Stereocenter quaternary

The high catalytic activity also enabled aza-Claisen rearrangements to form Al-substituted quaternary stereocenters (Fig. 26) [71]. The catalyst does not need to distinguish between differently sized substituents on the double bond of 49 (e.g., R = CDa, R = CHs, ee = 96%), indicating that coordination of the olefin is the stereoselectivity predetermining step. The imidate-N-atom subsequently attacks intermediate 47-1 from the face remote to the Pd-center totally resulting in a... 

Fig. 26 Asymmetric aza-Claisen rearrangement of trifluoroacetimidates 49 generating iV-substi-tuted quaternary stereocenters...

Alternative catalytic asymmetric acylation reactions studied prochiral silyl imi-noketenes 89 [110] (Fig. 44, top) and silyl ketene acetals 90 [111, 112] (Fig. 44, middle), leading to the formation of quaternary stereocenters. Furthermore, the... 

Fischer DF, Xin ZQ, Peters R (2007) Asymmetric formation of allylic amines with N-substimted quaternary stereocenters by Pd -catalyzed Aza-Claisen rearrangements. Angew Chem Int Ed 46 7704-7707... 

Jautze S, Peters R (2008) Enantioselective bimetallic catalysis of Michael additions forming quaternary stereocenters. Angew Chem Int Ed 47 9284-9288... 

Mermerian AH, Fu GC (2005) Catalytic enantioselective construction of all-carbon quaternary stereocenters synthesis and mechanistic studies of the C-acylation of silyl ketene acetals. J Am Chem Soc 127 5604—5607... 

Ruble JC, Fu GC (1998) Enantioselective construction of quaternary stereocenters rearrangements of 0-acylated azlactones catalyzed by a planar-chiral derivative of 4-(pyrrolidino) pyridine. J Am Chem Soc 120 11532-11533... 

Hills ID, Fu GC (2003) Catalytic enantioselective synthesis of oxindoles and benzofuranones that bear a quaternary stereocenter. Angew Chem Int Ed 42 3921-3924... 

Quaternary Stereocenters-Challenges and Solutions for Organic Synthesis, J. Christolfers, A. Baro, ed., Wiley-VCH, Weinheim, 2005. 

An jV-heterocyclic carbene 110 catalyzed the rearrangement of the 0-acyl carbonates 109 into their corresponding C-acylated isomers 111, generating a C-C bond and a quaternary stereocenter with high efficiency <06OL3785> The same reaction can be performed enantioselectively using TADMAP 112 <06JA925>. 

The previous section discussed chelation enforced intra-annular chirality transfer in the asymmetric synthesis of substituted carbonyl compounds. These compounds can be used as building blocks in the asymmetric synthesis of important chiral ligands or biologically active natural compounds. Asymmetric synthesis of chiral quaternary carbon centers has been of significant interest because several types of natural products with bioactivity possess a quaternary stereocenter, so the synthesis of such compounds raises the challenge of enantiomer construction. This applies especially to the asymmetric synthesis of amino group-substituted carboxylic acids with quaternary chiral centers. 

FORMATION OF QUATERNARY STEREOCENTERS THROUGH DIELS-ALDER REACTIONS... 

Besides the methods discussed in Chapter 2, some quaternary stereocenters can also be conveniently constructed through the enantioselective Diels-Alder reaction of the 2-substituted acroleins 75 and 128-130. 

Formation of Quaternary Stereocenters Through Diels-Alder... 

Scheme 6.41. Stereoselective construction of a quaternary stereocenter by allylic substitution of mesylate 195 with a boron trifluoride-modified cyano-Gilman cuprate reagent.

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

As shown in previous sections, NHCs promote acyl transfer in transesterification reactions. In a similar manner, O C acyl transfer can be achieved with substrates such as 351 in the presence of 0.9 mol% of triazolium pre-catalyst 353 and KHMDS (Scheme 53). Moderate yields are obtained by varying substitution of the oxazole from R = Me, Ph, t-Bu, and t-Pr [171], Deprotonation of the triazolium salt followed by nucleophilic addition to the carbonate moiety of the oxazole results in enolate intermediate LXXXIII and activated carboxylate LXXXIV. Enolate addition and regeneration of the active catalyst provides quaternary stereocenters 352. 

The efficiency with which modified Cinchona alkaloids catalyze conjugate additions of a-substituted a-cyanoacetates highlights the nitrile group s stereoselective role with the catalyst. Deng et al. [60] utilized this observation to develop a one-step construction of chiral acyclic adducts that have non-adjacent, 1,3-tertiary-quatemary stereocenters. Based on their mechanistic studies and proposed transition state model, the bifimctional nature of the quinoline C(6 )-OH Cinchona alkaloids could induce a tandem conjugate addition-protonation reaction to create the tertiary and quaternary stereocenters in an enantioselective and diastereoselective manner (Scheme 18). 

If the 3-position is a quaternary stereocenter, then Rh(I)/Tol-BINAP is the catalyst of choice for the hydroacylation process. With this catalyst, both kinetic resolutions (Eq. 20) and desymmetrization reactions (Eq. 21) may be accomplished. 

If the 3-position is a tertiary, rather than a quaternary, stereocenter, Rh(I)/Tol-BINAP effects an intriguing parallel kinetic resolution - thus, one enantiomer of the substrate selectively undergoes hydroacylation to generate a cyclobutanone, while the other enantiomer is transformed into a cyclopentanone (Eq. 22) [24]. This observation is quite interesting, given the limited number of examples of parallel kinetic resolutions, particularly catalytic processes that involve carbon-carbon bond formation, and catalytic methods for the construction of cyclobutanones. 

It is known that 5-acyloxyoxazoles 132 rearrange to 4-acyl-5(4/l/)-oxazolones 133 in the presence of 4-(dimethylamino)pyridme or 4-(pyrrohdino)pyridine. Recently, an asymmetric variant of this nucleophUe-catalyzed rearrangement that employs a chiral derivative of 4-(pyrrolidino)pyridine has been described. This procedure allows the construction of quaternary stereocenters with high levels of enantioselectivity (Scheme 7.38). Representative examples of saturated 5(4//)-oxazolones prepared via sigmatropic rearrangements are shown in Table 7.16 (Fig. 7.18). 

As is depicted in Scheme 1.2.29, the epoxide 128 was synthesized starting from 2,2-dimethyl-l,3-dioxan-5-one RAMP hydrazone (R)-96, which was double-alkylated with methyl iodide at a- and a -positions leading to the trons-dimethylated hydrazone 131 in 79% yield over two steps and excellent stereoselectivity (de, ee > 96%) [68]. The quaternary stereocenter bearing the desired tertiary alcohol function was generated using benzyloxymethyl chloride (BOMCl) as the electrophile to trap the lithiated hydrazone 131, providing the a-quaternary hydrazone 132 in very good yield (92%), excellent diastereomeric and enantiomeric excesses (de, ee > 96%) and with the required cis relationship of the methyl substituents. 

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