O
O
R
R
X
Nu
kinetically-favored
axial attack
O
R
O
R
Nu
Lewis-acid
promoted
oxocarbenium
ion formation
O
R
R'
alkylation
oxocarbenium
O
R
X
+
Lewis Acid
+
1
2
1
2
Organometallic
Nucleophile
EWG
O
R
O
R
EWG
O
R
EWG
+B
+B
+HB
+HB
thermodynamically
-favored equatorial
arrangement
+ X LA
6
6
250
251
251
252
253
trans-254
255
cis-254
Lewis Acid = BF 3 ·OEt 2 , MgBr 2 ·OEt 2 ,
ZnCl 2 , ZnBr 2 , TMSOTf,
TiCl 4 , SnCl 4
X = OAc, OMe, OH
Nucleophile = Allyl/crotyl silanes, Allyl/crotyl stannanes,
Silyl enol ethers, Silyl ketene acetals,
Silyl hydrides, Metal cyanides, Alkyl zincs
Commonly:
Retrosynthesis
Mechanistic rationale for stereoselectivity
Epimerization of problematic substrates
(eq 1)
(eq 2)
(eq 3)
TS-A
Scheme 67 Reductive C2 functionalization: mechanistic and structural implications
O
R
OH
2
6
O 3 , MeOH
then Me 2 S
and HCl (aq)
OH
R
2
6
O
R
OMe
2
6
closure
O
R
R'
2
6
OH
R
O
2
6
OH
R'
closure
O
R
OAc
O
R
2
2
6
6
O
DIBAL-H
CH 2 Cl 2 , –78 °C
then Ac 2 O
DMAP, Py
OH
R
H
Lactol formation
a-Alkoxy ether formation
256
257
258
259
7
260
261
262
(eq 1)
(eq 2)
(eq 3)
(eq 4)
2
6
O
Scheme 68 Common methods for the synthesis of reductive C2 functionalization precursors
86
M.A. Perry et al.