Q3(a). trans- and cis-2-Bromocyclopentanol with hydroxide

Introduction. Hydroxide first removes the O–H proton (fast acid–base step). What the alkoxide can do next depends on the geometry. An intramolecular SN2 needs the O⁻ to reach the back of the C–Br bond, i.e. O and Br anti-periplanar; this is possible only in the trans isomer. In the cis isomer the O⁻ lies on the same face as Br, so the external OH⁻ does the back-side attack instead.

(i) trans isomer: neighbouring-group participation gives the epoxide

Scheme: The alkoxide is a built-in nucleophile on the face opposite to Br.

1. OH⁻ deprotonates the OH: R-OH + OH⁻ ⇌ R-O⁻ + H₂O.
2. In the trans compound the O⁻ on C-1 and Br on C-2 are on opposite faces; in the half-chair (envelope) conformer they are anti-periplanar. The alkoxide attacks C-2 from the back, and Br⁻ leaves (an intramolecular Williamson ether synthesis, rate ∝ [bromohydrin][OH⁻]).
3. The three-membered ring closes with inversion at C-2. Because it is intramolecular (high effective concentration), it is much faster than attack by external OH⁻: the product is cyclopentene oxide (6-oxabicyclo[3.1.0]hexane), a cis-fused meso epoxide.

(ii) cis isomer: direct SN2 by hydroxide

Scheme: Attack from the face opposite to Br puts the new OH trans to the old one.

1. The alkoxide of the cis isomer is on the same face as Br; it cannot reach the back of C–Br, so no epoxide can form.
2. External OH⁻ attacks C-2 from the face opposite to Br (bimolecular SN2, slower). The configuration at C-2 is inverted: the new OH ends up on the face opposite to the C-1 OH.
3. The product is trans-cyclopentane-1,2-diol (racemic, R,R + S,S).

Check through the epoxide. The same trans-diol is formed if the epoxide of (i) is opened by OH⁻ (back-side attack on one carbon): epoxide opening and direct SN2 on the cis bromohydrin both deliver anti stereochemistry. Hence (i) at higher temperature and longer time also ends at the trans-diol.

Conclusion. (i) The trans-bromohydrin forms an alkoxide anti-periplanar to Br and closes to cyclopentene oxide by intramolecular SN2. (ii) The cis isomer cannot do so; OH⁻ displaces Br with inversion and gives trans-cyclopentane-1,2-diol. Both results show the back-side (anti) requirement of SN2.

Application. Halohydrin ring closure is the industrial chlorohydrin route to propylene oxide and epichlorohydrin, and the anti-periplanar rule is used to predict which steroid halohydrins give epoxides.