Contiguous quaternary centers

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

While the yields are generally good for the cyclization of diimines derived from aldehydes, the process does not work satisfactorily using diketoimines such as 20. This is not too surprising, given the need to form two contiguous quaternary centers in 21. 

Casey and coworicers have shown that ketone etiolates add efficiently to a,3-unsaturated vinyl carbene complexes (164), irrespective of 3,3-disubstitution on the complex or high substitution on the enol-ate 133 thus, contiguous 3 and y quaternary centers are easily assembled. When coupled with the ease of release of the carbene ligand from the complexes by either oxidation to the ester functionality1331 or elimination to the corresponding enol ether,133 the vinyl carbene complexes are synthetic equivalents for a,3-unsaturated esters or a,3-unsaturated aldehydes, respectively (Scheme 63). 

By virtue of its seven contiguous stereogenic centers, including two quaternary centers, and the presence of very sensitive functionalities such as the exocyclic epoxide and the acetal unit, clerodin 1 84 (Scheme 12.14) represents perhaps one of the most complex diterpenoids isolated. 

Several factors contribute to the versatility of the ester enolate Claisen rearrangement. Among these are the ability to use a stoichiometric combination of the alcohol and the acid components, the relatively low temperature - of the pericyclic process that allows for the assembly of complex, highly functionalized structures, and the transformation of a carbon-oxygen into a carbon-carbon bond that lends itself easily to the assembly of contiguous quaternary centers. - ... 

Gilbert, J. C., Kelly, T. A. Diastereoselective formation of contiguous quaternary centers. The modified Carroll rearrangement. Tetrahedron 1988,44, 7587-7600. 

Radical cyclization of 4-[(bromomethyl)dimethylsiloxy]-2-methyl-l-undecen-5-yne in the presence of acrylonitrile leads stereoselectively by a radical cascade to the diquinane system71. This one-pot reaction allows the consecutive formation of four C-C bonds with two contiguous quaternary centers, and controls the stereoselective construction of four stereogenic centers. 

Scheme 5.43 illustrates three applications of this methodology to total synthesis. The first exeunple is taken from Posner s synthesis of estrone and estradiol [211], the second from Posner s synthesis of methyl jasmonate [212], and the third from Holton s synthesis of aphidicolin [213]. The latter is particularly noteworthy in that two contiguous quaternary centers are created in the asymmetric addition with excellent selectivity. In the estrone synthesis, the chirality sense of the product is consistent with the nonchelate model, but the other two examples adhere to a chelate model. Note that the difference is the degree of substitution at the a-position of the enolate. 

In the case of 1,1,2,2-tetramethylenecyclobutane made optically active by virtue of labeling frani-methyls with deuterium, pyrolytic retro 2 + 2 cycloaddition is much faster than either double or single rotation. This must represent the difficulty of reclosure of any biradical to generate two contiguous quaternary centers relative to cleavage. 

Figure 13.14 Generation of products possessing contiguous quaternary centers.

The skeleton of the sesquiterpenes thapsene 140 and 141 contains three contiguous quaternary centers [33]. The synthesis of two biogenetical precursors of these terpenes started with cyclogeraniol 143. Orthoester rearrangement afforded ester 144. As in several other syntheses, the third quaternary center resulted from diazoketone cyclopropane insertion affording in this synthesis compound 146 (Scheme 6.21). 

The diastereoselective construction of polycyclic structures such as linear triquinanes has been explored by the Malaciia group from acychc or macrocyclic precursors. Based on an acyclic (bromomethyl)dimethylsilyl precursor, the outcome of the sequence leading to the triquinane is remarkable five new C-C bonds, two contiguous quaternary centers, and four new stereogenic centers can be formed with almost complete control (eq 17). 3... 

Phosphine-Catalyzed Reactions Phosphine-catalyzed [3+2] dipolar cycloaddition has been applied in an intramolecular manner, whereby three contiguous stereogenic centers, including a quaternary center, are created in a single operation (Scheme 6.27). It may be noted that the intramolecular cycloaddition is stereospecific. When the E-isomer is used as the starting material, the quaternary center formed possesses the stereochemistry consistent with the structural features of hirsutene [31]. 

One of the problems encountered in the synthesis of polycyclic compounds is the stereoselective formation of quaternary carbon centers. Barriault and coworkers reported the development of domino oxy-Cope/Claisen/ene reaction of divinyl cyclohexanol 130 as an efficient method for the assembly of decalin system possessing contiguous quaternary centers such as 133 (Scheme 8.21) [54]. Heating of alcohol... 

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