Camphor-derived auxiliaries

It is also possible to carry out a substrate-controlled reaction with aldehydes in an asymmetric way by starting with an acetylene bearing an optically active ester group, as shown in Eq. 9.8 [22]. The titanium—acetylene complexes derived from silyl propiolates having a camphor-derived auxiliary react with aldehydes with excellent diastereoselectivity. The reaction thus offers a convenient entry to optically active Baylis—Hillman-type allyl alcohols bearing a substituent (3 to the acrylate group, which have hitherto proved difficult to prepare by the Baylis—Hillman reaction itself. 

Scheme 4.71 Camphor-derived auxiliary for the asymmetric synthesis of chiral allene ether 280.

The amino alcohol-catalyzed enantioselective addition of dialkylzincs to aldehydes, detailed in Chapter 5 (27), is accomplished with polymer catalysts containing DAIB, a camphor-derived auxiliary, and other chiral amino alcohols (28). Reactions that involve matrix isolation of the catalyst not only result in operational simplicity but also greatly facilitate understanding of the reaction mechanism. In solution, the catalytic chiral alkylzinc alkoxide derived from a dialkylzinc and DAIB exists primarily as dimer (27) however, when immobilized, its monomeric structure can be maintained. 

A new camphor-derived auxiliary was developed by Dixon and coworkers as a stereodirecting group for highly diastereoselective alkylations of an attached glycinamide residue... 

Related Reagents. Prolinol ephedrine oxazolidinones cam-phorsultams camphor-derived auxiliaries and oxazolines. 

What role does the camphor-derived auxiliary play in this reaction ... 

This is a Diels-Alder reaction in which 25 as the dienophile and 26 as the diene form a new cyclohexene ring. In terms of the electron demand this is a normal Diels-Alder reaction with an electron-rich diene 26 and an electron-poor dienophile 25. The use of a chiral camphor-derived auxiliary means that only one diastereomer is obtained in 70 % yield. The reaction proceeds via the endo transition state 38 with the auxiliary blocking one side of the dienophile. 

Scheme 6.42. Camphor-derived auxiliaries for asymmetric Diels-Alder cycloadditions. (a,b) [170]. (cj [171]. The auxiliary illustrated in (a) is the enantiomer of that reported in ref. [170].

Table 5.5 32.49. and used the auxiliary derived Irom camphor quinone to synthesi/.e the key hy-droxyben/.ylisoquinoline intermediates 19. 20. and 2.5 shown in Scheme 5.12 ].521. The absolute configuration of the new stereocenters of the addition products from ihese two auxiliaries (derived lrum. V-valine and l-/ -eaniphorqiiinonc oximei are opposite. In the schemes and accompany ing discussion below, the camphor-derived auxiliary is illustrated (Scheme 5.12), but die rest of the synthesis of all the alkaloids except eorlumine was actually executed on ihe enantiomer of that draw n. because it was done with the producl of addition using die valine-derived auxiliary. The references in die discussion refer to the relevant papers for each step. 

Fig. 5.4. Probable conformation of the magnesiated lelrahydroisoquinolyl oxazolinc. based on analogy to the X-ray crystal structure of a magnesiated tetrahyrdoisoquinoline pivalanride 143. The aldehyde probably coordinatc,s to one of the ligand sites cis to the isoquinolyl carbon prior to reaction, (a) Conformation of isopropyl in 5-unsuhstitutcd auxiliary (b) Steric crowding produced by rotation of isopropyl in the 5..5-diinclhyl derivative (c) Similar crowding in a camphor-derived auxiliary (enantiomer of that drawn in Table 5, 5. entries 12 and L5).

Sato and co-workers have developed an elegant titanium alkoxide promoted MBH reaction between enantiopure acetylenic esters 262-264 (Figure 2.16) and aldehydes. A new chiral dimetallic species, the acetylenic ester titanium alkoxide complex with a camphor-derived auxiliary, enabled the preparation of p-trimethylsilylated MBH adducts 265 with high diastereoselectivity (Scheme 2.150). ... 

Scheme 4.7 Glycine alkylation through camphor-derived auxiliary 35.

Alkylation Alkylation of ACC hydrazones proceeds with both excellent stereo- and regiochemical control and in excellent yield. As mentioned, camphor-derived auxiliary 54 and phenyl alanine-derived auxiliary 55 have proven to be the most versatile. Although the initial report on ACCs gave an er of 96 4 for ACC 54 and of 76 24 for ACC 55 in the allylation of 3-pentanone, subsequent work has revealed that in fact ACC 54 produces an er of >99 land 55 an er of 95 5 (Table 7.1). ... 

Helmchen [67] and Oppolzer [68] investigated and documented the use of camphor-derived auxiliaries in Mukaiyama aldol reactions. Silyl ketene acetals 106 and 108 participate in diastereoselective additions to aldehydes in the presence of TiCl4, affording adducts with up to 99 1 diastereoselectivity (Equations 7 and 8). 

Denmark advanced a strategy that involves tandem cycloaddition sequences with nitronates for the asymmetric synthesis of alkaloids [73, 74). A camphor-derived auxiliary permits the preparation of chiral enol ethers (cf. 68) as the reacting partners. A noteworthy example of the complex structures that could be generated by use of 68 is illustrated in Scheme 18.15. A hetero-Diels-Alder reaction between 68 and nitronate 67 generated 69 as a 96 4 mixture of endo/exo diastereomers. The adduct then participated in an intramolecular dipolar cycloaddition at elevated temperatures to yield cycloadduct 70 as a single diastereomer (90%). The tricyclic target 72 was obtained in 88 % yield after reductive removal of the chiral auxiliary and lactam formation [74]. 

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