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5.5 Conclusion
This chapter has dealt with the use of chiral auxiliaries, chiral controllers, and chiral reagents
in asymmetric versions of the PKR. The chiral auxiliary strategy has played a key role in the
applicability of this powerful transition-metal mediated cycloaddition, largely overlooked
in the decade following its discovery, to the enantioselective total synthesis of natural
products; in this aspect, it is only surpassed by approaches based on the use of “chiral-pool”
derived compounds (now including both natural and purely synthetic molecules) as starting
materials.
62
Many types of chiral auxiliaries have been explored both for intramolecular
and intramolecular PKRs in the past three decades. The Barcelona-Grenoble approach,
making use of chiral alcohols attached either to the alkyne or to the alkene components,
has been shown to be applicable to both versions of the reaction, and has given rise
to several total or formal syntheses of relatively complex natural products. Chiral vinyl
sulfoxides, applied as removable chiral controllers in the PKR by Carretero's group, have
also given rise to highly useful protocols. Although it is true that recent approaches to the
development of PK or of PK-type reactions have been mainly focused on the chemically
more efficient use of chiral metal complexes, ideally in catalytic or at least substoichiometric
fashion, it must be borne in mind that chiral auxiliaries can still provide very useful
approaches for the preparation of certain types of enantiomerically pure PK cycloadducts,
especially in the intermolecular version. Thus, chiral
N
-(2-alkynoyl)sultams have given
rise to the highest levels of stereocontrol ever achieved in intermolecular PKRs. From a
practical point of view, moreover, chiral auxiliaries, both in the PKR as well as in other
widely used asymmetric carbon-carbon bond-forming reactions, exhibit a certain number
of advantages: a) several of them (
trans
-2-phenylcyclohexanol, 4-phenyl-1,3-oxazolidin-
2-one, bornane-10,2-sultam) are commercially available in both enantiomeric forms; b)
diastereomericmixtures of products are inmany instances easily separable by crystallization
or by chromatography, affording completely enantiopure compounds (getting enantiopure
compounds from enantiomerically enriched mixtures is not always feasible); c) they can be
recovered from the adduct and reused, while with scarce exceptions chiral phosphine-based
ligands are not recoverable from PK reaction mixtures; and d) the stereochemical outcome
of the reaction can often be reliably predicted from simple transition state working models.
Acknowledgements
Financial support from MICINN (Project AYA2009-13920-C02-02) is gratefully acknowl-
edged.
References
[1] C. Exon and P. Magnus, Stereoselectivity of intramolecular dicobalt octacarbonyl
alkene-alkyne cyclizations: short synthesis of
dl
-coriolin,
J. Am. Chem. Soc.
105
,
2477 (1983).
[2] I. U. Khand, G. R. Knox, P. L. Pauson, W. E. Watts, and M. I. Foreman, Organocobalt
complexes. Part
II. Reaction of acetylenehexacarbonyl dicobalt complexes
