Of quaternary carbons

Conjugate addition [2] to Midiael acceptors is die most important and usefid reaction in orgatiocopper diemistiy, and die reaction is ofien used as die key step in die syndiesis of numerous natural and unnatural products. Perhaps one of die most efficient methods for die syndiesis of quaternary carbon centers is organo-copper-mediated conjugate addidon to /, / -disubstituted enones. 

The broad-band decoupled C-NMR spectrum of malabarolide-Ai shows signals for all 18 carbon atoms. The DEPT spectrum (0 = 135°) exhibits 14 signals for protonated carbons. It is therefore possible to identify four signals of quaternary carbons, i.e., 8 39.2 (C-9), 74.7 (C-8), 126.0 (C-13), and 171.8 (C-18 carbonyl). The DEPT (0 = 90°)... 

The HMBC spectrum of vasicinone displays long-range heteronuclear shift correlations between the various H/ C nuclei. These correlations are very helpful to determine the C-NMR chemical shifts of quaternary carbons and allow the interlinking of the different substructures obtained. 

Catelani D, A Colombi, C Sorlini, V Treccani (1977) Metabolism of quaternary carbon compounds 2,2-dimethylheptane and tcrt-butylbenzene. Appl Environ Microbiol 34 351-354. 

Kniemeyer O, C Probian, R Rossello-Mora, J Harder (1999) Anaerobic mineralization of quaternary carbon atoms isolation of denitrifying bacteria on dimethylmalonate. Appl Environ Microbiol 65 3319-3324. 

N-Aziridinylimines are valuable substrates for domino radical cydizations since they are able to serve simultaneously as radical acceptors and donors. They allow a versatile and general construction of quaternary carbon centers from carbonyl compounds [33]. By employing this methodology, an elegant and stereoselective synthesis of ( )-modhephene (3-70), one of the rare naturally occurring [3.3.3]propellanes,... 

They have developed direct asymmetric synthesis of quaternary carbon centers via addition-elimination process. The reactions of chiral nitroenamines with zinc enolates of a-substituted-8-lactones afford a,a-disubstituted-6-lactones with a high ee through addition-elimination process, in which (5)-(+)-2-(methoxy methy l)pyrrolidine (SMP) is used as a chiral leaving group (Eq. 4.96).119 Application of this method to other substrates such as a-substituted ketones, esters, and amides has failed to yield high ee. 

Because reductive cleavage of aliphatic nitro compounds with Bu3SnH proceeds via alkyl radicals, nitro compounds are also used as precursors to alkyl radicals. Reactions using nitro compounds may have some advantages over other ones, since aliphatic nitro compounds are available from various sources. For example, the sequence of the Michael additions of nitro compounds provides an excellent method for the construction of quaternary carbon compounds (Eq. 7.79).126 Newkome has used this strategy for the construction of dendritic polymers (Eq. 7.80).127... 

The study of Fuji et al. shows that the addition of lithium enolate 75 to ni-troamine 74 is readily reversible quenching conditions are thus essential for getting a good yield of product 76. An equilibrium mixture of the adducts exists in the reaction mixture, and the elimination of either the prolinol or lactone moiety can take place depending on the workup condition (Scheme 2-34). A feature of this asymmetric synthesis is the direct one pot formation of the enantiomer with a high ee value. One application of this reaction is the asymmetric synthesis of a key intermediate for indole type Aspidosperma and Hun-teria alkaloids.68 Fuji69 has reviewed the asymmetric creation of quaternary carbon atoms. 

As mentioned in Section 2.3, a large number of biologically active natural products contain quaternary carbon atoms, and the addition of carbon nucleophiles to ketones has attracted increasing attention for the construction of quaternary carbon centers. 

For a review of catalytic en-antioselective methods for the synthesis of quaternary carbon stereogenic centers, see a) E. J. Corey, A. Guzman-Perez, Angew. Chem. Int. Ed. 1998, 37, 388-401. For more recent examples, see b) B. M. Trost,... 

Pd-catalyzed Heck reactions are among the most effective methods for the formation of quaternary carbon centers. Considering the significance and the strategic difficulties associated with the synthesis of quaternaiy carbons, particularly in the optically enriched or pure form, it is not a surprise that the development of catalytic asymmetric Heck reactions has held center stage for the past few years. One of the leading labs in this area is that of Shibasaki, who in 1993 reported a concise total synthesis of eptazodne 23 (Scheme 4).141 Thus, treatment of silyl ether 18 with 10 mol% Pd(OAc>2 and 25 mol% (S)-19 leads to the formation of 20 in 90 % yield and 90% ee As illustrated in Scheme 4, once the quaternary carbon center is synthesized efficiently and selectively, the target molecule is accessed in a few steps. 

Since the conversion of 235 to 233 requires only heating, it is possible to synthesise the vinylketenimine complex directly from the vinylketene merely by extending the reaction time sufficiently.69,87,89 Note that 233.j and 233.k were obtained as 1 1 mixtures of diastereoisomers. The subsequent reactivity of the vinylketenimine complexes,87,89,135,143 particularly their utility in the asymmetric synthesis of quaternary carbon centers,143 has also been investigated, but is beyond the scope of this review. 

The intramolecular coupling of enolethers with enolethers, styrenes, alkyl-substituted olefins, allylsilanes, and vinylsilanes was systematically studied by Moeller [69]. Many of these coupling reactions turned out to be compatible with the smooth formation of quaternary carbon atoms (Eq. 11) [70], which were formed diastere-oselectively and led to fused bicyclic ring skeletons having a ds-stereochemistry [71]. The cyclization is compatible with acid-sensitive functional groups as the allylic alkoxy group. Moeller has demonstrated in some cases that these reactions can be run without loss of selectivity and yield in a simple beaker with either a carbon rod or reticulated carbon as anode without potential control and a 6-V lantern battery as power supply [71]. 

The intramolecular coupKng of enolethers with enolethers, styrenes, dienes, alkyl-substituted olefins, allylshanes, and vinylshanes was systematically studied by Moeller [90,198-200]. These couplings allow the smooth formation of quaternary carbon atoms in fused bicycKc rings having a cis stereochemistry (Fig. 43) [201, 202]. 

As illustrated by the examples in Table 2.23, this reaction enables the stereoselective generation of quaternary carbon atoms. The resulting cyclohexadienones can be chemically modified in several different ways, and hence are valuable synthetic intermediates. 

Heteronuclear NOE experiments yield additional, but due to their inherent low sensitivity only sparsely exploited information on molecular structures. They are most useful to unravel structural features in the vicinity of quaternary carbons often behaving as barriers when exposed to standard routine experiments dedicated to evaluate coupling networks. Heteronuclear NOE data - in some sense complementary to the data from heteronuclear long-range couplings - are based on dipolar spin-spin interactions and strongly depend on intemuclear distances. In contrast to the sometimes similar Jch... 

The enantioselective construction of quaternary carbon centers is invariably a challenging goal41. The double alkylation of a nonracemic jS-hydroxy ester is a useful preparative method from a collection of procedures which are used to reach this objective. In Table 3 the results from the preparation of quaternary centers by this method are shown. 

Table 3. a-Alkylation of -Hydroxy Esters the Formation of Quaternary Carbon Centers13,16,42-48... 

Good yields and high to excellent diastereoselectivities have been realized by the dianion alkylation of cyclic /1-hydroxy esters (see Table 5). Because of the cyclic structures these results correspond to the creation of quaternary carbon centers. 

A simple method for estimating enthalpies of vaporization is the CHLP protocol . The quantities and req in equation 1 refer respectively to the number of quaternary carbon atoms and non-quaternary carbon atoms in the compound, and is a value that is characteristic of the functional group bonded to the hydrocarbon parent. 

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