Shi epoxidation

In the synthesis of the squalenoid glabrescol (72 originally attributed structure), containing five adjacent (all cis) THF rings, the necessary precursor of the polyepoxide cascade, the pentaepoxide 71, was achieved by epoxidation of each of the trisubstituted double bonds of the known (R)-2,3-dihydroxy-2,3-dihydrosqualene (70) by the Shi epoxidation approach (Scheme 8.18) [34]. Treatment of 71 with CSA at 0 °C and subsequent purification by column chromatography provided the pure polycyclic ether 72 by a cascade process reasonably initiated by the free secondary alcohol functionality [35a]. 

Shi epoxidation 283 Shibasald 234, 236, 242 Shikimate pathway 407 [3,3]-sigmatropic rearrangement 51 silicon-lithium exchange 157 single-carbon homologation... 

We have put forward (J. Am. Client. Soc. 2004, /26, 13900) an alternative approach to the enantioselective construction of cyclic quaternary centers. Addition of phenylacetylene to cyclopentanone followed by dehydration and Shi epoxidation gave the epoxide 10. Opening of the epoxide with allylmagnesium chloride proceeded with inversion, to give II. The alcohol 11 can also be carried on to bicyclic products, exemplified by the sulfone 12. 

It should be mentioned here that in addition to the Julia-Colonna epoxidation, the Shi epoxidation is also attracting commercial interest. In a recent presentation DSM reported current activity on the application of the Shi technology on a commercial scale [43],... 

The Shi epoxidation has found several applications in total synthesis [15]. Particularly attractive are examples in which it has been used to establish the stereochemistry of polyepoxides which can undergo cascade cyclizations to polyether products, mimicking possible biosynthetic pathways. An example is the construction of the tetahydrofuran rings of the natural product glabrescol via highly stereoselective formation of the tetraepoxide 10 from the polyene 9 (Scheme 12.6) [22]. 

Scheme 12.6 Shi epoxidation in the total synthesis of glabrescol (right).

Scheme 12.7 Shi epoxidation using hydrogen peroxide as co-oxidant.

Mechanism of Shi epoxidation was probed for synthesis of (+)-(R,R) epoxide 20 in the reaction of frans-2-methylstyrene 18 with peroxymonosulphate (Oxone) in the presence of catalyst 19, chiral ketone derived from fructose (Scheme 5).74... 

Figure 9 Experimental and predicted (in brackets), 3C KIEs for Shi epoxidation of trans-2-methylstyrene 18.

Ager D, Anderson K, Oblinger E, Shi Y, VanderRoest J (2007) An epoxida-tion approach to a chiral lactone application of the Shi-epoxidation. Qrg Process Res Dev 11 44... 

In the Shi epoxidation, an oxone (potassium persulfate, KOSO2OOH) in the presence of a fructose-derived catalyst, 7.57, generates epoxides with high enantiomeric excess oxone is best used to oxidize aldehydes to carboxylic acids in the presence of DMF. 

The synthesis of cryptophycin 52 was accomplished by E.D. Moher et al. using the Shi epoxidation as the key step to install the epoxide moiety diastereoselectively. In the previous syntheses of this moiecuie, the epoxide moiety was always introduced in the last step, using common oxidants such as mCPBA or DMD, and with poor diastereoselectivity. Interestingly, the usual alkene precursor was a very poor substrate for the Shi epoxidation, so an earlier intermediate was subjected to the epoxidation conditions in which the pH was very carefully controlled. The desired epoxide was obtained as a 6.5 1 mixture of diastereomers. 

The Shi epoxidation was the key step in E.J. Corey s total synthesis of the chiral C2-symmetric pentacyclic... 

Besides the secondary amine-catalyzed oxygenation reactions (see Sects. 2.3.1. and 3.2.5.) and phase-transfer catalyzed epoxidations (Chap. 6.) already mentioned, asymmetric epoxidation reactions using the method developed by Shi et al. (530) have found to be highly useful in complex total syntheses (531-535). The Shi epoxidation employs the fructose-derived ketone 629 as an easily available namral... 

Scheme 131 Asymmetric Shi epoxidations in the total synthesis of (+)-aurilol (633)...

Besides the Shi epoxidation, which has also proven its potential in a series of other complex syntheses (532, 534, 542), the Julia-Colonna asynunetric epoxidation (543-545) using polyamino acid catalysts also has been found to be a versatile method in total synthesis (546-548). In 1998, the group of Roberts reported a... 

Hoard DW, Moher ED, Martinelli MJ, Norman BH (2002) Synthesis of Cryptophycin 52 Using the Shi Epoxidation. Org Lett 4 1813... 

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