Carbanions Claisen rearrangement

The intermediate product 162, formed from the nudeophilic addition of 1,2-alle-nic phosphonate or 1,2-allenic phosphine oxide with allylic alcohol, would also undergo a Claisen rearrangement to form 2-oxo-5-alkenyl phosphonate or phosphine oxide 163 [85], The rearrangement is accelerated by the carbanionic nature of the intermediate 162. For the conjugate addition step, the reaction temperature is crucial since the reaction at 0 °C afforded mainly /i,y-unsaturated product whereas a,/8-unsaturated products were formed at 20 °C. 

Denmark and Harmata studied the reaction of 1,2-allenyl sulfones and 2-prope-nols under the catalysis of 5 mol% of sodium alkoxide affording 2-alloxy-2-propenyl sulfone 217, which can be converted to 2-oxo-5-alkenyl sulfone 218 by treatment with 1.5equiv. of KH in HMPA, a carbanion-accelerated Claisen rearrangement [116, 117]. 

The Claisen rearrangement also benefits from a geminal donor to the framework oxygen atom [229]. This forms the basis of many synthetic applications. A newer version of the Claisen rearrangement is the carbanion-accelerated process [230]. It is noted that in all these cases the facilitation is always achieved by alternating polarity accentuation. 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

Acceleration of Claisen rearrangements.2 The Claisen rearrangement of an allyl vinyl ether is markedly accelerated by a stabilized a-sulfonyl carbanion at the 2-position. Thus 1 and 2 rearrange to the y,d-unsaturated ketone 3 in the presence of potassium hydride and 18-crown-6 at moderate temperatures. Rates can be further enhanced by addition of HMPT. Substitution of methyl groups on either the allyl or vinyl units does not affect the regioselectivity but can accelerate the rate of rearrangement. 

Sulfone stabilized carbanions attached at C-2 substantially accelerate the Claisen rearrangement (Scheme 22) these species may be generated from either regioisomeric precursors [142]. These processes take place with high levels of internal asymmetric induction [ 143], and the scope of the process is broad and it has been extensively studied. This acceleration was also noted for the related sulfinyl carbanions, albeit with low yields and in the case of sulfilimines no internal asymmetric induction was observed [144]. 

A high degree of asymmetric induction has been realized in the carbanion-accelerated Claisen rearrangement of phosphorus-stabilized anions. Treatment of 1,3,2-oxazaphosphorinane (166) with freshly prepared lithium dimsylate led to a 95 5 ratio of a-methyl ketones (167) and (168) (Scheme 33). Li coordination combined with steric interactions provide the necessary control elements for stabilization of the highly organized allyl anion conformation (169). 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

The adducts of the reaction of allyl alcohols with allenic sulfones are especially interesting as they allow the carbanion-accelerated Claisen rearrangement to take place. By deprotonation, or directly by addition of an allyl alcoholate anion, a system is generated, which rearranges much more easily than the uncharged system and with high diastereoselectivity (Scheme 62). 

The thio-Claisen rearrangement has its special value when the specific reactivity of a sulfur function, e.g. its carbanion-stabilizing effect or the high nucleophilicity of S, can be utilized, as in syntheses of 7-keto aldehydes (Scheme 72) or thioamides (Scheme 73). ... 

Based on this observation Denmark and coworkers developed a carbanion -accelerated Claisen rearrangement with X = CHS02Aryl K+ 164). While the C6H5S02CH2-substituted vinyl-allyl-ether 182 does not rearrange to give 185 when kept at 50 °C in HMPA 167) for 3.5 h, rearrangement occurs under the same conditions in the presence of potassium hydride. Undoubtedly, with potassium hydride the... 

The carbanion -accelerated Claisen rearrangement is also a viable reaction for the creation of vicinal quaternary centers, as shown, e.g., by the rearrangement of 193 to 194 164 c). A similar carbanion -accelerated Claisen rearrangement of 197 could... 

Two other examples of carbanion -accelerated rearrangements have been described in the literature. The first one leads from the anion of the 60-allylic guanine 211 in two consecutive [3.3] sigmatropic shifts (a combined Claisen-Cope rearrangement) via 212 and 213 to the 8-allylic guanine 214 173). 

Denmark, S.E., and Marlin, J.E., Carbanion-accelerated Claisen rearrangements. Part 7. Phosphine oxide and phosphonate anion stabilizing groups, J. Org. Chem., 56, 1003, 1991. 

The nucleophilicity of sulfur and its ability to stabilize a-carbanions provide sulfur compounds with unique opportunities for sigmatropic processes consecutive rearrangements are no exception. The formation of salt (140) via Sn2 alkylation of ( )-2-butenyl bromide (139) followed by deprotonation leads to the intermediate allyl vinyl ether (141) which, under the conditions of the deprotonation, undergoes a thio-Claisen rearrangement to afford thioamide (143 Scheme 10). Thermolysis of (143) at elevated temperature affords the Cope product (142) in addition to some of its deconjugated isomer. Several unique characteristics of the thio-Claisen sequence should be noted first, the heteroatom-allyl bond is made in the alkylation step, this connection teing not notrtudly practised in the parent Claisen reaction ... 

Table 17. Claisen Rearrangements of Arylsulfonyl-Stabili/.ed Carbanions 04...

Carbanion-Accclerated Claisen Rearrangement in HMPA/THF General Procedure104 ... 

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