain an aromatic ketone group, the most representative systems being benzoin [71], benzoin ethers [72], dialkoxy-acetophenones [73], hydroxyalkylphenones [74], benzoyloxime esters [75] and, more recently, benzoylphosphine oxides [76], a-hydroxymethylbenzoin sulfonic esters [77], sulfonyl ketones [78] and morpholino ketones [70],... 

Extension of the scope of the methodology to a full stereocontrol in the addition sequence A in order to obtain either, Z-anti- or l,2-ry -diol units was hampered by the inherent //-selectivity of the addition of 2-TST to a,/3-dialkoxy aldehydes. Control of the selectivity by the use of Lewis acids acting as chelating agents was also foiled by substantial decomposition of 2-TST. This limitation was overcome by conversion of the 7 //-adduct into the syn-isomer via an oxidation-reduction sequence <1989JOC702>. The secondary (Rj-alcohol 457 was oxidized to ketone 461 with potassium permanganate partly solubilized with TDA-1 (tris[2-(2-methoxyethoxy)ethyl]amine). It was proved that under these neutral nonaqueous oxidation conditions no appreciable racemization occurred via exchange... 

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