Q7(c). Reagents: NaBH₄, LiAlH₄, Birch, SeO₂, Pb(OAc)₄

Introduction. Five reagents chosen for selectivity: a mild hydride that leaves esters alone, a hydride whose stereochemistry is set by a conformationally locked ring, a dissolving-metal reduction of an arene, an allylic oxidation, and an oxidation of a hydroquinone.

(i) NaBH₄: aldehyde reduced, ester kept

BH₄⁻ transfers hydride to the more electrophilic aldehyde C=O; ethanol protonates the alkoxide. The ester carbonyl is stabilised by the lone pair of OMe and reacts far more slowly. Product: methyl 3-(hydroxymethyl)benzoate.

Scheme: Chemoselective reduction.

(ii) LiAlH₄ on 4-tert-butylcyclohexanone

The tert-butyl group is fixed equatorial and locks the chair. Small AlH₄⁻ attacks from the axial direction (torsional strain with the axial H atoms on C-2 and C-6 is smaller along this path), so the new OH is equatorial. Product: trans-4-tert-butylcyclohexan-1-ol (about 90 %), with about 10 % of the cis (axial OH) isomer. (Bulky L-Selectride attacks equatorially and gives mainly the cis alcohol.)

Scheme: Small hydrides give the thermodynamically favoured equatorial alcohol.

(iii) Birch reduction of anisole

1. Na gives an electron to the ring (solvated electron in NH₃): radical anion.
2. Ethanol protonates it ortho to OMe; for an electron donor the negative charge avoids the carbon bearing OMe.
3. A second electron and a second proton give the non-conjugated diene; the OMe ends on a C=C.

Product: 1-methoxycyclohexa-1,4-diene (acid hydrolysis would give cyclohex-2-enone/cyclohex-3-enone).

Scheme: Electron-donating groups end on an unreduced C=C.

(iv) SeO₂ allylic oxidation

1. Ene reaction: SeO₂ (Se=O as the enophile) takes an allylic H from the methyl group trans to R and forms an allylic seleninic acid, with the C=C moved.
2. A [2,3]-sigmatropic rearrangement moves the C=C back and gives an allylic seleninate ester.
3. Hydrolysis gives the allylic alcohol; further oxidation can give the aldehyde.

The oxidised carbon is the methyl trans to the larger group R (Bhalla–Sharpless rule), so the geometry is (E). Product: (E)-2-methyl-3-R-prop-2-en-1-ol, R-CH=C(CH₃)-CH₂OH (with some (E)-enal).

Scheme: The CH₃ trans to R becomes CH₂OH.

(v) Pb(OAc)₄ on 2-cyanohydroquinone

Lead tetra-acetate is a two-electron oxidant. One phenolic OH exchanges with an acetate on lead (ArO-Pb(OAc)₃); the O–Pb bond breaks heterolytically with loss of Pb(OAc)₂ and AcO⁻, and the second OH loses H⁺. The para-dihydroxy compound is oxidised to the para-quinone. Product: 2-cyano-1,4-benzoquinone (2-cyanocyclohexa-2,5-diene-1,4-dione).

Scheme: Hydroquinone to quinone: the electron-poor cyanoquinone is a strong dienophile and oxidant.

Conclusion. (i) Methyl 3-(hydroxymethyl)benzoate; (ii) trans-4-tert-butylcyclohexanol; (iii) 1-methoxycyclohexa-1,4-diene; (iv) the (E)-allylic alcohol RCH=C(CH₃)CH₂OH; (v) 2-cyano-1,4-benzoquinone.

Application. Birch reduction of anisoles is the key step in making 19-norsteroid oral contraceptives; SeO₂ allylic oxidation is used in terpene and vitamin synthesis; cyanoquinones (like DDQ) are dehydrogenating oxidants.