Dithiolane 1,3-Dioxide

The scope and limitations of the metal anions of 2-halo-1,3-dithiane trans- 1,3-dioxide as diastereoselective carbonyl anion equivalents has been explored with regard to reaction with aldehydes.79 Reactions of metallated trans-1,3-dithiolane 1,3-dioxide (five-membered ring) with aldehydes under kinetic and thermodynamic control have also been studied and contrasted with those of the metallated monooxide, parent sulfide, and 1,3-dithiane 1,3-dioxide (six-membered ring).80... 

Dithiolane 1,3-dioxide 363, prepared in 84% yield by oxidation of 1,3-dithiolane 362 with MCPBA <1998JOC3481, 1998J(P1)2771>, was smoothly converted to the dimethylamino derivative 364 in 100% yield. Hoffman elimination using methyl iodide and Hilnig s base at room temperature gave 365 in 86% yield (Scheme 46). 

The 1,3-dithiolane 1,3-dioxide 365 was also investigated in the Diels-Alder reaction with a range of simple dienes (cyclopentadiene, 1-methoxybutadiene, l-methoxy-3-trimethylsilyloxybutadiene, furan) <1995JOC4962, 1998J(P1)2771> and 1,3-dipolar cycloadditions with A - /t-butyl-(7-phenyl nitrone <1998JOC3481> or 3-oxidopyr-idinium betaines <20030BC1884>. 

Synthesis. First obtained and described by Bennett and Statham in 1931, racemic trans-1,3-dithiolane 1,3-dioxide can be conveniently prepared in a good yield (83%) by m-CPBA oxidation (eq 1) of 1,3-dithiolane in dichloromethane or ether, and with complete stereoselectivity (no meso adduct). 

Enantiopure Trans-1,3-dithiolane 1,3-dioxide has been reported. It could be isolated after recrystallization of 54% enan-tioenriched product which was a very minor side-product of the monoxidation of 1,3-dithiolane by Aspergillus foetidus. So far, no viable pathway to the enantiopure derivatives has been devised. 

Anionic Additions to Aldehydes. The /dCa of trans-, >-dithiolane 1,3-dioxide has been determined by Bordwell and disclosed by Aggarwal to be 19.1, a surprisingly low value compared to Trans-1,3-dithiane 1,3-dioxide (24.9). While the deprotonation of 1,3-dithiolane and 1,3-dithiolane 1-oxide leads to unstable carbanions that cleave, the anion of Trans-1,3-dithiolane 1,3-dioxide has shown sufBcient stability to undergo addition reactions with aldehydes. Moreover, because of the Cj-symmetry incorporated into a five-membered ring, its potential to serve as a chiral acyl anion equivalent has been tested. 

Related Reagents. Several other chiral acyl anion equivalents have been published. Conqtarison with 1,3-disulfur derived compounds is reported below. Benzaldehyde has been taken as the reference electrophile. The equivalents are of two kinds mono-and dioxides. Generally, monoxides are slightly less efficient (85 15 ds) or much more difficult to prepare and thus of scarce synthetic interest (100 0 ds). Furthermore, they lead to additional problems because they lack C -sjunmetry. Dioxides are either cyclic or acyclic. Acyclic bis(sulfoxides) work also slightly less efficiently with benzaldehyde (90 10 to 95 5 ds), but slightly better with aliphatic aldehydes. The two reported cyclic dioxides (trans-l,3-dithiane 1,3-dioxide and trans-1,3-dithiolane 1,3-dioxide) are comparable and work equally well (>98 2 ds). Yet, there are some differences trans-1,3-dithiolane 1,3-dioxide proceeds under kinetic control, while trans-1,3-dithiane 1,3-dioxide is best under thermodjuiamic conditions. The latter also offers the advantage to be available in enantioenriched form. 

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

Thietanes can also be prepared by ring contraction of higher-membered heterocyclic rings. Thermolysis of the dithiolane dioxide 129 in benzene leads to trans-2-phenyl-3-benzoylthietane (130) and benzalacetophenone (Eq. 20). 

Advances in synthesis and research of oligomeric tetrathiafulvalenes 97MI9. Enantioselective oxidation of 1,3-dithiolanes to corresponding S-oxides and S,S-dioxides by designer yeast 99JHC1533. 

Various chiral dipolarophiles have been used in the asymmetric synthesis of hexahydro-isoxazolo[2,3- ]pyridines. Examples include // / -2-methylcnc-l, 3-dithiolane 1,3-dioxide 83 <1998JOC3481>, chiral vinyl sulfoxide 85 <1997TA109>, or chiral dioxolanes <2001TA1747> (Scheme 27). 

A [5 - 2 + 2 + 1] fragmentation followed by cyclization forming a new five-membered ring was observed by FVP studies of 2-propenyl-l,3-dithiolan 1,1-dioxide (79) (95H1967). The reaction mixture consists of four products thiophene (26%), 2,5-dihydrothiophene (80,34%), 4-methyl-2-propenyI-4//-l,3-dithiine (20%), and 2,6-dimethyl-2//,6//-l,5-dithiocine (20%). The last two compounds are formed by [4 + 2] or [4 + 4] dimerization of the intermediate 2-butenethial. Formation of 80 involves a 1,5-H shift of the as-butenethial, followed by cyclization. 

Pyrolytic methods involve the use of dithiolane S, S -dioxides as starting materials which, upon heating, afford reactive thioaldehydes, such as trifluorothioacetaldehyde, trapped as the Diels-Alder adduct369,370 (equation 82). In equation 80 an enethiolate was formed, and this feature has been employed also in the cleavage of the oxathiolane 78. The silver vinylthiolate 79 thus obtained was applied in the preparation of new antibacterial cephem derivatives371. 

In what is effectively a desulfurization reaction, 1,2-dithiolane 1,1-dioxide reacts exothermically with aminophosphines such as tris(diethylamino)phosphine in benzene solution to give 1,2-oxathiolane 1-oxide in excellent yield (71JOC322). The reaction, which requires a slight excess of the aminophosphine, is shown in Scheme 41. 

The photolysis of 4-phenyl-l,2-dithiole-3-thione (71) gives a dimer (72) (73TL1561), but benzo-l,2-dithiolane 2,2-dioxide (73a) gives an o-thioquinone methide (74) (78JOC3374). 

Heterocycles of this type occur widely. The benzo[l,3]dioxole ring system is often found in natural products and their degradation products, e.g., sesamol 38 lipoic acid 39 is a naturally occurring 1,2-dithiolane derivative. The 1,3-dithiolanes 40 are commonly known as 1,3-dithioacetals and have been extensively used in carbonyl group chemistry. In the absence of cyclic conjugation, ring sulfur atoms can readily exist in higher oxidation states as, for example, in the oxathiole S, -dioxide 41. 1,3,2-Dioxathiolane A-oxides 42 (cyclic sulfites) and 1,3,2-dioxathiolane A,A-dioxides (cyclic sulfates) are useful as synthetic equivalents of epoxides. 

The sulfur in 1,2-dithiolanes is nucleophilic and can be alkylated to form 1,2-dithiolanium salts (527 528). S-Oxidation and/or formation of sulfones of thiazolidines results in certain situations, for example, with penams <2001BMC2113>. Pyrolysis of thiazolidin-2-one 1,1-dioxides results in loss of SO2 and the formation of -lactams < 1997J (P 1)2139 >. 

The lower levels of stereocontrol which are often observed in the 1,3-dipolar cycloaddition of acyclic nitrones, as opposed to cyclic nitrones, could be accounted for by the possibility of interconversion of the nitrone geometry. One innovative solution to this problem is Aggarwal s recently reported 1,3-dipolar cycloadditions of the C2-symmetric cyclic alkenyl sulfoxide (l/ ,3/ )-2-methylene-1,4-dithiolane 1,3-dioxide (155) with acyclic nitrones.94 The presence of a C2 symmetry element in 155 means that the exo/endo approaches of 155 to a dipole are symmetry related and therefore identical, thereby reducing the number of possible transition states in the reaction. 1,3-Dipolar cycloaddition of 155 with nitrones 156a-c resulted in single diastereomeric 4,4-disubstituted isoxazolidine products (157a-c) (Scheme 42). Likewise 1,3-dipolar cycloadditions with other acyclic nitrones yielded single diastereomeric products. 

Ketene equivalents have found widespread use as partners in Diels-Alder reactions for the construction of cyclic, fused, and bridged unsaturated ketones. However, ketene equivalents based on simple vinyl sulfoxides are poor dienophiles and show low levels of diastereocontrol. Recently, Aggarwal and colleagues reported that (l/ ,3/ )-2-methylene-l,3-dithiolane 1,3-dioxide (187) was a highly reactive and highly selective chiral ketene equivalent.116 Diels-Alder cycloaddition of this... 

Thioketen Cyan-phenyl- Ell, 242 [aus 2-(os-CN —benzyliden)-l,3-dithiolan-2,2-dioxid]... 

Another example which illustrates the importance of the structure of the diazoalkane in reactions of thiocarbonyl compounds and derivatives thereof is the reaction of trithiocarbonate S,S-dioxide 6 with diazomethane and phenyldiazomethane52. Whereas the former gives the dithiolane derivative 7, the latter affords the thiirane 8. Both reactions are, however, fully stereoselective affording single diastereomeric compounds the most probable structures are depicted in the scheme. 

It has also been reported [30] that a large number of 1,3-dithiolanes 70 were efficiently reconverted to the parent carbonyls 71 upon treatment with a 5-molar excess of selenium dioxide in acetic acid at room temperature for 1 - 2 h... 

Ethenyl-l,3-dithiolane 1,1-dioxides 367 were prepared by oxidation of the 2-ethenyl-l,3-dithiolane 366 using the catalytic 0s04/Me3N0 system (Equation 46) <1995H(41)1967>. 

The reaction of an ethanol solution of stoichiometric amounts 3-oxo-2,3-dihydrothiophene 1,1-dioxide 646 with 1,2-ethanedithiol in the presence of pyridine provided 1,3-dithiolane 647 in 93% yield. The same reaction performed with 2 equiv of 1,2-ethanedithiol and PTSA as a catalyst afforded the bis-l,3-dithiolane 648 in 93% yield (Equations 89 and 90) <1996TL119, 1999J(P1)3085>. 

Thermolysis of 4-benzoyl-3-phenyl-l,2-dithiolane 2,2-dioxide at 230° in a sealed tube gives 3-benzoyl-2-phenylthietane in 55% yield. ° Photolysis of 1,2-dithiolanes gives low yields of thietanes. ... 

The first thiete fused to an aromatic system 219 (and an anthracene derivative) was reported in 1965 and was prepared by reduction of a naphthothiete sulfone. An attempt to prepare benzothiete by desulfurization of benzo-l,2-dithiolane was unsuccessful. Photolysis of benzo-l,2-dithiolane 1,1-dioxide in an attempt to extrude sulfur dioxide to give benzothiete also was unsuccessful. The naphthothiete 205, however, was prepared by extrusion of sulfur dioxide from 220 and nitrogen from 221. Thiete 205 also is obtained in 6-8% yield by treatment of 1,8-dehydronaphthalene with carbon disulfide. The unstable thiolactone 211 was formed by a photochemical extrusion of benzaldehyde from 222 and from 222a at 350°C. The benzothietes 209, 223, " and 224 have been... 

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