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The transformation of ene-allene 75a to tetrahydroazepine 189 represents a formal
intramolecular ene-reaction of type III (Scheme 3.44). 130 This type is characterized by terminal
placement of the double bond in the “ene” unit, thereby leading to formation of the largest ring
possible (191 to 192).
Scheme 3.44 Type III intramolecular ene reaction.
Type III
intramolecular ene reaction
Z
H
∆
Z
H
191 192
O
O
H b
H a
S
350 o C
~100%
193 194
FVP 500 o C
60%
O
O
196 197
There are only a few examples of type III ene reactions and these generally require very high
temperatures to occur. For example, the thermal rearrangement of ortho-allylbutenyl benzene
193 occurs at 350 °C to give a mixture of fused benzocyclononadienes 194 and 195 in
quantitative yield. 131 Similarly, thioaldehyde 196 undergoes an intramolecular ene reaction under
flash vacuum pyrolysis (FVP) at 500 °C affording a thialactone 197, in a rare example of 7-
membered ring formation. 132 The high temperature required for this reaction to occur can be
attributed to the strained nature of the transition state 198 required for an ene reaction. Therefore,
the formation of tetrahydroazepine 189 via a Rh(I)-catalyzed cycloisomerization reaction of 75a
at 90 °C is an intriguing result. Moreover, azepines are an important synthetic target due to their
presence in a variety of natural products (cephalotaxanes, Stemona and Securinega alkaloids,
133, 134
Figure 3.4).
74
H a
S
H b
+
H
H
H b
195
S
198
O
O
H a