Sulfoxides, cyclopentenone

The addition of the anion of the racemic 2-methyl-2-propenyl sulfoxides, rac-2-methyl-3-(phenyl-sulfinylpl-propene and /w-3-(rerr-butylsulfinyl)-2-methyl-l-propene to 2-cyclopentenone gives mixtures of (E)- and (Z )-y-l, 4-addition products which are a mixture of diastereomers at sulfur2. The (T )-products usually predominate, with the relative proportions of the (Z)-product increasing as the reaction temperature is increased. No asymmetric induction originating from the stereocenter at sulfur was observed when the sulfoxide substituent was phenyl however, there was a marginal improvement in the case of the (Zi)-product when the sulfoxide substituent was ferf-butyl. 

The addition of the anion of the 1,3-dimethyl-2-butenyl sulfoxides to 2-cyclopentenone was examined2. The anion of rar-2-methyl-4-(phenylsulfinyl)-2-pentene gave a 50 50 mixture of ( )- and (Z)-y-1,4-adducts which differed in the relative configuration of the new stereocenter regarding the stereocenter at sulfur. That is, for either the (Z)- or the ( )-product there is complete asymmetric induction from the stereocenter at sulfur, but in the opposite direction. When the rm-butyl analog, ruc-4-(/wt-butylsulfinyl)-2-methyl-2-pcntcne, was reacted, it gave exclusively the ( )-adduct, likewise as a single diastereomer. 

The 1,4-addition of the anion of a racemic /1-oxo sulfoxide to racemic 2-cyclopentenone was reported to give a single diastereomeric adduct resulting from addition opposite to the y-ace-toxy group20, t he relative configuration of the exocyclic stereocenter was not determined. 

Extension of these studies to the more sterically demanding allylic sulfoxide anion derived from T(/e/7-butylsulfinyl)-l-(2-methylpropyl)-2-butene on reaction with 2-cyclopentenone gave three diastcrcomcric 1,4-adducts, 3-[3-(7( rt-butylsulfinyl)-l, 5-dime thy lhexyl]cyclopentanones, in a ratio of 31 26 4333. 

The addition of the anions of racemic cyclic allylic sulfoxides to various substituted 2-cyclopentenones gives y-l,4-adducts as single diastereomeric products22. The modest yields were due to competing proton-transfer reactions between the anion and enone. The stereochemical sense of these reactions is identical to that for the 1,4-addition reaction of (Z)-l-(/erf-butylsulfinyl)-2-methyl-2-butene to 2-cyclopentenone described earlier. 

To a cold (—78 C) solution of 0.8 g (3.9 mmol) of 3-(phenylsulfinyl)-l-cyclohcxcnc in 20 mL of THF is added a cold ( — 78 lC) solution of 4.37 mmol of LDA in 20 mL of THF via a cannula. The resulting yellow solution is stirred at —78 C for 30 min, and then 0.7 mL (4.0 mmol) of HMPA is added, followed after 5 min by the addition of 0.320 g (3.9 mmol) of 2-cyclopentenone, and the solution is stilted at —78 C for 15 min. A solution of 0.26 mL of acetic acid in 2 mL of diethyl ether is added and the solution warmed to 25 C, diluted with aq NH4C1, and extracted with three portions ol diethyl ether. The combined extracts are washed with aq NaCl, dried over MgSC)a, concentrated, and column chromatographed to give the title compound yield 0.562 g (50%). Starting sulfoxides and enones were also recovered. 

From studies on the addition of racemic allylic sulfoxide anions of 3-substituted l-(phenyl-sulfinyl)-2-propenes to racemic 4-tcrr-butoxy-2-cyclopentenone, it was found that (El-allylic sulfoxides give. vyw-products, and (Z)-allylic sulfoxides give anti-productsx. 

From single-crystal X-ray structural analysis the ground-state conformation of (.S )-2-(4-meth-ylphenylsulfinyl)-2-cyclopentenone was shown to have the sulfoxide bond orientated anti to the carbonyl bond, as expected for minimization of electrostatic interactions13. 

Alkenyl sulfoxides 177 and 178, which can be readily prepared from 1-alkynes222, provide synthones for the carbocations 179 and 180. These synthones are useful for the simple construction of cyclopentenones and also in providing an electrophilic precursor for the jS-side-chain on prostanoids223,224. 

When enantiomerically pure allyl p-tolyl sulfoxide is deprotonated and then treated with electrophilic 2-cyclopentenone, a conjugate addition occurs forming a new carbon-carbon bond with very high control of absolute stereochemistry (equation 25)65. See also Reference 48. Similarly, using more substituted enantiomerically pure allylic sulfoxides leads to virtually complete diastereocontrol, as exemplified by equations 26 and 27 the double bond geometry in the initial allylic sulfoxide governs the stereochemistry at the newly allylic carbon atom (compare equations 26 vs. 27)66. Haynes and associates67 rationalize this stereochemical result in terms of frontier molecular orbital considerations... 

This type of asymmetric conjugate addition of allylic sulfinyl carbanions to cyclopen-tenones has been applied successfully to total synthesis of some natural products. For example, enantiomerically pure (+ )-hirsutene (29) is prepared (via 28) using as a key step conjugate addition of an allylic sulfinyl carbanion to 2-methyl-2-cyclopentenone (equation 28)65, and (+ )-pentalene (31) is prepared using as a key step kinetically controlled conjugate addition of racemic crotyl sulfinyl carbanion to enantiomerically pure cyclopentenone 30 (equation 29) this kinetic resolution of the crotyl sulfoxide is followed by several chemical transformations leading to (+ )-pentalene (31)68. 

Enantiomerically pure 3-tolyl-2-sulfinyl-2-cyclopentenone 37 undergoes smooth, mild and diastereoselective conjugate hydride addition with lithium tri(sec-butyl)borohydride to afford ultimately 3-tolylcyclopentanone 38 in 93% enantiomeric purity (equation 35)78. The absolute stereochemistry of product 38 is consistent with a chelated intermediate directing hydride addition from that diastereoface containing the sulfoxide lone pair. 

An intramolecular version of enolate Michael addition to enantiomerically pure vinylic sulfoxides is represented by reaction of a cyclopentenone sulfoxide with dichloroketene (Scheme 5)90 this type of additive Pummerer rearrangement has been developed by Marino and coworkers91 into a highly effective way of constructing variously substituted lactones in very high enantiomeric purity (equation 43). 

In a similar manner, Brummond et al. demonstrated the first total synthesis of 15-deoxy-A12,14-prostaglandin J2 (162) that was completed using a silicon-tethered allenic Pauson-Khand reaction to obtain the highly unsaturated cyclopentenone substructure [36]. Treatment of alkynylallene 160 with molybdenum hexacarbonyl and dimethyl sulfoxide affords the desired cycloadduct 161 in 43% yield (Scheme 19.30). Trienone 161 was obtained as a 2 1 Z E mixture of isomers in which the Z-isomer could be isomerized to the desired E-isomer. The silicon tether was cleaved and the resulting product converted to 15-deoxy-A12,14-prostaglandin J2 (162). 

Several reports have appeared on the effect of additives on the Pauson-Khand reaction employing an alkyne-Co2(CO)6 complex. For example, addition of phosphine oxide improves the yields of cyclopentenones 119], while addition of dimethyl sulfoxide accelerates the reaction considerably [20]. Furthermore, it has been reported that the Pauson-Khand reaction proceeds even at room temperature when a tertiary amine M-oxide, such as trimethylamine M-oxide or N-methylmorpholine M-oxide, is added to the alkyne-Co2(CO)6 complex in the presence of alkenes [21]. These results suggest that in the Pauson-Khand reaction generation of coordinatively unsaturated cobalt species by the attack of oxides on the carbonyl ligand of the alkyne-Co2(CO)6 complex [22] is the key step. With this knowledge in mind, we examined further the effect of various other additives on the reaction to obtain information on the mechanism of this rearrangement. 

The reaction using 11a as a substrate in the presence of several oxides as additives revealed that addition of tributylphosphine oxide, hexamethylphos-phoric triamide, and dimethyl sulfoxide all accelerate the reaction considerably. Furthermore, when about 10 molar amounts of N-methylmorpholine M-oxide (NMO) is added to the alkyne-cobalt complex 12b in THF,the reaction proceeds even at room temperature and cyclopentenone 13 b is obtained in 37% yield accompanied by another rearranged product, the methylenecyclobutanone 35, obtained in 23% yield as a mixture of ( )-and (Z)-isomers (Scheme 14). These facts indicate that dissociation of the carbonyl ligand of the alkyne-cobalt complex 12 is the rate-determining step in this rearrangement. This is also supported by the fact that under a CO atmosphere in refluxing THF the reaction is completely suppressed. 

Recently, it has been reported that sulfenic acids add readily to 1-alkynes to give a,(3-unsaturated sulfoxides,556 themselves useful for the synthesis of various cyclopentenones (equation 307).557... 

The synthesis of 3 was initiated by reaction of wBuLi with the protected cyclopentenone 2 generating the corresponding vinyllithium reagent by halogen-metal exchange. Subsequent condensation with (S)-(-)-menthyl para-toluenesulfinate (13) provides the enantiodefined sulfoxide substituent in 3.5 Since thermal equilibration of chiral sulfoxides at room temperature is slow, the large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into carbon compounds. 

The P-addition of alkyl radicals to 4-methyl-2-(arylsulfinyl)-2-cyclopentenone 117 has been shown to occur in a completely stereocontrolled manner. Of a mixture of (4/ )- and (45)-117, only (4R)-117 reacts with t-Bu and i-Pr radicals to give the trans adducts 119a and 119b in 99% yield, while (45)-117 remained entirely unreacted. The stereochemical outcome of the reaction shows that the alkyl radical approaches from the side opposite to the aryl moiety in an antiperiplanar orientation to the carbonyl and sulfoxide bond. The 2,4,6-triisopropylphenyl group on sulfur plays a critical role, as it effectively shields the olefin face at the P-position by one of the isopropyl groups. This was confirmed by the 1 1 diastereomeric mixture obtained in the reaction of 4-methyl-2-(p-tolylsulfmyl)-2-cyclopentanone with the tert-butyl radical. 

Use of the chiral carbon pool for cyclopentenone preparation is also known. The fungal metabolite terrein [88] was selectively monoacetylated and then reduced with chromous chloride to enone [89]. Acetylation and olefin cleavage with ruthenium tetroxide aiwi sodium periodate led to aldehyde [90], which was readily decarbonylated to [65] (51). An alternative route (52) began with the less common S,S-tartaric acid [91], converted in four steps to diiodide [92]. Dialkylation of methyl methylthiomethyl sulfoxide with [92] gave the cyclopentane derivative [93]. Treatment of [93]... 

In preliminary reports, the y-carbon of the carbanion of allyl phenyl sulfoxide has been shown to attack cyclopentenone and cyclohexenone by 1,4-addition to deliver vinyl sulfoxides. " The lithiated carbanion (75) of l-(phenylsulfinyl)-2-octene ( Z = 85 15) adds to 4-(-butoxycyclopent-2-en-l-one (74) to give jy -( )-vinylic sulfoxide (76) and anti-( )-vinylic sulfoxide (77) in the ratio of 79 21. It has been suggested that (76) arises almost exclusively from the ( )-(75), and (77) derives from the (Z)-(75). Both the products have the same geometry about the double bond, but differ in configuration at the allyiic carbon atom (equation 21), ... 

An example of sulfinate functioning as a leaving group is shown in equation (16), ° while another forms the basis of a useful synthesis of 3-cyclopentenones (Scheme 22). Zwanenburg has reported a transformation related to the Ramberg-Backlund reaction in which the halide leaving group is replaced by sulfinate and, in addition, the usual sulfone is replaced by sulfoxide. ... 

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