Spiro enantiomerically pure

Tris-spiro compounds have been generated from hexachlorocyclotriphosphazene by substitution with dihydroxyby-pyridine derivatives (Equation 31) <1999IC5457>. Treatment of hexachlorocyclotriphosphazene with 2equiv of biphenol or binaphthol yields only the / >-compounds 25 and 176. Enantiomerically pure cyclotriphosphazenes were generated from the (R)- or (Tl-forms of binaphthol (Equation 32) <1999EJI1673>. 

A. Vasella, P. Uhlmann, C. A. A. Waldraff, F. Diederich, and C. Thielgen, Fullerene sugars Preparation of enantiomerically pure, spiro linked C-glyco-sides of C50, Angew. Chem. Int. Ed. Engl., 31 (1992) 1388-1390. 

The cyclic ammonium ylide/[l,2]-shift approach has been successfully applied by West and Naidu to a key step in the total synthesis of (—)-epilupinine, one of the biologically active lupin alkaloids. Cu(acac)2-catalyzed diazo decomposition of enantiomeric pure diazoketone 160 in refluxing toluene generates a spiro ammonium ylide 161 and 162, which then undergoes [l,2]-shift to give rise to a quinolizidine skeleton as a mixture of diastereomers (95 5) (Scheme Major diastereomer 164 has enantiomeric purity of 75% ee. The partial retention of stereo-... 

J. J. Gaudino and C. S. Wilcox, A concise approach to enantiomerically pure carbocyclic robose analogues. Synthesis of (4S, 5R, 6R, 7R)-7-(hydroxymethyl)spiro[2.4Jheptane-4,5,6-triol-... 

Recently, they have synthesized enantiomerically pure 1,3-thiazolidine-derived spiro-(3-lactams [111] (Scheme 37) using Staudinger ketene-imine reaction starting from optically active lV-boc-1,3- thiazolidine-2-carboxylic acid derivatives and imines, thus confirming the generality of the earlier reported 1,3-thiazolidine-derived spiro-(3-lactams. 

Recently, Bittermann and Gmeiner [49] have provided a novel protocol for the synthesis of enantiomerically pure spiro-p-lactams 190 and characterized them as efficient p-tum nucleators (Scheme 44). 

Enantiomerically pure 1,3-thiazolidine-derived spiro /3-lactams 505 and 506 were stereoselectively synthesized by means of a Staudinger ketene-imine reaction in the presence of 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) starting from optically active A -BOC-l,3-thiazolidine-2-carboxylic acid derivatives 504 and imines (Scheme 127). The reactions were stereoselective and afforded spiro-/3-lactams with a /ra r -configuration. The spiro-/3-lactams 505 and 506 were transformed into enantiomerically pure chiral monocyclic /3-lactams 507 and 508... 

Vasella, A, Uhlmann, P, Waldraff, C A A, Diederich, F, Glycosylidenecarbenes. 9. Fullerene sugar preparation of an enantiomerically-pure, spiro-bound C-glycoside of Ceo, Angew. Chem. Int. Ed. Engl, 31, 1388-1390, 1992. 

Banks, M. R., Cadogan, J. I. G., Gosney, I., Grant, K. J., Hodgson, P. K. G., Thorburn, P. Synthesis of enantiomerically pure (5S)-4-aza-2-oxa-6,6-dimethyl-7,10-methylene-5-spiro[4.5]decan-3-one, a novel chiral oxazolidin-2-one from (-)-camphene for use as a recyclable chiral auxiliary in asymmetric transformations. Heterocycles 1994, 37,199-206. 

Enantiomerically pure spiro oxindoles (Scheme 35) were prepared by using solid-supported N-cinnamoyl Evans oxazolidinone (164) [265]. Thus, chiral oxazolidi-none prepared from L-tyrosine was attached to a Merrifield resin and then N-acylated with the required unsaturated acyl chloride such as cinnamoyl chloride (not shown). The resin (165) was then suspended in aqueous dioxane and treated with proline and N-phenyl isatin at 80-90 °C overnight to give a highly substituted spiro compound (167). 

Use of the enantiomerically pure alcohol 211 revealed a surprising stereospecificity. One enantiomer 215 gave (mostly) the required diastereoisomer 216 and hence the iodolactone 217 having the right stereochemistry at the spiro centre and at the lactone centre in the new ring. Removal of iodine, selective oxidation and addition of a d1 reagent gave (—) -cinatrin B. 

Dihydro-2-isopropyl-3.6-dimethoxypyrazine, a bis(lactim)ether, is converted into the 5-di-azo compound 1 by lithiation and diazo group transfer. The intermediate diazo compound reacts at room temperature with olefins such as cyclohexene to produce the cyclopropane derivatives with excellent diastereoselectivity . The derivative from cyclohexene is hydrolyzed by acid treatment to give methyl 7-cv(cfo-aminobicyclo[4.1.0]hcptane-7-carboxylate. The bis(lac-tim)ether diazo compound 1 is also involved in an exceptional asymmetric [2 + 1J cycloaddition producing cnantiomerically pure cyclopropenc derivatives4. Thus, reactions of the diazo compound with monosubstituted alkynes afford the spiro compounds as one diastereomer. Hydrolytic removal of the auxiliary and protection of the amino group provides enantiomerically pure methyl l-amino-2-arylcyclopropene-l-carboxylates in moderate overall yield. 

The imine (101) derived from a 2-aryltryptamine and ethyl glyoxylate undergoes a diastereo-selective spirocyclization to the indolenine (102) (Equation (27)). Replacement of the ethyl ester by chiral esters, such as the 8-phenylmenth-3-yl ester, leads to asymmetric induction at the spiro carbon atom <90HCA439>. Imines derived from tryptophan esters have also been studied as substrates for the Pictet-Spengler cyclization (e.g., <87tlii31 . Enantioselective cyclizations have made use of enantiomerically pure aldehydes and tryptophan esters <92H(34)517, 93JCS(pi)43i, 93T8589>. 

On the basis of the previous results. Park, Jew, and co-workers [101] developed in 2009 an efficient synthetic methodology for enantiomerically pure a-alkyl-a,3-diaminopropionic acid. They described the asymmetric PTC alkylation of Af(l)-Boc-2-phenyl-2-imidazoline-4-carboxylic acid /cr/-butyl esters (52) with propargyl, allyl, and substituted benzyl bromides under catalysis with the binaphthalene-derived PTC XXV (Scheme 8.19). Alkylated products were obtained in high yields with excellent enantioselectivities and their acidic hydrolysis furnished corresponding optically active a-alkyl-a,(3-diaminopropionic acids. Another example of PTC alkylation of heterocyclic compounds, namely 1-cyanotetrahydro-(3-carbolines using a binaphthyl-modified V-spiro-type catalyst L, was reported by Maruoka and co-workers [103]. 

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