Chiral oxathianes

A 1,3-oxathiane chiral auxiliary derived from camphor has also been reported [58]. 

A. Mosandl and G. Heusinger. 1,3-Oxathianes, chiral fruit flavour compounds. 

Oxathiane 101 is readily deprotonated using s-BuLi, and the resulting anion reacts with alkyl halides, ketones, and benzonitrile (85JOC657). The majority of work in this area, however, is due to Eliel and coworkers and has involved chiral 1,3-oxathianes as asymmetric acyl anion equivalents. In the earliest work it was demonstrated that the oxathianes 102 and 103, obtained in enantiomeri-cally pure form by a sequence involving resolution, could be deprotonated with butyllithium and added to benzaldehyde. The products were formed with poor selectivity at the new stereocenter, however, and oxidation followed by addition... 

Solladie-Cavallo s group used Eliel s oxathiane 1 (derived from pulegone) in asymmetric epoxidation (Scheme 1.3) [1]. This sulfide was initially benzylated to form a single diastereomer of the sulfonium salt 2. Epoxidation was then carried out at low temperature with the aid of sodium hydride to furnish diaryl epoxides 3 with high enantioselectivities, and with recovery of the chiral sulfide 1. 

Solladie-Cavallo has recently reported a two-step asymmetric synthesis of dis-ubstituted N-tosylaziridines from (R,R,R,Ss)-(-)-sulfonium salt 2 (derived from Eliel s oxathiane see Section 1.2.1.1) and N-tosyl imines with use of phosphazine base (EtP2) to generate the ylide (Scheme 1.42) [67], Although the diastereoselectiv-ity was highly substrate-dependent, the enantioselectivities obtained were very high (98.7-99.9%). The chiral auxiliary, although used in stoichiometric quantities, could be isolated and reused, but the practicality and scope of this procedure is limited by the use of the strong - as well as expensive and sensitive - phospha-zene base. 

Chiral sulfonium salts derived from oxathianes have been developed for stoichiometric epoxidation reactions. The sulfonium salts were deprotonated and allowed to react with a, 3-unsaturated aldehydes to give trons-vinylepoxides with excellent ees and transxis ratios (Scheme 9.16b) [76]. The yields were generally high [75], and the best results were obtained with Ar = 4-OMePh. 

A much more readily accessible chiral auxiliary is oxathiane 16, which can be smoothly synthesized from inexpensive (+)-pulegone (14)3S. 

Cleavage of the oxathiane moiety can be carried out with iV-chlorosuccinimide/silver nitrate and leads to the a-hydroxy aldehyde 21 along with a diastereomeric mixture of sultines 20. The sultines can be reduced to the hydroxy thiol 22 which can be reconverted to the chiral auxiliary 16 in ail overall recovery of about 70%39. 

Another chiral auxiliary used in diastereoselective addition reactions is the 1,3-oxazine derivative 4a which shows a close structural resemblance to the 1,3-oxathiane 16 (vide supra). However, in contrast to the oxathiane, 4a cannot be readily acylatcd in the 2-position. Therefore, the benzoyl derivative 4b was prepared by condensing amino alcohol 3 with phenylglyoxal. 

Stereochemically, even more interesting are the bis-l,3-oxathiane derivatives 98 and 99 <2005STC369>. All compounds are chiral and the chiral elements are carbons C-2/C-2 and the 1,3-oxathine moieties themselves (Equation 9). Due to the bis-structure, compounds 98 and 99 exhibit both homochiral iZR,2 R ZS,Z S) and hetero-chiral (2R,Z S) isomers (Scheme 4) and they reveal rapid equilibration in solution via open-chain intermediates, thereby preventing separation and individual analysis of the isomers in solution. In the solid state, the compounds crystallized either as unique heterochiral isomers or as a mixture of the two as a solid solution. 

Racemic 2-aryl-l,3-oxathianes have been oxidized to chiral, nonracemic sulfoxides using H202-urea as oxidant and Ti-salen complexes in catalytic amounts. High ee (94% at 41% conversion) was achieved by this method (Equation 43) <2003CH24>. 

New chiral auxiliaries for nucleophilic reactions have been prepared from 5-hydroxy-l-tetralone <2001TA2605> and myrtenal <2001TA3095> and their use in diastereoselective reactions has been evaluated. It was found that both the tetralone- <2003EJ0337, 2003JOC6619> and the myrtenal- <2003TA3225, 2005TA1837> derived 2-acyl-l,3-oxathianes reacted diastereoselectively with nucleophiles (Equations 60 and 61). 

Chiral bis-lithium amide bases have been used for enantiotopic deprotonation of the sulfonium salt of 1,4-oxathiane 86. The anion undergoes an enantioselective thia-Sommelet rearrangement to afford the 3-substituted-1,4-oxathiane 87. Only bis-lithium amide bases were effective, giving products with high diastereoselectivity and with low to moderate enantioselectivity (Equation 13) <2003TL8203>. 

An asymmetric synthesis of mevalolactone in over 87% e.e. employs a 1,3-oxathiane as the chiral auxiliary (81TL2859). The reagent (818), easily prepared from (+)-pulegone (81TL2855), was metallated with u-butyllithium and the anion reacted with acetaldehyde. Oxidation of the diastereomeric mixture of alcohols to the ketone (819) and reaction of... 

A number of attempts have been made to use optically active sulfur ylides to transfer the chirality of sulfur to carbon in the formation of epoxides and cyclopropanes. The results were somewhat disappointing. Thus, virtually no asymmetric induction was observed with the ylide (1) [475]. With the stabilized ylides (2), e.e. values in the range 7-43% were reported [476]. Better results were obtained with sulfonium ylides derived from Eliel oxathiane [477]. Optically active diaryl epoxides could be prepared under PTC in high yields and good e.e. values. 

CHIRAL 1,3-OXATHIANE FROM (+)-PULEGONE HEXAHYDRO-4,4,7-TRItCTHYL-4H-l, 3-BEN 2DXATHIIN (4H-1,3-Benzoxathiin, hexahydro-4,4,7-trimethyl-)... 

Reversal of diastereoselectivity of reactions with RMgX and RLi.1 The chiral 2-acyl- 1,3-oxathiane 1 (12, 237-239) undergoes diastereoselective addition of... 

The aldol reaction of dithioester enethiolates has been used for the synthesis of dithiolactones [123], chiral substrates for the Claisen rearrangement [124, 125], and oxathianes [126]. Thioamide enethiolates may be employed in this reaction as well as shown with /Tthiolactams [26], or with a precursor of the antitumour agent vinblastine [127]. 

The optically active 1,3-oxathiane derivative 81, synthesized as a chiral auxiliary (cf. Scheme 30), has been reported. The isomers were assignend by X-ray diffraction in the solid state trans) and by NOE experiments in solution cis) (97CPB778). Rules for the specification of the absolute configuration of the enantiomers R or S) for 1,3-oxathianes and other heterocycles with at least two hetero atoms were proposed and proved... 

Chiral tertiary u-hydroxy aldehydes This chiral 1,3-oxathiane (1) undergoes the highly selective reactions shown by 4,4,6-trimethyl-1,3-oxathiane (this volume) to give the optieally aetive oxathiane carbinols 3 in greater than 90% diastereomeric purity. These are cleaved by NCS antj silver nitrate (4, 216) to a-hydroxy aldehydes (4) and a sultine. which can be converted back to 1 (95% yield). The a-hydroxy aldehydes (4) are unstable... 

The reaction of a chiral Grignard reagent derived from ephedrine with the oxathiane 2 was used to prepare the 8-hydroxy acid 5 in 34% overall yield. On standing, 5 lactonizes to (— )-malyngolide (6). ... 

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