Ynone substrates

The total synthesis of pyrrolidinol alkaloid, (+)-preussin was achieved in five efficient transformations from commercially available fert-Boc-(S)-phenylalanine in the laboratory of S.M. Hecht. The key step involved the Hg "-mediated 5-endo-dig cyclization of ynone substrate affording the desired pyrrolidinone which, in two more steps, was converted into the natural product. 

The cyclic peroxide natural product (+)-chondrillin was prepared by P.H. Dussault and co-workers using a singlet oxygenation/radicai rearrangement sequence as the key step. The first stereocenter was introduced via the Midland reduction of an ynone substrate. 

TMM cycloadditions to cyclic and conjugated ketones have also been reported (Scheme 2.22) [31]. The steric nature of the substrate does play a critical role in determining product formation. Thus the cyclic ketone (73) produced 55% yield of the tetrahydrofuran, but no cycloadduct could be obtained from the cyclic ketone (74). The enone (75) gave only carbonyl cycloaddition, whereas enone (76) yielded only olefin adduct. Interestingly, both modes of cycloaddition were observed with the enone (77). The ynone (78) also cycloadds exclusively at the carbonyl function [34]. 

In a photometric assay NADP(H)-dependent LBADH (see above) [9] and NAD(H) -dependent Candida parapsilosis carbonyl reductase (CPCR) [40] were identified as suitable catalysts accepting a broad range of ynones as substrates. Both enzymes catalyze the reduction of various aryl alkynones 21 with high enantioselectivity and efficiency (Scheme 2.2.7.13) [41]. 

Cyclization ofsilyl enol ethers of -acetylenic ketones or aldehydes. Reaction of these derivatives of ynones or -als with HgCl2 (1.1 equiv) and hexamethyldisi-lazane (0.2 equiv.) as an acid scavenger in CH2C12 at 30° followed by acidification with aqueous HC1 and Nal (2 equiv. each) results in cyclic 0,y-enones. Thermal cyclization of these substrates requires high temperatures, which lead to decomposition and rearrangements.1... 

An expedient method for the preparation of isochromene carboxylates (203) has been developed, which relies on the regioselective 1,6-addition of various nucleophiles, such as Grignard reagents, alkoxides, and cyanide, to benzopyranylidenetungsten(O) complexes (201), followed by iodine oxidation of the addition intermediates (202)254 DFT calculations have been carried out to rationalize the unusual switch in stereoselectivity, where ynone and ynoate substrates exhibit opposite stereochemical preferences in the stannylcupration.255... 

Although CrCl2 and CrS04 are the two low-valent chromiutn(II) salts typically used5 to reduce ynones to trans enones, both reagents failed to give satisfactory yields of product when applied to 7. However, when [Cr(OAc)2 H20]2 was employed for this reduction (Scheme 7.4), a 60% yield of product was obtained. Double O-desilylation was next performed to access diol 6, the substrate needed for the Sharpless AD reaction.3... 

Scheme11.11 Remote steric effect of substrate and 6-substituent on enantioselection in the 2-catalyzed reduction of an a,P-ynone.

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