Dithiane oxides alkylation

Diethyl-3,5-octadiene 174 Dithiane oxides alkylation of 84 carbanions of 84 Dithianes alkylation of 76,79 as acyl anion equivalents 75 carbanions of 76,79 cleavage of 14-18.76,79 desulfurization of 78 oxidation of 23... 

Variation of 2-alkyl substituent exerted an effect upon diastereoselectivity. The best diastereoselection was obtained when incorporating a 2-ethyl substituent for acyl dithiane oxides (Table 3.6). The diastereoselectivity and the sense of induced stereochemistry can be rationalized on the basis of a simple chelation control model. 

The cyclic a-lithio-l,3-dithiane S-oxide 406 was generated from compound 392 with n-BuLi at —10 °C and reacted with deuterium oxide, alkyl halides, carbonyl compounds and esters to afford the corresponding products 407 as mixture of diastereomers (Scheme 106)605 - 607. (V-Acyl imidazoles were better acylating agents than esters608. However, compound 406 has not been employed properly as acyl anion. Intermediate... 

I -oxo-1,3-dithian-2-y 1)- 1-alkanone 2-acyl- 13-dithiane 1-oxide (alkylation) 1455... 

In addition to the classical reactions, this book covers many techniques and reactions that have more recently gained wide use among practicing chemists. Molecular-orbital theory is introduced early and used to explain electronic effects in conjugated and aromatic systems, pericyclic reactions, and ultraviolet spectroscopy. Carbon-13 NMR spectroscopy is treated as the routine tool it has become in most research laboratories, and the DEPT technique is introduced in this edition. Many of the newer synthetic techniques are also included, such as asymmetric hydrogenation and epoxidation, use of sodium triacetoxyborohydride, Birch reduction, Swern oxidations, alkylation of 1,3-dithianes, and oxidations using pyridinium chlorochromate. 

Alkylation and acylation of dithiane oxides are highly stereoselective processes. In such transformations, it is noticed that the anti substrate leads to the syn acyldithiane oxide (Scheme 4.55), with the choice of base being pivotal in the process. The use of butyllithium for acylation and sodium t-butoxide/butyllithium mixtures for alkylation with aldehydes tends to give the cleanest and most efficient reactions. Of late, simple 2-substituted dithiane oxides have been prepared with very high enantioselectivity, and such compounds have become the preferred starting materials for the various systems under scrutiny. 

Carlson and Helquist410 were the first to perform the alkylation of 2-lithio 1,3-dithian-S-oxide 323 (equation 180). The yields of this reaction appeared, however, to be low. In spite of the fact that dithian-S-oxides have been intensively investigated268-411, their synthetic applications are rather limited. 

Cyclic dithioketals and acetals represent another important class of sulfur containing chiral auxiliaries, which are available in chiral form by biooxidation. Biotransformations were performed on a preparative scale using whole-cells (wild type and recombinant) and isolated enzyme. Again, enantiocomplementary oxidation of unsubstituted dithianes (linear and cyclic, R = H) was observed when using and CPMOcomo (Scheme 9.28) [211,212]. Oxygenation of functionalized substrates (R = substituted alkyl) with gave preferably trans... 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

The stereospecific base-cleavage of the trimethylsilyl group in 1,3-dithiane 1-oxides 499 enables to obtain the specifically deuteriated products 500 (equation 303), A nitro group in y-nitroalkyl sulphoxides 501 (obtained by the Michael addition of nitroalkanes to a, j8-unsaturated sulphoxides) is replaced by hydrogen by means of tributyltin hydride (equation 304). This reagent does not affect the sulphinyl function. The overall procedure provides an efficient method for the conjugate addition of alkyl groups to a, -unsaturated sulphoxides . ... 

Suda and coworkers described the anodic oxidation of 2-silyl-l,3-dithianes which have two sulfur atoms on the carbon adjacent to silicon [42], In this case, however, the C Si bond is not cleaved, but the C-S bonds are cleaved to give the corresponding acylsilanes (Scheme 12). Although the detailed mechanism has not been clarified as yet, the difference in the anode material seems to be responsible for the different pathway of the reaction. In fact, a platinum plate anode is used in this reaction, although a carbon anode is usually used for the oxidative cleavage of the C-Si bond. In the anodic oxidation of 2-silyl-l,3-dithianes the use of a carbon anode results in a significant decrease in the yield of acylsilanes. The effects of the nature of the solvent and the supporting electrolyte may also be important for the fate of the initially formed cation radical intermediate. Since various 2-alkyl-2-silyl-l,3-dithianes can be readily synthesized, this reaction provides a convenient route to acylsilanes. 

Oxidation of 1,3-dithianes to 1,3-dithiane 1-oxides has been carried out by various methods using H2O2 or /-butyl hydroperoxide (TBHP) as oxidant. In the presence of chiral co-oxidants, optically active 1,3-dithiane 1-oxides have been prepared (Scheme 66). A compilation of some currently used methods is given in Table 13. The oxidation to 1,3-dithiane 1,3-dioxides was conducted similarly. Sharpless conditions were found to be highly effective with 2-alkyl- or alkylidenyl-substituted substrates. The parent 1,3-dithiane 1,3-dioxide was obtained by basic removal of a 2-carboxyl group in 83% yield and 99% ee <1998JOC7306>. 

The chemistry of chiral 1,3-dithiane 1-oxides, in particular their use as chiral auxiliaries, has been reviewed <19980PP145>. Some further developments in this field are the stereoselective a-alkylation with alkyl halides <1997T13149> or a-hydrazination with di-fert-butyl azodicarboxylate (DBAD) <2000T9683>. The carbonyl group of 2-acyl-l,3-dithiane 1-oxides was also used as an electrophile (Scheme 82). Interestingly, acyclic enolates react with these substrates to give a 95 5 mixture of anti- and ry -adduct, whereas cyclic enolates produce a mixture of anti- and ry -adduct in 8 92 ratio <2000JOC6027>. 

From the synthetic point of view, the most important a-sulfinyl carbanions appear to be those derived from dithioacetal S-oxides which are a synthon for acyl anions65. However, the yields of the alkylation reaction were found to be low. In spite of the fact that dithiane S-oxides have been intensively studied66 63, their synthetic applications are limited,... 

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

Acyl silanes by anodic oxidation of2-alkyl-2-trialkylsilyl-l,3-dithianes... 

A Pummerer reaction may feature in the epimerisation of syn-2-acy 1-2-alkyl-1,3-dithiane 1-oxides by TFAA (95S73). 

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