Carbanion-accelerated Claisen rearrangements

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 A newer version of the Claisen rearrangement is the carbanion-accelerated process [230].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. 

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). 

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. 

Arylsulfonylmethyl groups101-104,516 in the 2-position of the pericyclic system and related phosphorus compounds517 have been intensively investigated in carbanion-accelerated Claisen-type rearrangements (cf. Section 1.6.3.1.1.1. p3304). 

It is possible to enhance the rate of a Claisen rearrangement, especially in the enolate Claisen reaction. Denmark et al. showed that other carbanionic centers accelerate the Claisen rearrangement (as in Table 11.23).467 Generation of the anion of sulfone 631 (sec. 8.6.A) with various bases led to acceleration of the reaction relative to the thermal reaction of 631 and also influenced the syn/anti ratio (632/633). In general, a donor group at the allyl position accelerates the rate and the presence of an amino stabilizing group increases the rate even more. 

Denmark has developed the carbanion accelerated Claisen rearrangement [15, 72-78]. It is known that the nature of the transition state of Claisen rearrangement is dependent on the substituents present [79]. The effects of substituents have been studied in detail by Carpenter [80]. At positions Cl, C2, and C4 both donor and acceptor substituents accelerate the reaction with respect to hydrogen (Eq. 3.1.58). Furthermore, the synthetic versatility of the Claisen rearrangement primarily resides in the variety of the substituents X that determine the carbonyl derivative... 

Tab. 3.1.7 Carbanion-accelerated and thermal Claisen rearrangements of the phosphonates (Eq.3.1.64).

Denmark has also investigated the carbanion accelerated Claisen rearrangement of allyl vinyl ethers with cydic phosphonamides as carbanion-stabihzing groups [78], because phosphonamide allyl anion is well established and has potential for chiral modification. 

A phosphorus-stabilized, carbanion-accelerated Claisen rearrangement has been reported to be site- and stereo-selective with the asymmetric induction dependent on the auxiliary and the metal counterion involved (Scheme 25) ... 

Claisen-Umlagerung (Rearrangement) assymetr. E21d, 3534 (von Allyl-vinyl-ether) two-directional E21d, 3399 Carbanion-indiziert (accelerated) E21d, 3440... 

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