Chiral dithianes

While zeolites are themselves rarely chiral, adsorption of chiral inductors can enable enantioselective or diastereoselective reactions. For instance, Y zeolites have been modified with chiral dithiane oxides (47) Ramamurthy and his group have... 

Dithiane 1-oxide derivatives as chiral auxiliaries and asymmetric building blocks for organic synthesis 980PP145. 

In one case, the addition of lithiated 1,3-dithiane to ( )-l-nitropropene gave an adduct in modest enantiomeric excess (43% ee). In an independent study chiral lithium [(S)-(l-(dimethylamino)-ethyl](methyl)phenylcupratc and lithium mcthoxy(methyl)eupratc were reacted with ( )-(2-ni-troethenyl)benzene to give adducts in 1-2% enantiomeric excess36. 

The addition of a lithiated dithiane to a chiral a,/J-unsaturated sulfone has been reported, however, the stereochemical outcome and the diastereoselectivity was not addressed20. The addition of (lithiomcthylsulfonyl)benzenc to a chiral y-alkoxy-a-trimethylsilyl-aj-unsaturated sulfone gave exclusively the, vr -adduct1 2 3 4 5 7 8 9 10 11 12. 

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... 

ABSTRACT Zeolite Y modified with chiral sulfoxides has been foimd catal rtically to dehydrate racemic butan-2-ol enantioselectively depending on the chiral modifier used. Zeolite Y modified with R-l,3-dithiane-1-oxide shows a higher selectivity towards conversion of S-butan-2-ol and the zeolite modified with S-2-phenyl-3-dithiane-1-oxide reacts preferentially with R-butan-2-ol. Zeolite Y modified with dithiane oxide demonstrates a significantly higher catalsdic activity when compared to the unmodified zeolite. Computational simulations are described and a model for the catalytic site is discussed. 

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... 

Whereas the mono- and the S/S-dithioether moieties have been used to date, the 1,3-dithianyl motif was used for the first time in 2005 by Ricci et al. as a new hybrid ligand in asymmetric catalysis. Hence, a series of new chiral oxazoline-1,3-dithianes have been successfully applied to the copper-catalysed conjugate addition of ZnEt2 to enones (Scheme 2.16). The expected products were obtained in almost quantitative yields and enantioselectivities of up to 69% ee. 

Scheme 2.16 Cu-catalysed 1,4-additions of ZnEt2 to enones with chiral oxazoline-1,3-dithiane ligands.

Carbolithium compounds of moderate reactivity open the O—C bond of cyclic sulfate esters or cyclic sulfamidates to produce new C—C links, as shown, for example, in equation 112 for a chiral cyclic sulfamidinate and 2-lithio-l,3-dithiane (380a). More reactive organolithium species, such as n-BuLi and PhLi, yield mixtures of products, probably due to attack on the S atom of the sulfonamido group too °. 

Enantiopure 77 was easily prepared by treatment of 2-trimethylsilyl-l,3-dithiane 75 and chiral epoxides 76 in a sequential addition in the presence of a crown ether. In this sequence, a monosUylated 1,5-diol 77 is obtained, allowing a discrimination of the two... 

The enantioselective lithiation of anisolechromium tricarbonyl was used by Schmalz and Schellhaas in a route towards the natural product (+)-ptilocaulin . In situ hthi-ation and silylation of 410 with ent-h M gave ewf-411 in an optimized 91% ee (reaction carried ont at — 100°C over 10 min, see Scheme 169). A second, substrate-directed lithiation with BuLi alone, formation of the copper derivative and a quench with crotyl bromide gave 420. The planar chirality and reactivity of the chromium complex was then exploited in a nucleophilic addition of dithiane, which generated ptilocaulin precnrsor 421 (Scheme 172). The stereochemistry of componnd 421 has also been used to direct dearomatizing additions, yielding other classes of enones. ... 

In the desulfurization of 3,6-disubstituted-l,2-dithianes with chiral phosphines (Scheme 33) <2000J(P1)1595>, enantiomerically enriched tetrahydrothiophenes 134 with up to 36% ee were obtained. Both yield and ee proved to be dependent on solvent, temperature, and the phosphine employed. 

Optically active 2-alkylidene-l,3-dithiane 1,3-dioxides have been prepared as chiral Michael-type acceptors. It was shown that these compounds react under nucleophilic epoxidation conditions to give diastereoselectively the epoxides. Other heteroatom nucleophiles reacted as well <1998JOC7128, 1999PS(153/4)337>. It was further demonstrated that enolates were also effective nucleophiles for the stereoselective addition to 2-alkylidene-l,3-dithiane 1,3-dioxides (Scheme 48) <20050L4013>. 

The use of chiral 2-alkylidene-l,3-dithiane 1,3-dioxides in asymmetric cycloaddition reactions has been demonstrated. A highly enantioselective synthesis of (—)-cispentacin by an intramolecular 1,3-dipolar cycloaddition was reported (Scheme 52) <20020L1227, 20030BC684>. 

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>. 

The oxidation of prostereogcnic sulfides to yield chiral nonracemic sulfoxides, which was reported to proceed with good predictive power in the sense indicated (p401)14. As an application of this rule see the assignment of the absolute configuration 2-ethy]-2-(l-oxo-propyl)-l,3-dithiane 1-oxides (11 and 12, p409)103. 

The l,3-dithiane-l,3-dioxides can also be prepared by sodium periodate oxidation of the 1,3-dithiane, and the irons isomer was thus obtained in a 58% recrystallized yield [81]. Chiral molecules of this type (C2 symmetry ) are particularly suitable for use as chiral acyl anion equivalents [11,82]. 

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)). 

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