Sulfonium ylides addition reactions

Oxiranes can be prepared in excellent yield from carbonyl compounds by alkylidene transfer with sulfonium ylides. The reaction is generally carried out with dimethylsulfonium methylide 77, dimethylsulfoxonium methylide 78, or related compounds such as anionoid species originating from sulfylimines 79 and sulfox-imines 80 that can undergo addition to the electrophilic carbonyl carbon. 

Diphenylcyclopropane has been prepared previously by (1) the Simmons-Smith procedure (24% yleld) b,19 and modified versions of this method (up to 72%),20 (2) sulfonium ylide addition to 1,1-diphenylethene (61% yield),21 (3) reduction of 1,1-diphenyl-2,2-dihalocyclopropanes with sodium in ammonia (47% yield),22 with sodium and tert-butyl alcohol (80%), or with diethyl lithiomethanephosphonate (62%),23 (4) base-promoted cyclization of trimethyl(3,3-diphenylpropyl)ammonium iodide (78%),24 (5) boron trifluorlde-promoted cyclization of a corresponding 3-hydroxypropyistannane (97%),2 (6) reaction of 3,3-diphenylpropenoic acid with lithium aluminum hydride (62%),2 (7) reaction of... 

It is also possible to convert carbonyl groups into oxirane rings with cenain carbenoid synthons. The classical Darzens reaction, which involves addition of anions of a-chloroacetic esters, has been replaced by the addition of sulfonium ylides (R. Sowada, 1971 C.R. Johnson, 1979). 

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Durst [478, 479] has shown that the sulfonium ylide (3) transfers its benzylidene group to some carbonyl compounds with e.e. values approaching enantiomeric purity, although the reaction was not yet amenable to synthetic utility (low overall yields, side reaction). However, an interpretation of the difference of behaviour of (3) and (4) towards PhCHO (e.e. values, respectively, 96% and less than 3%) led the authors to propose a [2 + 2] cycloaddition mechanism rather than the commonly accepted nucleophilic antiperiplanar addition for the reaction of a sulfur ylide with a carbonyl compound [479]. Clearly, more work is needed in this area. 

The synthetic utility of a-phosphorus- and a-thio-stabilized carbanions is the subject of numerous reviews.21 Notable are additions of phosphonium ylides (237),183 sulfonium ylides (238),l84 ° oxosulfo-nium ylides (239)184 " and sulfoximine ylides (240)184,1 to electron-deficient alkenes which afford nucleophilic cyclopropanation products. In contrast, with a-(phenylthio)-stabilized carbanions, which are not acyl anion equivalents, either nucleophilic cyclopropanation or retention of the hetero substituent occurs, depending on the acceptor and reaction conditions used. For example, carbanion (241) adds to 1,1-... 

Another widely used route to cyclopropanes involves the addition of sulfonium ylides to a,/ -unsaturated carbonyl compounds (S.R. Landor, 1967 R. Sowada, 1971 C.R. Johnson, 1973B, 1979 B.M. Trost, 1975 A). Non-activated double bonds are not attacked. Sterical hindrance is of little importance in these reactions because the C—S bond is extraordinarily long... 

Benzyl bromides 15 derived from either salicylaldehydes or 2-methylphenols by reaction with alkyl propynoates afford 277-1 -benzopyrans on treatment with tetrahydrothiophene and K2CO3. A sulfonium ylide is proposed which initiates a Michael addition - elimination -substitution sequence. When CS2CO3 is used as the base, 477-1-benzopyrans result almost exclusively, presumably through isomerisation of the 277-1-benzopyran. The protocol thus offers access to both chromene isomers through simple variation of the reaction conditions <06OL3853>. The Cu-catalysed intramolecular O-arylation of a-(2-bromobenzyl)-P-keto esters in refluxing THF offers a useful route to 2-substituted 477-l-benzopyran-3-carboxylates <06JOC6427>. 

Unstabilized sulfonium ylides and stabilized sulfoxonium ylides show different reactions with a,P-unsaturated carbonyl compounds the former give epoxides and the latter give cyclopropanes. The epoxide formation (i.e. 1,2-addition) is kinetically favourable while cyclopropane formation (i.e. 1,4-addition, Michael addition) is energetically favourable. 

Oxosulfonium ylides as well as sulfonium ylides stabilized by an electron-withdrawing group, such as an acyl , an alkoxycarbonyP , a cyano " and one of their vinylogues satisfactorily cyclopropanate a variety of Michael acceptors (e.g., equation 81) . In these reactions, the 1,2-addition is usually a minor pathway. Ylides stabilized by two... 

In the first step of this reaction sequence, the primary alcohol 21 is oxidized to the corresponding aldehyde 38 in a Parikh-Doering oxidation which is related to the Swern oxidation. In general, this type of oxidation is conveniently carried out by addition of a solution of pyridine-SOs complex in DMSO to a mixture of the alcohol, DMSO and NEts. It can be assumed that dimethyl sulfoxide and sulfur trioxide react to form 0-dimethylsulfoxonium sulfate 40, which then further reacts with primary alcohol 39 to give 0-alkyl dimethylsulf-oxonium intermediate 41. Then, sulfonium salt 42 is formed and subsequently deprotonated by NEts to give sulfonium ylide 43. Finally, an intramolecular p-elimination occurs to provide the desired aldehyde 44 and dimethyl sulfide. 

This reaction illustrates the stabilising effect exerted by the sulfonium centre on the adjacent double bonds. Isomeric allenes (32) may be similarly obtained from propargylic sulfonium salts (33) (Scheme 18). The allene (32), by treatment with diethyl sodiomalonate (34), followed by addition and rearrangement of the derived sulfonium ylide (35), affords the methyl sulfide (36) (Scheme 18). 

The two types of sulfur ylides also differ in their reactions with a,p-unsaturated carbonyl compounds. The highly reactive sulfonium ylides react rapidly by 1,2-addition across the carbon-oxygen double bond to yield the epoxides. On the other hand, the less reactive sulfoxonium ylides react by slower conjugate addition (1,4-addition) to give substituted ketocyclopropanes. Thus, dimethylsulfonium methylide (21) reacts rapidly with benzylideneacetophenone (chalcone) (37)... 

Cyclopropanation. The reaction of sulfonium ylides 96 with acrylic esters or methyl vinyl ketone provides rrany-2-arylcyclopropanecarboxylic esters and methyl ketones. Generation of the ylides with EtNP(NMe)2-N=P(NMe)j as base is convenient because dichloromethane can be used as solvent. Another synthesis of cyclopropanecarboxylates proceeds by a conjugate addition and 1,3-elimination sequence. ... 

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