Reactions sulfinylation

In order to make these oxidative reactions of 1,3-dienes catalytic, several reoxidants are used. In general, a stoichiometric amount of benzoquinone is used. Furthermore, Fe-phthalocyanine complex or Co-salen complex is used to reoxidize hydroquinone to benzoquinone. Also, it was found that the reaction is faster and stereoselectivity is higher when (phenylsulflnyl)benzoquinone (383) is used owing to coordination of the sulfinyl group to Pd, Thus the reaction can be carried out using catalytic amounts of PdfOAcji and (arylsulfinyl)benzoquinone in the presence of the Fe or Co complex under an oxygen atmosphere[320]. Oxidative dicyanation of butadiene takes place to give l,4-dicyano-2-butene(384) (40%) and l,2-dicyano-3-butene (385)[32l]. 

The N-oxides of isoquinolines have proved to be excellent intermediates for the preparation of many compounds. Trialkylboranes give 1-alkyl derivatives (147). With cyanogen bromide in ethanol, ethyl N-(l- and 4-isoquinolyl)carbamates are formed (148). A compHcated but potentially important reaction is the formation of 1-acetonyLisoquinoline and 1-cyanoisoquinoline [1198-30-7] when isoquinoline N-oxide reacts with metbacrylonitrile in the presence of hydroquinone (149). Isoquinoline N-oxide undergoes direct acylamination with /V-benzoylanilinoisoquinoline salts to form 1-/V-benzoylanilinoisoquinoline [53112-20-4] in 55% yield (150). A similar reaction of AJ-sulfinyl- -toluenesulfonamide leads to l-(tos5larriino)isoquinoline [25770-51-8] which is readily hydrolyzed to 1-aminoisoquinoline (151). 

Alkanesulfinyl chlorides have been prepared by the action of thionyl chloride on alkanesulfinic acids and by the solvolysis of alkylsulfur trichlorides with water, alcohols, and organic acids. The present procedure, which appears to be general for the preparation of sulfinyl chlorides in either the aliphatic or the aromatic series, is based on an improvement in the solvolysis method whereby the use of inert solvent is eliminated and the reaction is carried out in a one-phase system. ... 

From semiamidals, the correspondmg tnfluoromethyl substituted N-acyl mines [25, 28], 1,3-diambutadienes [27], N-sulfonyl mines [5, 29], N sulfinyl mines [30], and N-phosphoryl mines [31] can be obtamed in high yields on reaction with powerful dehydratmg realms like POC -pyndine or tnfluoroacetic anhydnde-pyndme [2, 5]... 

Sulfinyl azides have higher thermal stability than their divalent counterparts. For example, benzenesulfmyl azides ArS(0)N3 (Ar = Ph, 4-MeCelFt, 4-NO2C6H4), which are obtained by the metathetical reaction of the sulfinyl chloride and sodium azide in acetonitrile, can be stored in the solid state at low temperatures. ... 

Reactions with Sulfonyl Chlorides, Sulfinyl Chlorides,... 

The Darzens condensation reaction has been used with a wide variety of enolate equivalents that have been covered elsewhere. A recent application of this important reaction was appljed toward the asymmetric synthesis of aziridine phosphonates by Davis and coworkers.In this application, a THF solution of sulfinimine 34 (0.37 mmol, >98% ee) and iodophosphonate 35 (0.74 mmol) was treated with LiHMDS (0.74 mmol) at -78 °C to give aziridine 36 in 75% yield. Treatment of 36 with MeMgBr removed the sulfinyl group to provide aziridine 37 in 72% yield. 

A -sulfinyl chiral auxiliaries have been used to prepare enantiopure tetrahydro-P-carbolines and tetrahydroisoquinolines in good yields under mild reaction conditions. Both enantiomers of V-p-toluenesulfinyltryptamine 46 could be readily prepared from the commercially available Andersen reagents.Compound 46 reacted with various aliphatic aldehydes in the presence of camphorsulfonic acid at -78 °C to give the A-sulfinyl tetrahydro-P-carbolines 47 in good yields. The major diastereomers were obtained after a single crystallization. Removal of the sulfinyl auxiliaries under mildly acidic conditions produced the tetrahydro-P-carbolines 48 as single enantiomers. 

The activation energies were computed to 3.0 (toward 183), 0.3 (toward 182), and 21.8 kcal/mol (toward 184) at the B3-LYP/6-31G level, and thus the mechanism leading to 182 is the preferred one. The transition states of all three reactions belong to concerted but asynchronous reaction paths. The transacetalization of 177 with acylium cations results in the formation of the thermodynamically stabilized 187 (Scheme 121) [97JCS(P2)2105]. 186 is less stable than 187, and 185 is destabilized by 32.5 kcal/mol. Moreover, transacetalization of 177 with sulfinyl cations is not a general reaction. Further computational studies on dioxanes cover electrophilic additions to methylenedioxanes [98JCS(P2)1129] and the influence... 

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

The Stockman group has also studied reactions between the same imines and allyl sulfonium ylides (first reported by Hou and Dai [45]) [46], N-Sulfinyl vinylazir-... 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

Metalation ofa-sulfinyl dimethylhydrazones with terf-butylmagnesium bromide, butyllithium or lithium diisopropylamide, and reaction of the generated azaenolates with aldehydes, provides aldol adducts (e.g., 6) as mixtures of diastereomers. Reductive desulfurization leads to fi-hydroxy dimethylhydrazones (e.g., 7) which are cleaved to the desired /(-hydroxy ketones in 25% overall yield10 u. The enantiomeric excesses are about 50%, except for (- )-3-hydroxy-4-methyl-1-phenyl-1-pentanone (8) which was obtained in 88% ee. 

The first report on the addition of carbanions a-substituted by a chiral sulfinyl group to carbonyl functions described the reaction with symmetrical ketones3. It was found that meta-lation of ( + )-(S)-(methylsulfinylmethyl)benzene followed by quenching with acetone gives a mixture of diastereomeric /i-hydroxysulfoxides in a 15 1 ratio. This ratio depends on the presence or absence of extra lithium salts i.c., the source of the mcthyllithium used in deprotonation67. 

The reaction is believed to proceed via a six-membered cyclic transition state, analogously to the carbonyl addition of enolates, but the energy differences between boat- and chair-like arrangements are lower for x-sulfinyl carbanions69. Tor tert-butyl sulfoxides only anti- and, vn-products are obtained, arising from the approach onto the same diastereotopic face of the anion, but with different relative topicity. The exchange of lithium by zinc causes an increase of the anft-produci, but attempts to titanate the anion failed (see Table 3)69. 

More recently the stereoselectivity of the addition of sulfinyl anions to carbonyl groups was improved by introducing a sulfide group in the a-position30,31. The sulfoxide ( + )-(S)-(4-methylphcnylsulfinyl)(4-methylphenylthio)metliane was added to benzaldehyde to give the adduct 1 as a mixture of three diastereomers [(S5,15,27 )/(SS,17 ,2/J)/(S5,15,25) 55 30 15] which could be transformed into the corresponding a-methoxyaldehydc 4 in 67% yield with 70 % ee. The same reaction, when applied to phenylacetaldehyde, led to a product in 43 % yield with lower ee (46%). 

The addition of the dianion of /j-sulfmylcarboxylic acids to carbonyl compounds leads to the formation of the corresponding hydroxy derivatives which undergo spontaneous eyclization to give y-lactones. It was found that when optically active ( + )-(/ )-3-(4-methylphenylsulfinyl)pro-panoic acid is used for the reaction, the corresponding diastereomeric /i-sulfinyl-y-lactones are formed in a ratio which is dependent on the substituents of the carbonyl component. However, the diastereoselectivity was always moderate. 

To a solution of 0.6 g (2.8 mmol) of A -sulfinyl-4-toluenesulfonamide in 10 mL of dry CH,C1Z is added a solution of 2 mmol of aldehyde 1 in 2 mL of dry CI12CI2 at r.t. under argon protection. This mixture is stirred for 2-3 h (exception R1 = /-Pr, 48 h) before 6 mmol of the Grignard reagent is added at 22-30 C. After stirring for another 60 min the reaction is quenched with 50 mL of sat. aq NaCl and twice extracted with HtOAc. The combined extracts are dried over MgS04 and concentrated. Chromatography of the crude product on silica gel (pet. ether/EtOAc 2 1) affords 3a and 3b. 

Sulfinyl chlorides may be prepared from the corresponding thiols or disulfides by oxidative reactions rather than by reductions of sulfonyl compounds. A recent example, which improves the earlier procedure of Douglass, is given by equation (3)50. The chemistry of sulfinic acids and their derivatives has been reviewed51 52,53. 

Solladie and coworkers avoided the use of a sulfinyl chloride when they prepared (— )-menthyl 1-naphthalenesulfinate in an overall yield of 45% by the reaction of thionyl diimidazole, obtained from imidazole and thionyl chloride, with 0.7 equivalent of ( — )-menthol followed by 1 equivalent of 1-naphthylmagnesium bromide (equation 4). 

Active methylene compounds may be sulfinylated by reaction of their enolate anions with sulfinate ester7-1 This reaction has been investigated much in recent years and the compounds resulting from it have been of considerable use in asymmetric synthesis (see the chapter by Posner). Examples of the sulfinylation are given in the following paragraphs. 

Schneider and Simon82 prepared / -ketosulfoxides 47a and 47b by sulfinylation of the dianions of the methyl acetoacetates 48a and 48b with sulfinate ester 19 followed by decarboxylation of the intermediate products (Scheme 2). Apparently this avoids racemiz-ation experienced by others in the direct synthesis of these compounds9. /J-Ketosulfoxides are also available from the reaction of the anion derived from methyl p-tolyl sulfoxide with esters (see Section II.E). They can also be obtained, in some cases, through the hydrolysis of a-sulfinylhydrazones whose synthesis is described below. Mention has already been made of the synthesis of 2-p-tolylsulfinylcycloalkanones such as 32. 

Enolates derived from various imino compounds have been sulfinylated in reactions analogous to those shown by equations (14) and (15). Some representative examples are shown in equations 16-18. Here again, these compounds have been utilized in asymmetric syntheses. Addition of sulfinate ester 19 to a THF suspension of a-lithio-N,N-dimethylhydrazones, derived from readily available hydrazones of aldehydes and ketones, leads to a-sulfinylhydrazones in good yield, e.g. 53 and 54 (equations 16 and 17)85,86. Compounds 53 and 54 were obtained in a 95/5 and 75/25 E/Z ratio, respectively. The epimer ratio of compound 53 was 55/45. Five other examples were reported with various E/Z and epimeric ratios. 

In this chapter it is clearly impossible to do more than sample the extensive literature on the carbon acidity of sulfinyl and sulfonyl compounds, as it illuminates the electronic effects of these groups, particularly in connection with linear free-energy relationships. There are three main areas to cover first, as already indicated, equilibrium acidities (pKa values) second, the kinetics of ionization, usually studied through hydrogen isotopic exchange and finally, the kinetics of other reactions proceeding via carbanionic intermediates. 

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