Sulfones asymmetric synthesis

Deiana L, Zhao GL, Dziedzic P, Rios R, Vesely J, Ekstroem J, Cordova A. One-pot highly enantioselective catalytic Mannich-type reactions between aldehydes and stable a-amido sulfones asymmetric synthesis of 3-amino aldehydes and (3-amino acids. Tetrahedron Lett. 2010 51 (2) 234-237. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

For a review of the synthetic uses of 3-keto sulfoxides, sulfones, and sulfides, see Trost, B.M. Chem. Rev., 1978, 78, 363. For a review of asymmetric synthesis with chiral sulfoxides, see Solladie, G. Synthesis, 1981, 185. 

Chiral exocyclic alkenes such as 112, also having the chiral center two bonds away from the reacting alkene moiety, have been used in highly diastereoselective reactions with azomethine ylides, and have been used as the key reaction for the asymmetric synthesis of (5)-(—)-cucurbitine (Scheme 12.37) (169). The aryl sulfone 113 was used in a 1,3-dipolar cycloaddition reaction with acyclic nitrones. In 113, the chiral center is located four bonds apart from alkene, and as a result, only moderate diastereoselectivities of 36-56% de were obtained in these reactions (170). 

Asymmetric Synthesis of Allylic Sulfones and Allylic Sulfides and Kinetic Resolution of Allylic Esters... 

Scheme 2.1.4.8 Asymmetric synthesis of acyclic sulfones from carbonates.

When favorable results in the case of allylic sulfones had been obtained, asymmetric synthesis of the cyclic sulfides 5a, 5ba, Sab and Sea (Scheme 2.1.4.9) and of the acyclic sulfides 6aa, Gab, 6ac, 6ba, and 6bb (Scheme 2.1.4.10) was investigated. As shown by Table 2.1.4.9, the pyrimidyl sulfide Saa could be obtained in medium to good yield (entry 1). Interestingly, the corresponding pyridyl sulfide Sab isolated from the reaction of rac-laa with 2-pyridinethiol had a much lower ee value (entry 2). The reaction of the cycloheptenyl carbonate rac-lba with 2-pyrimi-dinethiol afforded the sulfide Sba in a similar yield to the cyclohexenyl derivative... 

The Pd-catalyzed allylic alkylation of sulfinate ions, thiols, and thiocarboxylate ions with racemic cyclic and acyclic allylic esters in the presence of bisphosphane BPA generally provides for an efficient asymmetric synthesis of allylic sulfones, sulfides, and thioesters. The Pd-catalyzed rearrangements of allylic sulfinates and allylic O-thiocarbamates, both of which proceed very efficiently in the presence of BPA, are attractive alternative ways to the asymmetric synthesis of allylic sulfones and allyUc thioesters also starting from the corresponding racemic alcohols. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolare (29) to the scalemic sulfoxide (30). Direct treatment of the crude Michael adduct with mew-chloroperbeuzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (31) X — a and ftH R = H in over 90% yield. 

An efficient asymmetric synthesis of the 3-substituted /3-sultams 163 has been reported. The key step of the synthesis is the Lewis acid-catalyzed aza-Michael addition of the enantiopure hydrazines (A)-l-amino-2-methoxy-methylpyrrolidine (SAMP) or CR,l ,l )-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]octane (RAMBO) to the alke-nylsulfonyl sulfonates 176. /3-Hydrazino sulfonates were obtained in good yield and excellent enantioselectivity. Cleavage of the sulfonates followed by chlorination resulted in the corresponding sulfonyl chlorides 177. The (A)-3-substituted /3-sultams 163 have been obtained in moderate to good yields and high enantioselectivity over two steps, an acidic N-deprotection followed by in situ cyclization promoted by triethylamine (Scheme 55) <2002TL5109, 2003S1856>. 

A large scale synthesis of a chiral tetrahydropyran derivative (five steps, 56% overall yield) from (+)-10-camphor-sulfonic acid has been described the sulfide is of value in the asymmetric synthesis of epoxides and aziridines <2006T11297>. 

During the past two decades, the asymmetric Diels-Alder reaction has become one of the most powerful tools in asymmetric synthesis as a result of its capacity to create up to four chiral centers in one step, often in a highly stereoselective manner. In the following sections, recent advances in this area using vinyl sulfoxide and vinyl sulfone dienophiles will be considered. It should be noted that, although beyond the scope of this review, many asymmetric Diels-Alder reactions of chiral sulfinyl-1,3-dienes have been reported.111... 

In the years to follow this chemistry was developed further and it turned out that especially the Pd(0)-catalyzed alkylation of sulfinate ions with racemic allylic carbonates provides an excellent means for the asymmetric synthesis of allylic sulfones [52-55]. Despite these successes the efforts to use 2-alkenylsulfinates as precursors for enantioenriched allylic sulfones never stopped [56]. 

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