1-Indanols

Another chiral titanium reagent, 11, was developed by Corey et al. [17] (Scheme 1.24). The catalyst was prepared from chiral ris-N-sulfonyl-2-amino-l-indanol and titanium tetraisopropoxide with removal of 2-propanol, followed by treatment with one equivalent of SiCl4, to give the catalytically-active yellow solid. This catalyst is thought not to be a simple monomer, but rather an aggregated species, as suggested by NMR study. Catalyst 11 promotes the Diels-Alder reaction of a-bro-moacrolein with cyclopentadiene or isoprene. 

This result stands in contrast to hydrogenation of 2-oximino-]-indanone (R = H), which stopped spontaneously at the 2-amino-1-indanol stage under similar conditions (43). This latter result accords with the general exp>erience in reduction of aromatic -oximino ketones (35,37 38,39,40). The amino function usually severely inhibits hydrogenolysis of the alcohol. 

The cooxidation of thiophenol with indene by air in hydrocarbon solvents provides l-hydroperoxy-2-phenylthioindane 84 in 77% yield. Subsequent rearrangement afforded a mixture of trans and cis 2-phenylsulphinyl-l-indanols 85148 149 (equation 47). 

Imidazoles 775 /J-Iminosulphones 640 /J-Iminosulphoxides, synthesis of 69 Inclusion compounds 59, 287 Indanols 256 Indanones 338 Indenes 267 Indoles 323... 

Phenols, pAfa values of 586-589 Phenothiazine oxides, mass spectra of 130 2-Phenylsulphinyl-l-indanols, synthesis of 256... 

The DKR of secondary alcohols can be efficiently performed via enzymatic acylation coupled with simultaneous racemization of the substrates. This method was first used by BackvaU for the resolution of 1-phenylethanol and 1-indanol [38]. Racemization of substrate 18 by a mthenium catalyst (Scheme 5.11) was combined with transesterification using various acyl donors and catalyzed by C.antarctica B Hpase. From aU the acyl donors studied, 4-chlorophenyl acetate was found to be the best. The desired product 19 was obtained in 80% yield and over 99% ee. 

Lee K, SM Resnick, DT Gibson (1997) Stereospecific oxidation of R) and (S)-l-indanol by napthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4. Appl Environ Microbiol 63 2067-2070. 

Davies and Reider (1996) have given some details of the HIV protease inhibitor CRDCIVAN (INDINAVIR) for which (lS,2R)-c -amino indanol is required. Indene is epoxidized enantioselectively, using the lacobsen strategy (SS-salen Mn catalyst, aqueous NaOH and PiNO), to (lS,2/ )-indene oxide in a two-phase system, in which the OH concentration is controlled. Indene oxide was subjected to the Ritter reaction with MeCN, in the presence of oleum, and subsequent hydrolysis and crystallization in the presence of tartaric acid gives the desired amino indanol. 

Both enantiomers of (Z)-l-amino-2-indanol are available commercially. 

The amino indanol was placed in a 250 mL three-necked round-bottomed flask equipped with a magnetic stirrer bar under nitrogen. Dry methylene chloride (110mL) and triethylamine (6.7 mL) were then added. The reaction mixture was allowed to cool to 0°C before adding a solution of 2-chloro-sulfonyl pyridine (7.1 g in 50mL CH2C12) over 20 minutes. The mixture was stirred at this temperature for 1 hour. 

Table 11.8 Reduction of ketones using 7V-(2-pyridinesulfonyl)-l-amino-2-indanol as a ligand.

Prepare 6-methoxy-l-indanone (I) (JCS 1986(1962)) using polyphosphoric acid made by diluting 500 g of the commercial acid with 120 g 85% phosphoric acid. 2.5 g (I) in 176 ml ether and reflux one hour with 0.27 g lithium aluminum hydride. Cool and carefully add water and filter when bubbling stops (can use Celite filter aid). Dry and evaporate in vacuum and store twelve hours at -15° (under N2 if possible) to precipitate the white 6-methoxy-l-indanol (II) (recrystallize-n-hexane). 2.5 g (II) in 73 ml benzene and reflux one-half hour with 0.2 g p-toluenesulfonic acid. Cool, add water and separate the phases. Extract the aqueous phase with ether and combine with benzene phase and dry, evaporate in vacuum to get 5-methoxy-indene (III) (can distill 110-45/10). 1.53 g (III) and 1.39 g N.N-diethyl-aminoethyl-Cl.HCI in benzene (prepare the free base in benzene as described previously). Reflux four hours with 0.42 g sodamide, cool, wash with water and dry, evaporate in vacuum to get the indene analog of 6-methoxy DET as a dark liquid (can crystallize as oxalate). Alternatively, dissolve 2.51 g (III) in ether and treat (under N if possible) with 12 ml 1.6M buty-Li in hexane at 0-10°. After two hours cool to -30° and add 12 ml more of butyl-Li. Add ether suspension of 2.5 g N,N-diethylaminoethyl-CI. HCI over one-half hour and warm to room temperature. Filter, evaporate in vacuum to get the 6-methoxy-DET analog. 

Peglion, J.-L., Goument, B., Despaux, N., Chariot, V., Giraud, H., Nisole, C., Newman-Tancredi, A., Dekeyne, A., Bertrand, M., Genissel, P. and Millan, M. J. (2002) Improvement in the selectivity and metabolic stability of the serotonin 5-HTja ligand, S 15535 a series of cis- and troras-2-(arylcycloalkylamine)-l-indanols. Journal of Medicinal Chemistry, 44, 165-176. 

Sudo and Saigo153 reported the application of ds-2-amino-3,3-dimethyl-l-indanol derived l,3-oxazolidin-2-one 231 as a chiral auxiliary in asymmetric Diels-Alder reactions. The TV-crotonyl and TV-acryloyl derivatives were reacted with cyclopentadiene, 1,3-cyclohexadiene, isoprene and 2,3-dimethyl-l,3-butadiene, using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded the expected cycloadducts in moderate to high yields (33-97%) with high endo selectivities and high de values (92% to >98%). 

Monochlorotitanium complex 418, prepared from (l/J,25 )-Af-(2,4,6-trimethylbenze-nesulfonyl)-2-amino-l-indanol and titanium tetraisopropoxide followed by treatment with titanium tetrachloride effectively catalyzed the cycloaddition of a-bromoacrolein to cyclo-pentadiene, affording 366 with 93% ee (equation 125)259. Catalyst 418 induced an ee of 90% in the reaction of isoprene with a-bromoacrolein. 

Crucially, it was found22 that upon reaction of the vinylketene complex 42.a with 1-pentyne, the same product distribution was seen as for the direct thermolysis of 1-pentyne with the precursor carbene 43.a. The analysis was simplified by reduction of the crude reaction mixture with McMurry s reagent to produce a mixture of the isomeric indanols 44-46. 

The indanols 44 and 45 can only be the products of a formal [4 + 2] cycloaddition23 of the vinylketene complex 42.a with 1-pentyne. Note that upon reaction of 42.b with diethylpropynylamine a formal [2 + 2] cycloaddition65 is seen to take place, yielding the cyclobutenone 47 along with a tricarbonylchromium complex, tentatively identified as 48.66,67 As one would expect, the vinylketene complex 42.b underwent 1,2-additions with pyrrolidine and sodium methoxide in methanol, yielding 49 and 50, respectively. The CO-insertion step leading to vinylketene formation is reversible in some systems,51,68,69 but there is no evidence of this for complex 42.a. Heating a benzene solution of complex 42.a at 80°C under an atmosphere... 

The effect of changing the nature of the chromophore has been investigated by comparing the R2PI spectra of diasteromeric [C -M] (M = 2-butanol or 2-hexanol) complexes with the corresponding spectra with (R)-(- -)-l-phenylethanol (E ) and (/ )-(—)-indanol as chromophores. As for [C M], the diastereomeric [E M] (M = 2-butanol) and (M = 2-hexanol) complexes exhibit spectral signatures... 

Twelve out of 15 ligands show good to excellent yields. The only unreactive one is the indanol amin ligand 54 with only 3% conversion. Regarding enantioselectivities the best results were obtained with the acyclic ligands 49 and 51. It was therefore decided to investigate aliphatic ketones. 

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