Cyclohexenone sulfoxide

The lithium enolate of methyl trimethylsilyl acetate adds to cyclopentenone and cyclohexenone sulfoxides by the nonchelate model with good to excellent selectivity, as shown in Scheme 5.42a [210]. After the Michael addition, the sulfoxide and trimethylsilyl groups are removed, and the selectivity is assessed by determining the... 

In contrast to allylic phosphine oxides, phosphonates, sulfones and sulfoxides, the chemistry of lithiated allylic sulfoximines has been less extensively developed25 27. The reaction of lithiated racemic A-phenyl-A -(4-rnethylphenyl)-S -(2-propenyl)sulfoximine with either 2-cy-clopentenone or 2-cyclohexenone gave a complicated mixture with 1,4-oc-ad ducts being slightly favored over the 1,4-7-adducts. The yields of these adducts were poor25. In contrast, lithiated racemic Ar-tert-butyldiphenylsilyl-5-phenyl-5,-(2-propenyl)sulfoximine gives mainly 1,4-y-ad-ducts on reaction with the same enones26. 

Except for the syntheses using terpene-derived starting materials (Schemes 13.7, 13.8, and 13.9), the previous juvabione syntheses all gave racemic products. Some of the more recent juvabione syntheses are enantiospecific. The synthesis in Scheme 13.16 relied on a chiral sulfoxide that undergoes stereoselective addition to cyclohexenone to establish the correct relative and absolute configuration at C(4) and C(7). The origin of the stereoselectivity is a chelated TS that leads to the observed product.20... 

Stereochemistry of this reaction is also quite interesting. Thus, both geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides (165-167) were synthesized from 2-cyclohexenone, methyl vinyl ketone and 2-heptanone respectively, and the corresponding magnesium alkylidene carbenoids were generated and treated with A-lithio aniline or A-lithio 1-aminonaphthalene. The results are summarized in Table 9. 

Diastereoselective reduction of chiral fl-keto sulfoxides1 (13, 115-116). This reaction, which can be controlled to provide either diastereomer of a chiral P hydroxy sulfoxide, has been used to obtain (R)- or (S)-4-hydroxy-2-cyclohexenones from the monoketal (2) of 1,4-cyclohexanedione. Sulfinylation of 2 with (S)-( —)-... 

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), ... 

In addition, the 1,4-addition reactim of the anion (87) derived from various cyclic allylic sulfoxides with 2-cyclq)entenones (88) were investigated (Scheme 24). Methyl substitution at C-3 of (88) hinders the 1,4- dition. An activate enone (88e), however, affords excellent chemical and optical yields of the 1,4-adducts (89). (-i-)-12,13-Epoxytrichothec-9-ene (91) and its antipode have been enantioselectively synthesized tom (S)-4-methyl-2-cyclohexenone (90) in 11 steps (Scheme 25). ... 

In contrast to cyclohexenone, the unsaturated sulfoxide proved to be an excellent substrate for the [3 + 2] cycloaddition. The reaction was carried out in refluxing toluene using a catalyst derived from palladium acetate and triisopropyl phosphite, the latter acting both as a reducing agent and as a ligand. 

Alkyl- X-cyclopentenones 6-aIkyl-ii-cyclohexenones. Grieco and Pogonowski have described a route to 5-alkyl-A -cyclopentenones from cyclo-pentanone, the first step of which is sulfenylation with diphenyl disulfide and LDA followed by periodate oxidation to the fi-keto sulfoxide (1). This product is converted into the dianion with 2 eq. of Uthium diisopropylamide the dianion... 

The procedure for oxidation of the sulfide to the sulfone is based on that reported earlier by Bordwell and Pitt. The synthetic utility of phenyl vinyl sulfone and sulfoxide derives not only from their ability to serve as excellent Michael acceptors toward such reagents as enolate anions and organometallics, but also as moderately reactive dienophiles in Diels-Alder reactions. " The resulting adducts, in turn, can be chemically modified so that these electron-deficient olefins serve as useful synthons for acetylene,ethylene,terminal olefins,vinylsilanes, and ketene in [4 + 2] cycloadditions. Phenyl vinyl sulfone undergoes ready cycloaddition to Danishefsky s diene in the first step of a protocol for the regiospecific y-alkylation of 2-cyclohexenones. Furthermore, the ready lithiation of phenyl... 

The diastereoselectivity observed for the conjugate addition to the nonchelated enone sulfoxide (98a) was improved by the use of diorganomagnesium reagents with DME as solvent. Under the same reaction conditions, nucleophilic additions to the corresponding cyclohexenone (101) proceeded with moderate stereoselectivity, giving cyclohexanones (102) as products with somewhat lower enantiomeric excesses than for cyclopentanones (99b) (Scheme 5.35 and Table 5.4) [99]. It should also be noted that in several cases the addition of a highly complexing additive such as 18-crown-6 served to raise the amount of asymmetric induction by about 20% (Table 5.4). 

Mori was clearly intrigued by juvabione. Nearly 25 years after his first synthesis, his group described the third conjugate addition approach we will consider. This synthesis addresses both relative and absolute stereochemistry problems. The plan was to prepare the anion derived from vinyl sulfoxide 149 and examine its reaction with cyclohexenone (127). There was precedence for the 7-carbon of this type of allylic anion to behave as the nucleophile in conjugate additions (Hua). The hope was that this addition would take place with good diastereoselectivity and that the sulfoxide would influence the absolute stereochemistry of the process. 

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