Sharpless asymmetric dihydroxylation Synthesis

R,8S)-(+)-Disparlure (12) is the female sex pheromone of the gypsy moth (Lymantria dispar). Advent of Sharpless asymmetric dihydroxylation (AD) allowed several new syntheses of 12 possible. Sharpless synthesized 12 as shown in Scheme 17 [27]. Scheme 18 summarizes Ko s synthesis of 12 employing AD-mix-a [28]. He extended the carbon chain of A by Payne rearrangement followed by alkylation of an alkynide anion with the resulting epoxide to give B. Keinan developed another AD-based synthesis of 12 as shown in Scheme 19 [29]. Mit-sunobu inversion of A to give B was the key step, and the diol C could be purified by recrystallization. 

Z,9S,10 )-9,10-Epoxyhenicos-6-ene (13) is the female sex pheromone of moths such as ruby tiger moth (Phragmatobiafuliginosa), fruit-piercing moth (Oraesia excavata), and painted apple moth (Teia anartoides). Scheme 23 summarizes Shi s synthesis of 13 based on Sharpless asymmetric dihydroxylation (AD) [36]. Mori synthesized 13 employing lipase to prepare A (Scheme 24) [37]. Alkylation of the acetylide anion C was possible neither with tosylate nor with iodide, but triflate B could alkylate C to give D. 

Scheme 69 summarizes Mori s synthesis of 45, in which was employed Sharpless asymmetric dihydroxylation (A B) as the key-step [101]. 

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation 26)43. Horner-Emmons condensation of phospho-nate 36 with a /J-aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquini-dine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

In studies directed toward the total synthesis of tedanolide [38], the addition of y-substituted ketene acetal 60 to aldehyde 84 generated unsaturated ester 85 in 62% yield (Scheme 30). The resulting double bond could be further functionalized by applying Sharpless asymmetric dihydroxylation conditions. Hence diol 86, which represents the mismatched case due to unfavorable... 

More recently, in light of the development of the Sharpless asymmetric dihydroxylation protocol [20], we have approached the synthesis of diols such as 14 (Scheme 2) from the alkene. Thus, treatment of the alkenyl D-glucosides 15 vmder the conditions of the Sharpless dihydroxylation gave a range of diols 16 with varying diastereoisomeric excesses (Table 1). One of these mixtures of diols, upon recrystallization, yielded the pure diastereoisomer, namely the diol 14. This procedure now gives a very rapid and efficient entry into one of the precursor diols for the synthesis of the optically-pure epoxides [21]. 

The quinoline portion of the target alkaloids was prepared by condensing p-anisidine 9 with ethyl propiolate, followed by bromination. Coupling of 10 with the boronic ester 8 proceeded to give 11, the intermediate for the synthesis of both 1 and 2. Selective direct epoxidation of 11 using the usual reagents failed, but Sharpless asymmetric dihydroxylation was successful, providing the diol in > 96 4... 

The Sharpless asymmetric dihydroxylation has played a prominent role in enantioselecitve organic synthesis. Two groups have recently reported improvements in the procedure. Osmo E.O. Horni of the University of Oulu, Finland has found (J. Org. Chem. 2004,69,4816) that sodium chlorite is a more efficient reoxidant than is the usual K,[Fe(CN)J. Carlos A.M. Alfonso of the Instituto Superior , Lisbon has reported (J. Org. Chem. 2004,69,4381) that the asymmetric dihydroxylation can... 

Salinosporamide synthesis 196 Sharpless asymmetric dihydroxylation (see also Osmylation) 84,89, 141, 189 Sharpless asymmetric epoxidation 32,141 Silane, allylic synthesis 43 Sonogashira coupling (see Pd)... 

Anti-tumor compound (205)-irinotecan (1) was prepared in 13 steps with an overall yield of 1.15 % for the longest linear synthesis. The short and selective preparation of aryl iodide 11 features two key steps - ortho metalation and Sharpless asymmetric dihydroxylation. In only one step 11 is transformed into the target molecule 1 by application of a radical domino annulation with isonitrile 15. This method gives access to the broad family of campthotecin derivatives because of the quite impressive generality of the substrates that can be employed. 

The synthesis of L-daunosamine began with the condensation of trans-crotonaldehyde (56) with dibenzylhydrazine (Scheme 17). Sharpless asymmetric dihydroxylation of the resulting ( )-a, (3-unsaturated hydrazone 57 afforded the syn-diol 58 (70% yield, 89% ee by HPLC), and silylation with chlorodimethyl-vinylsilane then provided the radical cyclization precursor 59 in 98% yield. In the key step, exposure to thiyl radicals generated from PhSH and AIBN led to radical cyclization of dibenzylhydrazone 59. The unstable cyclic intermediate was then directly treated with fluoride to afford vinyl adduct 60 in 77% yield (dr 91 9, H NMR). In control experiments with corresponding monosilyl derivatives, the (3-O-silyl... 

Both resolution and Sharpless asymmetric dihydroxylation were successful in the synthesis of Crixivan but the best method is one v e shall keep till later. Only one stereogenic centre remains, and its stereoselective formation turns out to be the most remarkable reaction of the whole synthesis. The centre is the one created in the planned enolate alkylation step,... 

Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis-amino-indanol for the synthesis of Crixivan, This process is very much the cornerstone of the whole synthesis. During the development of the first laboratory route into a route usable on a very large scale, many methods were tried and the final choice fell on this relatively new type of asymmetric epoxidation. The Sharpless asymmetric epoxidation works only for allylic alcohols (Chapter 45) and so is no good here. The Sharpless asymmetric dihydroxylation works less well on ris-alkenes than on trans-alkenes, The Jacobsen epoxidation works best on cis-alkenes. The catalyst is the Mn(III) complex easily made from a chiral diamine and an aromatic salicylaldehyde (a 2-hydroxybenzaldehyde). 

A stereocontrolled synthesis of the /ra j-tetrahydrofuran units in Annonaceae acetogenins that relies on the Sharpless asymmetric dihydroxylation protocol is outlined in Scheme 60 <1999TA2551>. In the first step, the disubstituted double bond of the starting material is dihydroxylated followed by monoprotection as a methoxymethyl ether. Einally, a cobalt-catalyzed oxidation using molecular oxygen as oxidant furnishes the /ra j-tetrahydrofuran. 

---