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Disconnect the new bond between the two six-carbon units. One portion of bromocyclohexane supplies a grignard reagent; another supplies cyclohexene oxide:A bulky strong base can favour E2 elimination in the alkene-forming step; a peracid such as meta-chloroperoxybenzoic acid provides epoxidation. None of its carbons enters the target.

Treat cyclohexene oxide with cyclohexylmagnesium bromide, then perform acidic aqueous work-up. Backside attack on one epoxide carbon breaks its C–O bond and installs cyclohexyl opposite the retained oxygen. Protonation of the oxygen gives trans-2-cyclohexylcyclohexan-1-ol, the required relative configuration. The two six-carbon reactant portions supply all 12 target carbons. An achiral synthesis produces a racemic mixture trans pair; obtaining only the particular enantiomer represented by the drawing would require resolution or an enantioselective step. The useful stable chair can place the two large trans-1,2 substituents approximately diequatorial.

D is racemic trans-2-methylcyclohexan-1-ol. E is racemic 1-methyl-2-phenylcyclohexan-1-ol with OH and Ph trans, and Me and Ph cis. Number the starting alkene carbon carrying methyl as ${\mathrm{C}}_1$ and its partner as ${\mathrm{C}}_2$ in the reaction explanation below; the product name of D renumbers the OH-bearing carbon as 1.

For D, hydroboration proceeds through a concerted four-centre transition state: the alkene pi pair donates to boron while B–H supplies the new C–H bond. Boron attaches mainly to less substituted ${\mathrm{C}}_2$ and hydrogen to ${\mathrm{C}}_1$, on the same face. Under peroxide/base conditions, hydroperoxide attacks B; migration of the C–B bond to the adjacent oxygen, with O–O cleavage, replaces C–B by C–O with retention at carbon. Hydrolysis/proton transfer releases the alcohol. Thus the newly added H and OH are syn, making the pre-existing methyl and OH trans. Attack on either alkene face gives the enantiomeric pair.

For E, the peracid transfers its terminal oxygen across the alkene in concerted epoxidation, through cyclic electron flow that also breaks O–O and transfers the acidic proton to the peracid carbonyl oxygen. The resulting epoxide retains the relative configuration of the alkene substituents. The phenyl equivalent from phenylmagnesium bromide then attacks less substituted ${\mathrm{C}}_2$ from the face opposite the epoxide oxygen. Its C–O bond breaks onto oxygen, an SN2-like ring opening; the oxygen stays attached to ${\mathrm{C}}_1$. Water workup protonates that alkoxide. Consequently OH at ${\mathrm{C}}_1$ and Ph at ${\mathrm{C}}_2$ are anti, while the methyl at ${\mathrm{C}}_1$ lies on the same relative face as Ph.

An acetal retrosynthesis separates the target into trans-cyclohexane-1,2-diol and cyclohexyl methyl ketone. Both fragments can be prepared using separate portions of cyclohexene.

For the diol, epoxidation with a peroxy acid such as mCPBA gives cyclohexene oxide. Acid-catalysed opening with water occurs by backside attack on the protonated epoxide, giving the anti, hence trans, diol. A syn dihydroxylation would give the wrong relative configuration.

For the ketone, add HBr to another portion of cyclohexene to obtain bromocyclohexane, form its grignard reagent with Mg in dry ether, and add acetonitrile. Hydrolyse the resulting magnesium imine salt to ${\mathrm{C}}_6{\mathrm{H}}_{11}\mathrm{COMe}$. A nitrile is useful here because addition followed by hydrolysis stops at the ketone instead of giving the double addition associated with an ester.

Finally combine the isolated trans diol and ketone with catalytic acid and remove water to form the cyclic ketal. The ketone carbon becomes the acetal carbon bearing Me and cyclohexyl; the two original diol C–O bonds retain their relative configuration. Anti epoxide opening supplies the required trans relationship before ketal formation. ketal formation is an equilibrium and the trans-fused product may be less favourable than an unstrained acetal, so effective water removal and isolation are necessary; substituting a cis diol is not an acceptable shortcut.

The free allylic hydroxyl can hydrogen-bond to the peracid and accelerate directed oxygen transfer to the nearby double bond. The remote styryl double bond lacks this directing contact. Epoxidation of the hydroxyl-adjacent alkene is therefore favoured, even though both alkenes are in principle oxidizable. Peracid epoxidation is a concerted oxygen transfer: alkene $\pi$ donation to terminal peroxide oxygen, O–O cleavage, proton transfer and carbonyl re-formation occur through a cyclic transition-state arrangement. The alkene's E geometry is retained as a trans relationship between its substituents in the epoxide.

The two alkene faces are diastereotopic because the molecule already contains stereocentres. A plausible substrate-controlled conformation minimizes allylic strain and presents the face opposite the bulky OTBS-bearing part of the chain to the oxidant. Predict epoxide oxygen on the face opposite OTBS, retaining the pre-existing methyl and OTBS configurations. Hydrogen-bond direction, steric approach and conformational population compete; one cannot deduce an exact diastereomeric ratio from the flat drawing alone. The same facial preference has been discussed for this synthetic series.^[ref]

The acetylide attacks the less substituted terminal epoxide carbon by SN2 ring opening. The C–O bond at that carbon breaks, leaving the oxygen attached to the original substituted stereocentre. Protonation gives $\mathrm{BnOC}{\mathrm{H}}_2\mathrm{CH}(\mathrm{OH})\mathrm{C}{\mathrm{H}}_2\mathrm{C}\equiv \mathrm{CMe}$. Dissolving-metal reduction then gives the E alkene and also cleaves the benzyl ether.

Thus H is $\mathrm{HOC}{\mathrm{H}}_2\mathrm{CH}(\mathrm{OH})\mathrm{C}{\mathrm{H}}_2\mathrm{CH}=\mathrm{CHMe}$ with an E double bond, and its original epoxide-derived stereocentre is retained geometrically. No new tetrahedral stereocentre is formed: the attacked epoxide carbon becomes CH${}_2$. The new stereochemical information is the E alkene geometry. Calling its secondary hydroxyl carbon “newly generated” would confuse changing its functional environment with creating a new stereocentre.

Both free primary allylic alcohols undergo Sharpless asymmetric epoxidation. With slightly more than two equivalents of hydroperoxide, the expected fully oxidized product is the diepoxide, with both original C=C bonds converted to epoxides and both primary alcohols retained. The two central pre-existing stereocentres and their ether substituents are retained.

The stereochemical construction is unambiguous by applying the L-(+)-tartrate mnemonic separately at each end: orient that alkene horizontally with its CH${}_2$OH group at lower right, and deliver oxygen from the back face. In the source's original in-plane orientation this gives the left epoxide oxygen behind the plane and the right epoxide oxygen in front. The methyl and hydroxymethyl groups retain their original relative arrangement about each former double bond. One cannot simply draw both oxygens on the same face of the original extended chain: the two allylic-alcohol ends have opposite drawing orientations. titanium binding to each free hydroxyl directs oxygen transfer; the pre-existing stereocentres can create matched/mismatched rate differences, but the stated reagent control predicts the stereochemistry of both epoxidations. Molecular sieves maintain a dry active titanium–tartrate system.^[ref]

The free allylic alcohol directs epoxidation of the adjacent alkene rather than the remote double bond. Applying the D-(−)-tartrate mnemonic gives the epoxide oxygen on the back face in the source orientation, with both new C–O bonds dashed if the original six-membered ring is kept in the plane. The CH${}_2$OH substituent at the lower epoxide carbon consequently projects towards the front in an explicit tetrahedral product drawing. The remote double bond is retained. The opposite tartrate would reverse both newly created epoxide stereocentres; it would not alter the location of the epoxidized alkene.

Number the epoxide-bearing ring carbon carrying CH${}_2$OH as C1, then proceed through the other epoxide carbon C2 around the ring to C6. Heating with water opens the epoxide at the less substituted C2 by backside attack: the incoming oxygen becomes C2–OH on the front face, while the original epoxide oxygen remains as C1–OH on the back face. Proton transfers complete formation of the triol. Thus the two original epoxide oxygens' roles are distinct: one is retained from B and the new hydroxyl oxygen comes from water.

Iodine next activates the remaining C4=C5 bond as an iodonium ion. The pendant primary alcohol oxygen attacks intramolecularly at C5 to make the five-membered cyclic ether with path O–CH${}_2$–C1–C6–C5, opening the iodonium anti and leaving iodine at C4 on the opposite face. Bicarbonate removes the oxonium proton and neutralizes acid; it is not the source of the ether oxygen. The folded tether selects the face of closure compatible with the bridged structure, accounting for the ether/iodine stereochemistry.

The remaining two hydroxyl groups react with acid-activated 2,2-dimethoxypropane. Successive oxygen attack, methanol departure and intramolecular closure form the isopropylidene ketal of C, protecting that diol without changing its carbon configurations. The terminal primary hydroxyl has already become the cyclic ether and is not one of the two acetonide oxygens. This atom tracking distinguishes the epoxide hydrolysis, iodoetherification and protection stages.

${\mathrm{C}}_6{\mathrm{H}}_5\mathrm{MgBr}$, a phenyl-transfer reagent that can open an epoxide by attack at carbon.