formed when employing allylic 1,2-diols in Prins cyclization readily undergoes ring
contraction through a pinacol rearrangement to give 3-acyl THF 135 (Scheme 35)
[72–74]. The difficulties associated with attenuating the Prins–pinacol pathway
must be considered when planning a synthetic strategy to access THP rings bearing
an alcohol.
The 2,6-cis THP ring of leucascandrolide A has been approached by classical
Prins methods as well as been a testing ground for novel extensions of this reaction.
Kozmin and coworkers performed a vinylogous transesterification of alcohol 136 to
afford Prins cyclization precursor 138 (Scheme 36) [75, 76]. Subsequent treatment
of enol ether 138 with trifluoroacetic acid initiated a Prins cyclization, and basic
ester hydrolysis provided the 2,4,6-cis THP alcohol 139 in 77 % as a single
diastereomer.
O
R"
O
O
º
LA
X
OH
R'
R
R"
R
OH
R'
OH
R"
R
R'
R
O
R"
H
OH
R'
O
R"
R
O
R'
H
O
R"
R
R'
O
Prins
pinacol
131
132
133
134
135
Scheme 35 Allylic 1,2-diols undergo Prins–pinacol reactions
O
X
R
O
R
O
R
O
H
Nu
O
Nu
R
O
X
O
O
O
H
Nu
O
Nu
R
R
R
R
O
O
Nu
R
R
Nu
º
LA
º
LA
Stereochemistry of Prins cyclization for E-alkenes
Stereochemistry of Prins cyclization for Z-alkenes
122
123
124
125
127
128
130
129
126
(eq 1)
(eq 2)
Scheme 34 Relative stereochemistry in the Prins cyclization is dictated by alkene geometry
Synthesis of Saturated Tetrahydropyrans
65