Auxiliary terpene-derived

Excellent diastereomeric ratios were achieved with terpene-derived auxiliaries. The pentacarbonyl[(-)-menthyloxycarbene]chromium complex 39 reacted with the sterically hindered 3,3-dimethylbut-l-yne to give tricarbonyl chromium naphthohydroquinone complex 40 in 81% de as the major diastereomer which was also characterised by X-ray analysis [41] (Scheme 25). Surprisingly, the application of other even more sterically demanding terpene auxiliaries or a variation of the alkyne did not improve the diastereomeric ratio [42]. 

As oxidation also converts the original chiral terpene-derived group to an alcohol, it is not directly reusable as a chiral auxiliary. Although this is not a problem with inexpensive materials, the overall efficiency of generation of enantiomerically pure product is improved by procedures that can regenerate the original terpene. This can be done by heating the dialkylborane intermediate with acetaldehyde. The a-pinene is released and a diethoxyborane is produced.204... 

Terpene derived chiral auxiliaries have been employed14, with the best results for the preparation of (,S )-2-mcthyloctanal being 60% yield and 75% ee (Table 5). 

Many chiral auxiliaries are derived from 1,2-amino alcohols.7 These include oxazolidinones (l),7-9 oxazolines (2),10 11 bis-oxazolines (3),1213 oxazinones (4),14 and oxazaborolidines (5).15-17 Even the 1,2-amino alcohol itself can be used as a chiral auxiliary.18-22 Other chiral auxiliaries examples include camphorsultams (6),23 piperazinediones (7),24 SAMP [(S)-l-amino-2-methoxy-methylpyrrolidine] (8) and RAMP (ent-8),25 chiral boranes such as isopinocampheylborane (9),26 and tartaric acid esters (10). For examples of terpenes as chiral auxiliaries, see Chapter 5. Some of these auxiliaries have been used as ligands in reagents (e.g., Chapters 17 and 24), such as 3 and 5, whereas others have only been used at laboratory scale (e.g., 6 and 7). It should be noted that some auxiliaries may be used to synthesize starting materials, such as an unnatural amino acid, for a drug synthesis, and these may not have been reported in the primary literature. 

Glucose,123 and terpene derived ketones,124 have been used as chiral auxiliaries for the formation of new stereogenic centres by a similar method 123... 

In a more recent study, Koizumi et al. employed terpene derivatives as chiral auxiliaries attached to thioaldehydes [405], but these heterodienophiles gave only moderate diastereoselectivities in reactions with cyclopentadiene. Mazzan-ti et al. have investigated the hetero Diels-Alder reaction of thioketones bearing an asymmetric silicon atom directly attached to the thiocarbonyl moiety which induced diastereoselectivities up to 50% de [406]. 

The cix dihydroxylation of 2-methyl-2-butenoic acid esters of terpenic derivatives takes place with diastereomeric ratios of up to 84 16. In all the examples shown, the stoichiometric osmylation occurs with a better selectivity than the catalyzed version. Reductive treatment of the protected diols allows cleavage of the auxiliary and its quantitative recovery2. 

The use of the terpene-derived auxiliaries has been extended to the reaction of chiral 2-butenylboranes with achiral aldehydes [125d,h]. The relative diastereo- ... 

Terpene derivatives are also used as chiral auxiliaries, as in example 10.31.65... 

Chiral alkoxy-l,3-cyclohexadienes 1 add to 1,4-naphthoquinone (2) yielding 3 with moderate to very high diastereomcric ratios. The best results (d.r. 97.5 2.5) are achieved for dienes le and lf(l,2 5,6 -di-O-isopropylidene-a-D-glucopyranoside as an auxiliary). Diene Id (2.3,4,6-tetra-0-methyl-/(-D-glucopyranoside as auxiliary) gives a d.r. of only 58.5 41.5. Terpene derivatives as auxiliary alcohols do not work much better d.r. 63 27, 53 47, 64 36 are obtained for la [(-)-borneol], lb [( — )-menthol] and lc [(—)isopinocampheol], respectively18. 

Dysidiolide is a terpene of current interest in medicinal chemistry. Its structure invites creative approaches. The first synthesis by the Corey group [21] (Scheme 11.16) starts from a readily available chiral building block with one stereogenic center. The striking fact is that this stereogenic center appears nowhere in the target structure. It serves as an auxiliary to derive the other stereogenic centers and ultimately it had to be removed in an impressive way. 

Chiral Dialkylboranes. Several allylic boranes have been developed as chiral auxiliary reagents (Fig. 5). The introduction of terpene-based reagents such as 12 and 64-68 has been pioneered by H.C. Brown, and the most popular class remains the bis(isopinocampheyl) derivatives (structures 12, 64-66). A wide variety of substituted analogs have been reported, including the popular crotylboranes but also a number of other reagents bearing heteroatom-... 

Mur 207), has received renewed interest in recent years. A fine review covering the intermolecular asymmetric Diels-Alder reaction was compiled by Mori 208>. In this article the use of terpenes and carbohydrates as chiral auxiliaries is discussed no amino acid derivatives are mentioned in this context. A chiral a-hydroxycarboxylic acid derivative was also used to achieve an asymmetric Diels-Alder reaction 209). High asymmetric induction could be detected in the intramolecular Diels-Alder reaction of chiral molecules. 

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