Page 1134 - Advanced Organic Chemistry Part B - Reactions & Synthesis

1110 The trans-3-methyl isomer appears to react through two conformers, with the axial
methyl conformer giving trans-2-methylcyclohexanol.
CHAPTER 12
Oxidations OH O OH
CH 3 O CH 3

61%
CH
CH 3 30% 3
CH 3

OH
9%
(via ketone)

Lithium triethylborohydride is more reactive than LiAlH and is superior for
4
epoxides that are resistant to reduction. 130 Reduction by dissolving metals, such as
lithium in ethylenediamine, 131 also gives good yields. Di-i-butylaluminum hydride also
reduces epoxides. 1,2-Epoxyoctane gives 2-octanol in excellent yield, and styrene oxide
gives a 1:6 mixture of the secondary and primary alcohols. 132 This relationship indicates
that nucleophilic ring opening controls the regiochemistry for 1,2-epoxyoctane but that
ring cleavage at the benzylic position is the major factor for styrene oxide.

O (i-Bu) 2 AlH OH
RCHCH + RCH CH OH
R hexane 3 2 2
H
R = C 6 13 100 : 0
H 14 : 86
R = C 6 5
Diborane in THF reduces epoxides, but the yields are low, and other products
are formed by pathways that result from the electrophilic nature of diborane. 133 Better
yields are obtained when BH 4 − is included in the reaction system, but the electrophilic
nature of diborane is still evident because the dominant product results from addition
of the hydride at the more-substituted carbon. 134

OH OH
O BH 3
CH 3 CH 3 (CH ) CHCHCH + (CH ) CCH CH
BH – 3 2 3 3 2 2 3
CH 3 4 78% 22%

The overall transformation of alkenes to alcohols that is accomplished by epoxi-
dation and reduction corresponds to alkene hydration. Assuming a nucleophilic ring
opening by hydride addition at the less-substituted carbon, the reaction corresponds to
the Markovnikov orientation. This reaction sequence is therefore an alternative to the
hydration methods discussed in Chapter 4 for converting alkenes to alcohols.

130 S. Krishnamurthy, R. M. Schubert, and H. C. Brown, J. Am. Chem. Soc., 95, 8486 (1973).
131
H. C. Brown, S. Ikegami, and J. H. Kawakami, J. Org. Chem., 35, 3243 (1970).
132
J. J. Eisch, Z.-R. Liu, and M. Singh, J. Org. Chem., 57, 1618 (1992).
133 D. J. Pasto, C. C. Cumbo, and J. Hickman, J. Am. Chem. Soc., 88, 2201 (1966).
134
H. C. Brown and N. M. Yoon, J. Am. Chem. Soc., 90, 2686 (1968).