Rearrangement pseudo-Claisen

A potent and selective N-methyl-D-aspartate (NMDA) antagonist, AP5112, was synthesized from 111, which was a pseudo-Claisen [2,3] rearrangement product of 110 (Scheme 4.29) [47]. 

Scheme 4.29 Synthesis of AP5 via a thermal pseudo-Claisen [2,3] rearrangement of 110 to 111.

Pudovik. A.N.. and Aladzheva, I.M., Thermal or pseudo-Claisen rearrangement of allyl and propargyl esters of phosphorous acid, Dokl. Akad. Nauk SSSR, 151, 1110, 1963 Dokl. Chem. (Engl. Transl.), 151, 634, 1963. 

Structure B corresponds to the most stable transition state of the Ireland-Claisen rearrangement of Figure 14.49. In this transition state, the substituent at the allylic stereocenter is in a pseudo-equatorial orientation with respect to the chair-shaped skeleton. This is the same preferred geometry as in the case of the most stable transition state B of the Claisen rearrangement of Figure 14.48. The reason for this preference is as before that is, an allylic substituent that is oriented in this way experiences the smallest possible interaction with the chair skeleton. The obvious similarity of the preferred transition state structures of the Ireland-Claisen rearrangements of Figures 14.49 and 14.48 causes the same trans-selectivity. 

The synthetic utility of this process can be seen by evaluating the examples in Table 2. For example, because the cyclopropane serves as a pseudo alkene and because the [1.5] shift requires a six-memb ed transition state, it relates conceptually to the Cope and Claisen rearrangements. The 7,8-unsaturated carbonyl compounds in Table 2 are those that would otherwise be obtained via Claisen or orthoester Claisen rearrangements, which are normally effected under strongly acidic or strongly basic conditions (Scheme 3). 

Johnson et al found that a tetrasubstituted fluoro alkene could be prepared with modest alkene stereoselectivity by rearrangement of a tertiary acetate ester (Scheme 4.103) [94]. Surprisingly, the major product was the E-isomer. This impUes that the transition state with the nominally larger CH2CH2R group in the pseudo-axial position is favored. The corresponding Johnson-Claisen gave a 1 1 E Z mixture. 

Bienz et al. have reported the Ireland-Claisen rearrangement of 3° allylic esters in which one of the allylic substituents is silicon (Scheme 4.105) [97]. The larger silicon substituent occupies the pseudo-equatorial position of the chair to yield the h-vinylsilane product. Interestingly, the products apparently result from initial C-silylation of the propionate ester followed by a second Z-selective enoUzation of the resulting silyl propionate. The structure of the pentenoic acid product was verified by X-ray crystallographic analysis. 

The major product of the Claisen rearrangement is derived from a preferred chair-like transition state in which the larger substituent occupies the pseudoe-quatorial position. For example, in the Claisen rearrangement of 102, the major product 103 was obtained [74]. 

A full account has been given of Curran s synthesis of pseudo-monic acid involving a Claisen rearrangement of a glycal derivative (see Vol. 18, p.247), together with further examples of such... 

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