Chemistry Reference
In-Depth Information
In addition, the absolute stereochemical course of the enantioselective Michael
addition of 2-cyclohexenone can be rationalized by the previously proposed pretransi-
tion-state assembly. The enantioselective methodology is illustrated by application of
the synthesis of the key intermediate,
A
, for the enantioselective synthesis of caryophyl-
lene (Scheme 3.8 ).
R
1
H
R
1
BLA
2a
(20 mol %)
n
R
1
n
MeO
R
2
R
2
R
2
R
2
R
1
Ph
3
PO (25 mol %)
i-Pr
MeO
2
C
OTMS
O
O
R
1
= Me, -(CH
2
)
5
-
R
2
= H, Me
n = 1, 2
OH
79-89% yield
82-92% ee
i-Pr
Toluene, -20°C
Me
H
Me
H
Me
Me
ent
-BLA
2a
(20 mol %)
Me
Me
Me
Ph
3
PO (25 mol %)
MeO
2
C
H
Caryophyllene
Toluene, -20°C
MeO
OTMS
O
O
A
Scheme 3.8.
Gnanadesikan and Corey developed a new type of BLA
3
, derived from precatalyst
zwitterions and tributyltintrifl ate, for enantioselective synthesis of β - lactones from
ketene and aldehydes [14]. Activation of the precatalyst by tri-
n
- butyltintrifl ate pro-
duced the ion pair, which by reaction with ketene should form the intermediate. The
intermediate should be a suffi ciently strong Lewis acid to coordinate with the aldehyde
and generate the reactive complex. C-C bond formation, followed by extrusion of β -
lactone completes the catalytic cycle. It is noteworthy that β - lactone formation from
α-branched aldehydes was demonstrated for the fi rst time (Scheme 3.9 ).
Recently, Payette and Yamamoto developed a new BLA
4
and successfully applied
this catalyst system to enantioselective D-A reactions with 1- and 2-substituted cyclo-
pentadienes (CPs). Activation of oxazaborolidine with the super Brønsted acid
C
6
F
5
CHTf
2
was found to produce even more reactive catalyst BLA
4
[15] . Interestingly,
from the mixture of 1- and 2-substituted CPs, BLA
4
exclusively afforded adducts
from 2-substituted CP as single isomers. D-A adducts of the remaining unreacting 1-
substituted CP remarkably could be obtained through a one-pot process with more
reactive dienophiles such as quinone to afford highly diastero- and enantioselective
compounds with two consecutive quaternary carbon centers. To rationalize the observed
regio- and stereocontrolled D-A adducts, they proposed a hypothetical transition state
(Scheme 3.10 ).
In recent work, Balskus and Jacobsen applied modifi ed BLA
5
to the transannular
Diels-Alder (TADA) reaction [16]. Various sized macrocycles containing α , β -
unsaturated lactones and ketone could be cyclized to afford tricyclic
endo
products
