Stereochemistry of Substitution Products: 04-BS-12, December 2018, Q4

Question 4: Stereochemistry of Substitution Products (equal value)

Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.

a) Pentyl tosylate is a primary substrate; ^–CN is a strong, unhindered nucleophile, so this is a clean S_N2. The reacting carbon is primary (two H's, no stereocentre either before or after), so the product carries no stereochemical label.

pentyl tosylate

hexanenitrile (S_N2, no stereocentre)

b) Propyl tosylate (primary) reacting with potassium tert-butoxide (a very bulky, strongly basic alkoxide) is the one classic exception to "strong nucleophile means S_N2 wins": tert-butoxide is so sterically hindered around its own oxygen that it cannot act as an effective S_N2 nucleophile even on a primary carbon, and instead acts as a bulky base, giving E2 elimination to propene rather than substitution. There is no stereocentre in either the substrate or the alkene product.

propyl tosylate

propene (E2 elimination — bulky K^+–OC(CH₃)₃ acts as a base, not a nucleophile, here)

c) This is the one genuine stereocentre in the question. The starting tosylate is drawn with OTs on a bold wedge and H on a hashed dash at the stereocentre, with CH₃ and the propyl chain (CH₂CH₂CH₃) in the plane. Assigning CIP priority (OTs > propyl > CH₃ > H) with H already pointing away from the viewer (it is on the dash) and reading OTs→propyl→CH₃ traces a clockwise path — the starting material is (R)-pentan-2-yl tosylate.

(R)-pentan-2-yl tosylate, the Question 4c substrate

^–SH is a strong, small, unhindered nucleophile attacking a secondary carbon: S_N2, backside attack, clean inversion of the spatial arrangement at that one carbon. In the product, sulfur (atomic number 16) still outranks every other substituent on that carbon just as oxygen did in the tosylate, so the CIP priority order is unchanged in rank even though the atom changed — the spatial inversion therefore shows up directly as a flipped descriptor: the product is (S)-pentane-2-thiol.

(S)-pentane-2-thiol — inverted at the stereocentre (S_N2)

Topic: Stereochemical outcome of substitution/elimination at a single stereocentre.

Key relations: S_N2 ⇒ inversion (backside attack); a bulky alkoxide (tert-butoxide) is a base, not an S_N2 nucleophile, even on a primary carbon; whether inversion flips the R/S label depends on whether the incoming and leaving groups keep the same CIP priority rank.

Why this works: the nucleophile must approach 180° from the leaving group in S_N2, which necessarily inverts the three-dimensional arrangement of the other three groups; the R/S label is a separate bookkeeping step layered on top of that physical fact.

Common pitfall: assuming "inversion" always means "R becomes S" — that is only true when the incoming group keeps the same priority rank as the outgoing one (as it does here, O→S, both rank 1); if the ranks swapped, the same physical inversion could leave the label unchanged.

Source: McMurry, Organic Chemistry, 9th ed., Ch. 11 (S_N2 stereochemistry) & Ch. 9 (CIP rules).

Question 4 of 13: Stereochemistry of Substitution Products

Question 4: Stereochemistry of Substitution Products (equal value)