1.3- Dioxan-5-ones, aldol

Aldol Addition of 2-terf-Butyl-6-methyl-l,3-dioxan-4-one to Propanal Single Procedure117 ... 

For the formation of unexpected aldols by reaction of (25.6R)-2-rt rr-butyl-6-trifluoromcthyl-1,3-dioxan-4-one with 2-methylpropanal, 2.2-dimethylpropanal, and cyclohexanecarboxaldc-hyde, see J.-M. I.apierre, M. Gautschi, G. Grei-veldingcr, D. Seebach, Chem. Ber. 126,2739(1993). 

The boron enolates derived from (5)-4-silylated 2,2-dimethyl-l,3-dioxan-5-one undergo anti diastereoselective aldol reactions which provide access to protected oxopolyols of high stereochemical integrity <96SYN1095>. 

The focus in this section is the electrophilic a-functionalization of 2,2-dimethyl-l,3-dioxan-5-one. Various reactions have been carried out, such as alkylations, aldol additions, Mannich reactions, and transition metal-catalyzed reactions. Conditions were described for diastereoselective transformations, or auxiliary controlled diastereoselective transformations, providing enantiomerically pure products, and enantioselectively catalyzed reactions using organo-catalysts. 

The cyclizations of the adducts from 2-bromothiophenol and various (it)-5-ylidene-l,3-dioxan-4-ones lead exclusively to (+)-(rR,2R,3R)-3-(l-hydroxyethyl)-2-methylthiochroman-4-ones through opening of the dioxanone ring and loss of Me3G-CHO. However, the adducts from the (Z)-isomer also lose the hydroxyethyl unit, presumably as MeCHO by a retro-aldol reaction, and yield (—)-(2T)-2-methylthiochroman-4-ones. The structures of the supposed enolate intermediates arising from the initial loss of pivaldehyde have been MM2-optimized and show that steric repulsion between the R1 and methyl group in the enolate from the latter isomer is sufficient to promote the retro-aldol reaction (Equations 17 and 18) <2001EJ0529>. 

Table 2.4 (S)-Proline-catalyzed aldol reactions of 2,2-dim iethyl-1,3-dioxan-5- one [18]. ...

The use of protected dihydroxyacetone (eg. 25) improves considerably the stereochemical outcome of the reaction. In this regard, Barbas 111 and co-workers [140] have reported the organocatalyzed aldol reaction of dihydroxyacetone variants such as l,3-dioxan-5-one and... 

Die deprotonation and alkylation of 2-r-butyl-6-methyl-l,3-dioxan-4-ones has been accomplished, in a piece of work related to the aldol reactions of deprotonated 2-t-butyl-6-methyl-... 

Development of Anti-Selective Glycolate Aldol Methodology Based on the 2,3-Diaryl t,4-Dioxan-5-one Template 47... 

A prior derivatization of glycolic acid into chiral 5,6-diphenyl-l,4-dioxan-2-one paves the way to anfi-2,3-dihydroxycarboxylic acids by an aldol-type process. ... 

The precursor to amidoacrolein 64, 1,3-dioxin 66, was prepared as follows [39] the imine derived from the condensation of 2,2-dimethyl-l,3-dioxan-5-one with aminoacetaldehyde dimethyl acetal was acetylated with acetic anhydride/triethylamine to afford dioxin 66 in 83% yield (Scheme 24). Retro Diels-Alder of dioxin 66 in warm benzonitrile (120 C, 16 h) generated the amidoacrolein 64, which was trapped in situ with the silyloxydiene 65 to afford the desired cycloadduct 63 (64%). An aldol cyclization between the acetamide and neighboring aldehyde functionalities within 63 proceeded smoothly (2 equiv. of KCh-Bu, 10 equiv. of EtOAc, THF, 0 °C, 40 min) and directly afforded the corresponding conjugated lactam. This product was of sufficient purity for the second aldol reaction, which was best accomplished under acidic conditions, presumably proceeding through the achiral keto aldehyde intermediate 62 enroute to the desired, but racemic, (3-hydroxy ketone 61 obtained in 79% yield after the two consecutive ring closures. 

Synthesis of (4R,5S,6S,4 S)-2-(2,2-dimethyl-l,3-dioxan-4-yl)-5-hydroxy-2,4,6-tri-methyl-lO-undecen-3-one 16 A solution of ethyl ketone 15 (1.17 g, 5.45 mmol) in THF (1.0 mL) was added to a freshly prepared solution of LDA [nBuLi (3.34 mL, 1.6 m solution in hexanes, 5.35 mmol, 0.98 equiv) was added to a solution of diisopropylamine (749 pL, 5.35 mmol) in THF (4.0 mL) at 0 °C] dropwise at —78 °C. The solution was stirred for 1 h at —78 °C. Aldehyde 7 (688 mg, 5.45 mmol, 1.0 equiv) was added dropwise and stirring was continued for 45 min at —78 °C. The reaction mixture was quenched by dropwise addition of saturated aqueous NH4CI solution at —78 °C. The organic layer was separated and the aqueous layer was extracted with Et20. The combined extracts were dried over MgS04 and concentrated in vacuo. Flash chromatography (pentane/Et20 = 10 1) of the residue afforded anti-Cram aldol product 16 (1.36 g, 73%) and Cram aldol product (57 mg, 3%) as colorless oils. 

---