1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71, fax (3472) 35 60 66, e-mail: kharis@anrb.ru; 2) Bashkir State University, 450074, Ufa, ul. Frunze, 32, fax (3472)
72 32 29. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 303-316, July-August, 2006. Original article submitted
February 13, 2006.
0009-3130/06/4204-0367
©
2006 Springer Science+Business Media, Inc.
367
Chemistry of Natural Compounds, Vol. 42, No. 4, 2006
NATURAL CYCLIC
α
,
β
-ENONE MONOTERPENOIDS
IN NUCLEOPHILIC ADDITION REACTIONS
G. Yu. Ishmuratov,
1
R. Ya. Kharisov,
1
UDC 542.943.5+542.957+547.596
E. R. Latypova,
2
and R. F. Talipov
2
The literature on transformations of natural cyclic α,β-enone monoterpenoids into compounds of more
complicated structure via 1,2- and 1,4-addition reactions was reviewed. The data were systematized
according to the effects of the conditions and nature of the starting substrates on the selectivity of
the 1,2- and 1,4-addition reactions.
Key words:
organometallic reagents, natural cyclic
α
,
β
-enone monoterpenoids, Michael reaction, 1,2- and 1,4-addition
reactions.
Carvone (
1
), pulegone (
2
), piperitone (
3
), menthenone (
4
), carenone (
5
), and verbenone (
6
) are the most common
natural monoterpenoids that contain both a double bond and a carbonyl group conjugated to it and are interesting with respect
to directed synthesis.
The portion of these molecules that includes the vinyl and carbonyl groups acts as a unified system for which both
1,2- and 1,4-nucleophilic addition reactions are characteristic. It is rather difficult to predict accurately how a process will occur
in an actual situation because each molecule has its own peculiarities. Nevertheless, definite generalizations can be made based
on existing data, which are reviewed herein [1].
ADDITION OF ORGANOMETLLIC REAGENTS.
GENERAL CONCEPTS
The ability of nucleophiles to add to
α
,
β
-enones is very significant because the modifications of reagents and the
reaction conditions can direct a reaction preferentially to one of two possible pathways.
Grignard reagents and organolithium and -copper compounds are used most frequently for this in practice. Recently
reports of studies using organozinc and -manganese reagents [2-5] have appeared. However, they have not yet been widely
applied.
Depending on the reaction conditions, a Grignard reagent may give both the 1,2- and 1,4-adducts. Kinetically
controlled addition of an organomagnesium reagent at low temperatures favors formation of the 1,2-adduct whereas increasing
the reaction temperature leads primarily to formation of the thermodynamically more favorable 1,4-addition product. The
reactions of Grignard reagents can be illustrated using (R)-pulegone (R-
2
) as an example. Addition of allyl-, crotyl-, and
3-methyl-2-enyl derivatives
7a
-
d
at -15°C leads exclusively to formation of allyl alcohols
8a
-
d
, the 1,2-addition products.
Increasing the temperature to 0°C for the reaction with 3,3-dimethylallyl Grignard reagent (
9
) gives a mixture (2:1) of the
1,2- (
10
and
11
) and 1,4- (
12
and
13
) adducts [6]. The reaction with secondary 3-pentenylmagnesium chloride (
14
) at 20°C
gave the 1,4-addition product
15
as the dominant one.