Indanones basicity

This has become something of a standard reaction, since several authors have successfully used different chiral catalysts to effect the conversion in very high chemical and enantiomeric yield. Bergson and Langstrom (41) were the first to show that acrolein and a-isopropylacrolein added to 2-carbomethoxy-l-indanone (A in eq. [6]) in benzene in the presence of the strongly basic tertiary amine (/ )-( + )-2-(hydroxymethyl)quinuclidine to yield optically active ketoesters. Unfortunately, the quinuclidine catalyst was not enantiomerically pure, and neither the chemical nor the optical yields of the aldehydo ester analogous to B (eq. [6]) were reported. 

Thiopyrans have, in general, been less thoroughly investigated. The isothiochroman-4-one (245) on irradiation in basic methanol is converted to the indanone (246)199 a pathway involving electrocyclic ring opening and the formation of the intermediate (247) may be implicated. An alternative... 

The first examples of asymmetric Michael additions of C-nudeophiles to enones appeared in the middle to late 1970s. In 1975 Wynberg and Helder demonstrated in a preliminary publication that the quinine-catalyzed addition of several acidic, doubly activated Michael donors to methyl vinyl ketone (MVK) proceeds asymmetrically [2, 3], Enantiomeric excesses were determined for addition of a-tosylnitro-ethane to MVK (56%) and for 2-carbomethoxyindanone as the pre-nudeophile (68%). Later Hermann and Wynberg reported in more detail that 2-carbomethoxy-indanone (1, Scheme 4.3) can be added to methyl vinyl ketone with ca 1 mol% quinine (3a) or quinidine (3b) as catalyst to afford the Michael-adduct 2 in excellent yields and with up to 76% ee [2, 4], Because of their relatively low basicity, the amine bases 3a,b do not effect the Michael addition of less acidic pre-nucleophiles such as 4 (Scheme 4.3). However, the corresponding ammonium hydroxides 6a,b do promote the addition of the substrates 4 to methyl vinyl ketone under the same mild conditions, albeit with enantioselectivity not exceeding ca 20% [4],... 

Crystallization-induced asymmetric transformation has already been described by Leuchs in 1913 during the resolution of 2-(2-carboxybenzyl)-l-indanone with brucine.34 In this case spontaneous racemization occurred. More recently researchers at Sanofi observed spontaneous racemization during the resolution of 3-cyano-3-(3,4-dichlorophenyl)propionic acid (7), most likely as a result of the basic resolving agent [>-(-)-N-1 n etli y I g I near nine [d-(-)-MGA] (8) (Scheme 7.6).35 The enantiopure cyano acid, obtained in 91% overall yield, is subsequently reduced to (+)-4-amino-3-(3,4-dichlorophenyl)-l-butanol (9), a key intermediate in the phase 2 synthesis of tachykinin antagonists. 

Indanones are very useful and versatile intermediates in the synthesis of metallocene catalysts. Scheme 1 has the synthetic scheme originally used for the preparation of 2-alkyl-4-aryl-substituted ansa metallocenes [9-11]. In the first part of this sequence, the biaryl unit is assembled and the missing carbon atoms are introduced as a side chain. The reaction of 2-phenylbenzyl bromide with malonic acid ethyl ester under basic conditions, followed by a decarboxylation, affords the 2-(2-phenylbenzyl)propionic acid. Chlorination and Friedel-Crafts acylation yields the 2-methyl-4-phenylindanone in 93 % yield. From here, only a few standard transformations are required to complete the synthesis, finally yielding the desired metallocene. 

The condensation of 1-indanones and benzaldehydes giving 2-benzylidene-1-indanones is a classic approach to Cs-diindanes. However, the condensation of 46 and 47 and their derivatives under basic conditions often leads to dimers of 48, the structure of which has been a matter of long debate [72]. Recent studies [73,74] confirmed the constitution and configuration of the major product formed either directly from 46 and 47 [74] or by directed dimerization of 48 [73] as the dibenzotriquinanedione 49 (Scheme 8). This dimer represents an ex-tended diindane bearing a central spiro- and/hso-annelated czs-diphenylcyclo-pentane unit with the two phenyl groups oriented syn to the /hso-diquinane moiety and cis to the spiro-indanone carbonyl group. 

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