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A bicyclic amidine commonly used as a relatively non-nucleophilic organic base. Its conjugate acid is stabilized by charge delocalization.

One equivalent supplies carbon; the other acts as a base for the product. The newly formed 1,3-diketone is appreciably more acidic than the ketone from which D was prepared. proton transfer from its central CH2 to a second enolate equivalent is therefore favourable. Product-enolate stabilization also helps drive the acyl-substitution sequence towards completion.

The second enolate is consequently consumed as base, yielding pinacolone, rather than supplying a second carbon fragment to E. acid workup reverses the product deprotonation. Ignoring this acid–base step would predict that a single equivalent of D is sufficient to consume every equivalent of acyl chloride, despite the product immediately quenching part of the available reagent.

The five-carbon unit is initially an open chain, not a completed carbocycle. Label it $P_1-P_2-P_3-P_4-P_5$, with phenyl-bearing $P_1$, carbonyl $P_3$, amide-substituted $P_4$, and the two ethylthio groups on $P_5$. Its double bonds are initially $P_1=P_2$ and $P_4=P_5$. Let $X$ be the nitro-bearing carbon of nitroethane; its methyl remains a substituent throughout.

DBU removes an alpha proton from nitroethane to give a nitronate. carbon attack at the Michael acceptor $P_1$ forms $X-P_1$, with electron redistribution through $P_2-P_3$ onto the carbonyl oxygen. proton transfer restores the ketone. Removing the remaining X–H proton gives another carbon-nucleophilic nitronate. It attacks the other conjugated end, $P_5$, intramolecularly, closing the six-membered circuit $P_1-P_2-P_3-P_4-P_5-X$. Addition to the ketene dithioacetal and ethylthiolate elimination restore the $P_4=P_5$ bond, leaving one SEt group at $P_5$.

base-assisted loss of the proton at $P_1$, with C–NO2 cleavage at X, creates $P_1=X$ and expels nitrite. Enolization at $P_2-P_3$ supplies the third aromatic double bond and the phenolic OH. proton transfers to the leaving anions complete the acid–base balance. nitroethane supplies the new ring carbon X and its methyl substituent; its nitro group is eliminated. Aromatization, rather than a separate oxidation of an intact six-membered starting ring, provides the final driving force. This is a proposed stepwise nitroalkane benzannulation; related DBU-promoted tandem Michael addition/cyclization/aromatization has direct primary precedent.^[ref]

The new bridge is made by an intramolecular Michael addition. On the cyclohexanone side, the methyl-bearing fused alpha carbon is quaternary and cannot be deprotonated there. triethylamine can instead generate a small equilibrium population of the enolate at the other, methylene alpha carbon. Its carbon attacks the beta carbon of the enone in the seven-membered ring. The enone pi electrons move towards its carbonyl and then onto oxygen, creating the new bridge and a second enolate.

protonation of that enolate at the former methyl-substituted enone alpha carbon restores the left-hand ketone. The initial enone C=C has therefore become a saturated C–C bond while one new transannular C–C bond forms. Both ketones are retained, and the initial two-ring framework becomes a three-ring framework without changing the total index of hydrogen deficiency. The methyl originally at the fused quaternary centre does not migrate; the other methyl ends up on a protonated, formerly unsaturated carbon. A strong-base concentration large enough for quantitative enolate generation is unnecessary for a favourable intramolecular trapping reaction, and neither an aldol dehydration nor a methyl shift is needed.

Number the OH-bearing carbon C1 and the adjacent brominated carbon C2. In the trans bromohydrin, base generates an alkoxide. A chair conformation can place O at C1 and Br at C2 trans-diaxial, aligning the oxygen nucleophile for backside attack at C2. Intramolecular SN2 closure expels bromide and inverts C2: the retained C1–O bond and the newly formed C2–O bond are both on the original OH face, giving the epoxide shown. ring inversion can provide the reactive chair even if it is not the dominant ground-state conformer.

The cis bromohydrin cannot place OH and Br trans-diaxial: one is axial when the other is equatorial. In the chair with Br axial, the hydrogen on C1 can instead be antiperiplanar to C2–Br. An alkoxide-assisted semipinacol pathway moves the C1–H bonding pair to C2 while the oxygen lone pair forms C1=O and bromide departs. hydride migration gives the ketone without changing the carbon skeleton. The hydrogen is transferred to C2 rather than expelled as a free hydride. The original phenyl-bearing stereocentre is not involved in either bond-reorganization sequence. Configuration controls which properly aligned displacement or migration can occur; a flat ring drawing alone conceals that distinction.

triethylamine removes an alpha proton from nitromethane to generate a nitronate population. Its carbon attacks the cyclic ketone carbonyl of E, forming a new C–CH2NO2 bond while the C=O pi pair moves onto oxygen. protonation by triethylammonium or another proton donor gives the tertiary alcohol F and regenerates base. This is a Henry reaction, also called a nitroaldol reaction: the former ketone carbon now bears both OH and CH2NO2.

The nitro group remains attached to its original nitromethane carbon; attack through oxygen would give a different connectivity. The methyl acetal and the original alcohol substituents need not be cleaved or displaced. This addition produces the isolated connectivity without requiring dehydration to a nitroalkene. The stated complex mixture is compatible with competing additions or stereoisomers, but the scheme supplies no basis for claiming F is the unique or kinetically dominant product. Only its formation is being explained.

The first base equivalent removes O–H; the second removes the alpha C–H. The first equivalent of lithium diisopropylamide converts the carboxylic acid to its lithium carboxylate. A further equivalent removes the remaining hydrogen on the carbon between the two allyl groups, giving a carboxylic acid dianion:The second negative charge has enolate-like delocalization into the carboxyl group; lithium coordination and aggregation are not represented by this simple charge-bookkeeping structure. The carbon nucleophile attacks methyl iodide with C–I bond cleavage, forming the new C–Me bond. acid workup reprotonates the carboxylate, giving $F=\mathrm{H}{\mathrm{O}}_2\mathrm{C}-\mathrm{C}(\mathrm{Me})(\mathrm{L}{)}_2$. The two equivalents are therefore chemically necessary for the stated carbon alkylation rather than simply an arbitrary excess. A single equivalent is consumed predominantly by the much more acidic carboxylic proton. The product has formula ${\mathrm{C}}_9{\mathrm{H}}_{14}{\mathrm{O}}_2$ and still has two identical allyl groups, so this methylation does not create a stereocenter.

hydroxide attacks an ester carbonyl to form a tetrahedral intermediate. Collapse expels ethoxide, and acid–base transfer gives the carboxylate and ethanol. Repeating this nucleophilic acyl substitution at the other ester produces the malonate dianion; acid workup gives $\mathrm{H}{\mathrm{O}}_2\mathrm{C}-\mathrm{C}(\mathrm{L}{)}_2-\mathrm{C}{\mathrm{O}}_2\mathrm{H}$, with $L=\mathrm{C}{\mathrm{H}}_2\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$ as defined above.

On heating, one carboxylic acid group is lost through a six-membered cyclic proton-transfer/bond-cleavage arrangement. A carbonyl oxygen of the retained group accepts the proton from the departing carboxyl OH as its C–C bond breaks and carbon dioxide forms; electron redistribution gives the enol-like form of the retained acid. proton transfer/tautomerization then producesThe net decarboxylation is ${\mathrm{C}}_9{\mathrm{H}}_{12}{\mathrm{O}}_4\to {\mathrm{C}}_8{\mathrm{H}}_{12}{\mathrm{O}}_2+\mathrm{C}{\mathrm{O}}_2$. The central carbon gains a hydrogen, both allyl substituents survive, and only one carboxyl group is removed. It would be incorrect to draw hydrolysis directly giving the final acid without accounting for this carbon loss. The favourable cyclic pathway is characteristic of malonic acid decarboxylation.

The malonate carbon receives two allyl groups. With $L=\mathrm{C}{\mathrm{H}}_2\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$, attached through its first carbon, the product issodium hydride removes a methylene proton from diethyl malonate; molecular hydrogen formation accompanies production of an enolate stabilized by resonance in chemistry. Its carbon attacks the bromomethylene carbon of allyl bromide in an SN2 reaction, expelling bromide. The monoalkylated malonate still has one hydrogen between the carbonyls. Excess base removes that hydrogen, and a second equivalent of allyl bromide produces a second carbon–carbon bond. The final malonate carbon has no remaining hydrogen and cannot undergo a third analogous deprotonation there.

The two alkenes are preserved because the substitution occurs at the primary carbon bearing bromine. Counting the introduced groups gives ${\mathrm{C}}_{13}{\mathrm{H}}_{20}{\mathrm{O}}_4$ for the diallylated diethyl ester. Its two identical allyl groups also mean that the central carbon is not a stereocenter. This stage is the alkylation portion of the malonic ester synthesis.

base removes an alpha-amide proton from G, giving a carbon nucleophile. Its intramolecular attack on the nitroaryl ipso carbon, which currently bears the ether oxygen, forms a five-membered cyclic Meisenheimer complex. Count its atoms along the existing tether: alpha carbon, the original phenyl carbon bearing the side chain, its adjacent phenoxy carbon, ether oxygen, and attacked nitroaryl ipso carbon. The ortho nitro group again stabilizes the temporarily dearomatized anion.

Rearomatization now breaks the nitroaryl–O bond, leaving phenoxide on the original ring. proton transfer gives $(2-\mathrm{HO}{\mathrm{C}}_6{\mathrm{H}}_4)-\mathrm{CH}(2-\mathrm{N}{\mathrm{O}}_2{\mathrm{C}}_6{\mathrm{H}}_4)-\mathrm{C}(=\mathrm{O}){\mathrm{N}}_{\mathrm{morph}}$. This is a Truce-Smiles rearrangement: the nitroaryl group migrates from oxygen to carbon, while the original phenoxy oxygen stays on its original ring and becomes OH. No nitro-group migration or amide cleavage is needed. G and H have identical formulas; only the bond connections and a proton position change. carbonate need not produce a high equilibrium enolate concentration: a small population can be consumed by favourable intramolecular cyclization and rearomatization. The specified transformation alone does not establish its detailed proton-transfer sequence.

With triethylamine present, proton transfer from thiophenol produces a more nucleophilic thiolate population. sulfur attacks the anomeric epoxide carbon C1 from the face opposite its epoxide C–O bond. Displacement by backside attack opens the epoxide, breaks C1–O, and leaves the former epoxide oxygen attached to C2. protonation of that alkoxide by thiophenol or triethylammonium gives G: SPh at C1 on the front face and OH at C2 on the back face, a trans relationship. This is inversion at C1 with retention of the C2 C–O bond; there is no need to invert every stereocentre. Rapid protonation also suppresses competing silyl transfer by the alkoxide.

Without added base, neutral thiophenol is less nucleophilic. acid-assisted cleavage at the anomeric epoxide bond can instead be accompanied by donation from the ring oxygen, giving an oxocarbenium ion with charge shared with the ring oxygen. thiophenol capture from the face that puts SPh back on the original epoxide face, followed by deprotonation, gives H with SPh and C2–OH both on the back face, the net-retention pathway. An ion-pair or highly asynchronous opening can provide this outcome; the drawing does not establish a long-lived free carbocation.

The distinction is configuration, not a mandatory fixed chair. For the closely matching trisilylated substrate, the primary study obtained both anomers with thiophenol alone, and established an unusual inverted chair for the alpha thioglycoside by NMR and crystallography. Thus H should be explained as an accessible product, not asserted to be the sole product or necessarily to have axial SPh in its preferred conformation.^[ref]