Synthesis of Indanols

The biradical corresponding to 16a produces indanol 18 quantitatively, whereas the biradical from 16b undergoes disproportionation to form mainly 19. The quantum efficiency for the formation of 18 was 0.03 in hydrocarbon solvent, and 1.0 in methanol. In contrast, the total quantum yield for 16b was rather low (0.02-0.05) in both hydrocarbon and methanol solvents. These differences were ascribed to a considerably smaller dihedral angle between the carbonyl and t-butyl benzene in the triplet excited state of 16a in comparison to 16b, and a differing rotational freedom in the biradical 17 intermediate species. 

The product ratio (23/24 = 1/1.6) in solution indicated the preference for secondary versus primary H-abstraction, while this was opposite ( 7/l) in solid. A detailed study has shown that there are no indications of any significant stereoelectronic 

The Z/E ratio was reported to be opposite to that observed in earlier cases [9], ranging from 1 19 to 1 2.5 at between —72 °C and 90 °C in toluene, and reaching a value as low as 1 99 in methanol at 25 ° C. The formation of fc -indanol is explained by considering a larger rotational barrier of the 1,5-biradical for Z-forming geometry. 

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Meador and Wagnerhave reported an efficient photochemical synthesis of indanols (75) by the cyclization of the ketones (76). The process ultilizes the variant of the Norrish Type II reaction involving 6-hydrogen abstraction by the excited carbonyl group. The kinetic information collected for the reactions... 

SCHEME 3.63 Synthesis of indanols by 1,4-addition/aldol-type intramolecular cascade reaction. 

Seiser, T. Cramer, N. Rhodium(I)-Catalyzed 1,4-Silicon Shift of Unactivated Silanes from Aryl to Alkyl Enantioselective Synthesis of Indanol Derivatives. Angew. Chem., Int. Ed. 2010,49,10163-10167. 

Seiser T, Roth OA, Cramer N (2009) Enantioselective synthesis of indanols from tert-cyclobutanols using a rhodium-catalyzed C-C/C-H activatirai sequence. Angew Chem Int Ed 48(34) 6320-6323. doi 10.1002/anie.200903189... 

Seiser T, Cramer N (2010) Rhodium(I)-catalyzed 1,4-silicon shift of unactivated silanes from aryl to alkyl arantioselective synthesis of indanol derivatives. Angew Chem Int Ed 49(52) 10163-10167. doi 10.1002/anie.201005399... 

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... 

Phenol annelation.1 This modified methyl vinyl ketone can be used for synthesis of 5,6,7,8-tetrahydro-2-naphthol or 5-indanol by reaction with the lithium enolate of cyclohexanone or cyclopentanone, respectively. The former reaction is formulated in equation (I). 

Since the discovery of cis-1 -amino-2-indanol as a ligand for human immunodeficiency virus protease inhibitors and the development of a practical industrial process for the synthesis of either ris-isomers in enantiopure form, the remarkable properties of the rigid indane platform have been used extensively in an ever-increasing number of asymmetric methodologies. In addition to the use of this amino alcohol as a chiral auxiliary and ligand for asymmetric synthesis, it has found application as a useful resolution agent. Applications include amines, carboxylic acids, and alcohols. 

One of the few industrial examples of the asymmetric synthesis of halohydrins is in a process to the human immunodeficiency virus (HIV) protease inhibitor, Indinavir.190 The y,8-unsaturated carboxamide 23 is smoothly converted into iodohydrin 24 (92%, 94% de) (Scheme 9.34). (For more on the chemistry of the indanol, see Chapter 24.)191... 

Enantiomerically pure d.v-1 -amino-2-indanol and its derivatives have been used as ligands in numerous catalytic asymmetric carbon-hydrogen, carbon-carbon, and carbon-heteroatom bond formation reactions. The conformationally constrained indanyl platform has emerged as a particularly valuable backbone in a variety of catalytic processes leading to high levels of asymmetric induction. The aminoindanol 1 has also been used as a resolution agent (Chapter 8) as well as a chiral auxiliary (Chapter 24). For the synthesis of 1 see Chapter 24. 

This chapter focuses on the importance of cis-1 -amino-2-indanol as a chiral template in the development of new methodologies for the asymmetric synthesis of organic compounds. Other chiral auxiliaries are discussed in Chapter 23. The use of the amino alcohol 1 in resolutions is discussed in Chapter 8, whereas applications of 1 as a ligand are in Chapter 17. 

This alkylation strategy has been successfully implemented to the diastereoselective synthesis of a number of biologically active compounds,17 19 32 72 73 including the orally active HIV protease inhibitor Crixivan (>95% de)17-19 and nucleoside antibiotic (+)-sinefungin (51) (>99% de).72 The C-6 amine stereochemistry of (+)-sinefungin was set by a highly diastereoselective allylation of (lS,2/ )-l-amino-2-indanol-derived oxazolidinone 52 (Scheme 24.10). 

The chiral sulfonamide 45, which can be prepared in two steps from commercially available (I R,2S)-cis-1 -amino-2-indanol (44), was introduced by Ghosh and Onishi for the synthesis of enantiomerically pure anft -aldol products via titanium enolate19a (Scheme 2.2q). 

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). 

Annulation. Synthesis of 1-indanols from o-acylarylboronic acids and conjugated dienes involves iridium cycles. While dienes bearing electron-donating or electron-withdrawing substituent(s) are successfully used, the participating double bond is electron-richer. 

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