Preparation of Highly Functionalized 1-Indanones
SCHEME 5. P r ep a r a tion of Keton es 1m -o
lobenzenes with magnesium turnings is often trouble-
some. These difficulties can be circumvented by using the
highly reactive Riecke magnesium. The Grignard reagent
obtained from 17 was treated with the Weinreb amide
18, which was prepared from ethyl glycolate in two steps.
Deprotection of the primary hydroxy group gave the
hydroxy ketone 19 with an overall yield of 77%. Surpris-
ingly, the mesylation of the hydroxy group in 19 turned
out to be difficult. The reaction of 19 with MsCl in
pyridine gave the R-chloro ketone instead of the desired
mesylate.12 Replacement of MsCl by Ms2O afforded 1m ,
but in low yields even in the presence of DMAP. A
satisfactory yield was achieved by deprotonation of the
hydroxy group with BuLi followed by treatment with
MsCl.
The synthesis of methyl ester 1n started with a
Sonogashira14 coupling of methyl o-iodophenylacetate
1313 with trimethylsilylacetylene and subsequent desi-
lylation. The arylacetylene 14 could be regioselectively
hydrated by utilization of a gold catalyst to give the
acetophenone 16a .15 Compound 16b bearing a nitrile
group instead of the ester group was obtained from
o-methylacetophenone by a four-step sequence. The
introduction of the mesyloxy group took place again with
the hypervalent iodine reagent PhI(OMs)OH and pro-
vided the ketones 1n ,o.
(A-D). Scheme 6 depicts a selection of methods. One of
the oldest methods is the intramolecular Friedel-Crafts
acylation of 3-arylpropionic acid derivatives (A116). An-
other method to form the arene-carbonyl-C bond of
1-indanones is based on the Pd-catalyzed cyclization of
3-(2-iodoaryl)propionitriles (A217). The formation of the
C1-C2 bond (B) was relatively seldom used and was
performed by an intramolecular Claisen condensation
(Dieckmann condensation, B118). Most methods are based
on the formation of the C2-C3 bond (C) and include
intramolecular SN reactions (C119), the cyclization of
2-(alkynylaryl)allenes (C220), or the insertion of ketocar-
benes, generated from diazoketones by Rh-catalysis, in
C-H bonds of o-alkyl groups (C321). There exist also some
photochemical routes to 1-indanones. Thus, 1,2-diketones
were cyclized in the course of a Norrish-Yang reaction
(C422) and also enones (C523) and inones (C624) were used
as reactants for the preparation of 1-indanones. Further-
more, the simultaneous formation of two C-C bonds form
the basis of some methods (AB1,25 AD1,26 and BC127).
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Syn th esis of 1-In d a n on es: Kn ow n Meth od s. To
classify the photochemical route to 1-indanones described
herein, the hitherto known methods to prepare these
bicyclic ketones should be briefly outlined. These methods
may be systematized regarding C-C bonds tied to
construct the five-membered ring of the indane skeleton
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(12) This behavior was already observed previously: see ref 3c.
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J . Org. Chem, Vol. 69, No. 22, 2004 7585