Indanols alkylated

Fraction 8 (Figure 5 5) is mostly alkylated phenols and indanols with a trace amount of smaller alkanes. The base line shift is due to the co-elution of several large phenolic species in many isomeric forms. Fraction 9 (Figure 5-6) does not contain any alkanes. The ratio of the o-cresols to m, p-cresols increases from fraction 8 to 9. Both m-cresol and p-cresol are structurally longer than o-cresol. Some long aromatic species such as biphenyls also appear in this fraction. Compared to fraction 8, the phenols in fraction 9 are of shorter size... 

The biradical benzo-l,2 4,5-bis(l,3,2-dithiazolyl) (BBDTA) is known in the literature but characterization is incomplete. A new study reports the electronic, molecular, and solid-state structure of BBDTA.224 The lifetime of an alkyl phenylglyoxalate-derived 1,4-biradical has been estimated, using the cyclopropylmethyl radical clock , to be in the range 35—40 ns.225 The indanols (88) and their C(3) methyl and trideuteromethyl analogues have been prepared from phenyl benzyl ketone via photo-cyclization of an intermediate 1,5-biradical species.226,227 Selectivity for these products over their C(l) epimers is high but is profoundly effected by substitution in the benzyl ring or the alkyl side-chain. The findings are rationalized in terms of the conformational preference of the intermediate 1,5-biradicals. 

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). 

Not all organic chemists can be Involved in such exciting projects as the launching of a new anti-AIDS drug. But the chemistry used in this project was invented by chemists in other institutions who had no idea that it would eventually be used to make Crixlvan. The Sharpless asymmetric epoxlda-tion, the catalytic asymmetric reduction, the stereoselective enolate alkylation, and the various methods tried out for the enantiomerically pure amino indanol (resolution, enzymatic kinetic resolution) were developed by organic chemists in research laboratories. Some of these famous chemists like Sharpless invented new methods, some made new compounds, some studied new types of molecules, but all built on the work of other chemists. 

Indane oxide (109) undergoes a pH-independent reaction to form 4-indanol (115), and part of this product is formed by a 1,2-alkyl migration.96 However, most of the 4-indanol is formed as a result of the isomerization of 8,9-indane oxide to 4,9-indane oxide (111) via an oxygen walk. 96a,b A minor amount of 5-indanol (116) is... 

Benzyl-1-indanol 32, readily available in a few steps from 1-indanone, has been converted into 2-benzylindene 33 in various ways [66 - 68]. Treatment of 32 with orthophosphoric acid in chlorobenzene, for example, gives 33 as the sole product. However, use of polyphosphoric acid in the same solvent effects clean cyclodehydration of both 32 and 33 giving the mono-/uso-diindane 34 in high yield [65]. Several cenfro -alkylated derivatives of 34, including the methyl... 

P-carbon elimination which is facilitated by the release of the ring strain of a four-membered carbocycle via C—C a-bond cleavage, yielding an alkyl-Rh species. The key aryl-Rh intermediate was next delivered by a [1,4]-Rh migration. " Finally, the insertion of the C—Rh bond into the ketone moiety and protonation of the Rh—O bond furnishes the desired substituted indanol products. 

In 2013, the Chi group realized an NHC-catalyzed asymmetric p-functional-ization reaction of aldehydes via the transformation of saturated aldehydes to formal Michael acceptors via double oxidation. By using the catalyst derived from the chiral amino indanol triazolium salt in combination with quinone as the oxidant, the p-aryl substituted saturated aldehydes were converted to the o,p-unsaturated acyl azolium intermediates which further reacted with 1,3-dicarbonyl compounds or p-keto esters to generate the corresponding 5-lactones. It was found the use of LiCl and 4 A MS as additives was beneficial to improve the ee s of the products. Notably, the p-alkyl substituted saturated aldehydes were not viable substrates, probably due to the reduced acidity of the p-C—H bonds (Scheme 7.118). 

Figure 7.9 The side reactions occurring during the condensation of phenol with acetone. The formation of o.p-BPA isomers (1), mesityl oxide (2), the chromans (3 and 4). trisphenol (5). l,1.3-trimethyl-5-indanol (6), alkylated phenols (7) and 2,2.4-trimethylchromen (8) [40,41,43,45).

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, 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... 

Another auxiliary that proved to be useful as a base for enolate alkylations is cis-l-amino-2-indanol 37 developed by researchers at Merck, Sharp, and Dhome. Both enantiomers of the amino alcohol are commercially available in bulk. The alkylation method was elaborated for a synthesis of indinavir, the orally active HIV protease inhibitor that emerged as a major drug for treatment of AIDS. Thus, N-acylated Af,0-acetal 38 was converted into the lithium enolate and subsequently treated with allyl bromide to give the alkene 39 in excellent chemical yield and diastereoselectivity. The conversion into indinavir reveals that the amino alcohol 37 functions both as auxiliary and chiral building block (Scheme 4.8) [26]. 

The reported organic bifunctional catalysts possessing both hydrogen bond donor and acceptor moieties are often derived from the cinchona alkaloids. Tan and coworkers developed the simple and readily available amino-indanol 95 as an efficient bifunctional organocatalyst for the enantioselective Diels-Alder reaction of 3-hydroxy-2-pyridones 94 (Scheme 38.26) [40]. Besides maleimides 80, alkyl vinyl ketones were also suitable dienophiles for this catalytic system. 

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