Spiroketals chiral

Chiral 2-alky 1-1,3-propanediols.i Reaction of ( —)-menthone (1) with the bis(trimethylsilyl)ether 2 catalyzed by trimethylsilyl triflate gives the more stable equatorial isomer (3) of a spiroketal. Ring cleavage of the equatorial bond of the... 

Martin et al. (289) utilized the chiral bicyclic lactone 88 for a total synthesis of (+)-phyllanthocin (Scheme 6.62). Cycloaddition of 88 to acetonitrile oxide, generated in situ from hydroximoyl chloride (89), furnished cycloadduct 90 in 45% yield together with other regio- and stereoisomers. After several steps, methyl glycoside (91) could be obtained. From this, reduction-hydrolysis gave the aldol that was subjected to acid-catalyzed spiroacetalization to produce spiroketal (92), and eventually (+)-phyllanthocin (93) after two additional steps (289). The... 

Tetr 39 2323 (1983) (Recent Advances in the Preparation and Synthetic Applications of Oxiranes) 43 3309 (1987) (Synthetic Routes to Tetrahydrofuran, Tetrahydropyran, and Spiroketal Units of Polyether Antibiodcs and a Survey of Spiroketals of Other Natural Products) SO 8885 (1994) (Chemical and Biological Synthesis of Chiral Epoxides)... 

The catalyst [Pd(Me-DUPHOS)(MeCN)2](BF4)2 was also effective in the alternating asymmetric copolymerization of aliphatic a-olefins with carbon monoxide [27,28]. The polymer synthesized in a CH3N02-CH30H mixture has both 1,4-ketone and spiroketal (10) units in the main chain. The propylene-CO copolymer consisting only of a 1,4-ketone structure shows [ ]D +22° (in (CF3)2CHOH), and the optical purity of the main chain chiral centers is over 90% as estimated by NMR analysis using a chiral Eu shift reagent. 

General and stereoselective synthesis of spiroethers and less thermodynamically stable spiroketals have recently been developed by Hadded and coworkers129,130. The key step is the intramolecular photocycloaddition of chiral dioxinones of type 305 to dihydropyrones. Subsequent fragmentation of the produced four-membered ring provides, after oxidative enlargement of the cyclic ketone, the thermodynamically less stable spiroketal 310 (R = H) as was demonstrated on photoproduct 308 (Scheme 66). 

Spiroketalization. The synthesis of talaron ycin B (3) with four chiral centers by cyclization of an acyclic precursor presents stcrcot hcmical problems. A solution involves cyclization of a protected (3-hydroxy ketone witii only one chiral center. Because of thermodynamic considerations (i.e.. all substituents being equatorial and the anomcric effect), cyclization of 1 with HgCl, in CH,CN lollowcd by acetonation results in the desired product (2, 65% yield) with a stereoselectivity of —10 1. Final steps involve conversion of the hydroxymethyl group to ethyl by tosylation and displacement with lithium dimethylcupratc (80% yield) and hydrolysis of the acetonidc group. 

Spiroketal cyclization. Intramolecular spiroketal cyclization via Michael addition of an alcohol to a chiral a,p-unsaturated sulfoxide can proceed with high stereoselectivity. Reactions with KH are more stereoselective than those with NaH or n-BuLi. Thus cy-... 

The total synthesis of milbemycin-p developed by Williams et al. [124] involves construction of three units the spiroketal moiety (A), carbon chain with a remote chiral centre at C-12 (B) and the substituted benzoic acid (C). Unit (A) is prepared starting from citronellol (154), while unit (B) was prepared starting from (-)-(3S)-citronellal (162) (Scheme 20). A and B were joined after transmetalation of the tetrahydropyranyl ether 166 to give 167 (Scheme 21), which is allowed to react with the aldehyde A to give 168. Further steps are shown in scheme 22. 

A spiroketal bisphosphine (R R,R)-38a derived chiral Au complex was found to be an efficient catalyst for asymmetric cyclopropanation of diazooxindoles with a broad range of aUcenes, providing a highly diastereo- and enantioselective approach for spiro cyclopropyloxindoles (Scheme 41) [47]. These results further demonstrate the special advantage of rigid spiro ligands in Au-catalyzed reactions. 

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