Handbook of Functionalized Organometallics Applications in S

6.3 Nucleophilic Additions
oxy aldehydes are frequently used in total synthesis of complex targets such as
Discodermolide [190] or Roxaticin macrolide [191].
Match/mismatch effect: the addition of c-substituted allyltins to a-substituted
aldehydes leads to three contiguous asymmetric centers mostly with a good control
of each diastereoselectivity and is commonly applied in total synthesis such as
for Erythromycin [192] (Scheme 6.22). It has to be noted that when the reaction is
done with a chiral aldehyde and a chiral d-substituted allyltin, a ªmatching effectº
may happen when both partners imposed a convergent selectivity, or a ªmismatching
effectº when the facial selectivity is divergent [193]. Such a stereoconvergent
effect was used in the synthesis of the antitumor agent Azinomycin [194].
Mes
O
O
Scheme 6.22
OTES
OBOM OR
CHO
Mes
+ SnBu3 BF3.OEt2 CH2Cl2,-78ºC O
OTES
96%
dr = 8:1
OBOM OR
As an alternative to the use of Lewis acids, Brönsted acids, such as trifluoromethane
sulfonic acid, can be used for the allylation of aldehydes in EtOH/H 2O
[195]. Using the same idea, a chelation control can be carried out without any
Lewis acid simply by adding lithium salts such as LiClO 4 to the reaction mixture
[196].
6.3.1.2.2 Activation of the Allyltin Reagent
In situ transmetallation: the activation of the allyltin can be ensured by a transmetallation
with the Lewis acid prior to the addition on the carbonyl (also called
ªreversedº addition). The first example was reported with SnCl 4 [197] but other
Lewis acids such as TiCl 4, AlCl 3, InCl 3 can be used. The difference lies in the nature
of the transient allyl metal, which becomes a stronger Lewis acid, implying a
cyclic 6-membered transition state already involved in thermal or high-pressure
activated allylations. This changes the diastereoselectivity pattern of the reaction,
(E)-crotyltin giving an anti selectivity, when (Z)-crotyltin leads to syn selectivity. It
has to be noted that the transmetallation proceeds via the kinetic allylmetal, which
turns to the thermodynamic crotyltin. Under thermodynamic control, the homoallylic
alcohol is usually obtained with a high level of anti selectivity. The transmetallation
can be used with more sophisticated Lewis acids such as the C-2 symmetry
Corey's bromoborane, in order to induce a stereoselectivity dominated by the
chiral auxiliary [198] (Scheme 6.23).
O
OH
219