1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71, fax (3472) 35 60 66, e-mail: email@example.com; 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.
2006 Springer Science+Business Media, Inc.
Chemistry of Natural Compounds, Vol. 42, No. 4, 2006
IN NUCLEOPHILIC ADDITION REACTIONS
G. Yu. Ishmuratov,
R. Ya. Kharisov,
E. R. Latypova,
and R. F. Talipov
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.
organometallic reagents, natural cyclic
-enone monoterpenoids, Michael reaction, 1,2- and 1,4-addition
), pulegone (
), piperitone (
), menthenone (
), carenone (
), and verbenone (
) 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 .
ADDITION OF ORGANOMETLLIC REAGENTS.
The ability of nucleophiles to add to
-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
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-
) as an example. Addition of allyl-, crotyl-, and
at -15°C leads exclusively to formation of allyl alcohols
, the 1,2-addition products.
Increasing the temperature to 0°C for the reaction with 3,3-dimethylallyl Grignard reagent (
) gives a mixture (2:1) of the
) and 1,4- (
) adducts . The reaction with secondary 3-pentenylmagnesium chloride (
) at 20°C
gave the 1,4-addition product
as the dominant one.