bulnesol is a key ingredient of oil of guaiac, a fragrance.
ratcliffe, heathcock, j. am. chem. soc. 1971, 93, 1746
(2 points each) fill in the missing reagents for the synthesis of bulnesol.

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Accepted Answer

{ "quality": "clear", "question_count": 10, "skills_matched": [ "step_cot", "table_formatter", "explain_then_answer", "tutor", "mastery_adaptive_brevity" ], "needs_drawing": false, "concepts_used": [ "Carbonyl Reduction", "Esterification" ], "new_concepts": [ "Acetal Protection", "Ether Synthesis", "Tosylation" ], "current_concepts": [ "Carbonyl Reduction", "Esterification", "Acetal Protection", "Ether Synthesis", "Tosylation" ] } ## Reduce the non-conjugated ketone Using the *Carbonyl Reduction* knowledge point $$ \text{Reagents: } \text{NaBH}_4, \text{MeOH} $$ ## Acetylate the secondary alcohol Using the *Esterification* knowledge point $$ \text{Reagents: } \text{Ac}_2\text{O}, \text{py} \quad (\text{or } \text{AcCl}, \text{py}) $$ ## Protect the conjugated ketone The conjugated ketone is selectively protected as a cyclic acetal (ketal) using ethylene glycol in the presence of an acid catalyst: $$ \text{Reagents: } \text{HOCH}_2\text{CH}_2\text{OH}, \text{TsOH} $$ ## Reduce the ester group The acetate ester ($-\text{OAc}$) is selectively reduced to a secondary alcohol using a strong reducing agent: $$ \text{Reagents: } \text{LiAlH}_4, \text{then } \text{H}_3\text{O}^+ $$ ## Alkylate the secondary alcohol The secondary alcohol is converted to a benzyl ether ($-\text{OBn}$) via deprotonation followed by nucleophilic substitution: $$ \text{Reagents: } 1.\ \text{NaH}, \ 2.\ \text{BnBr} $$ ## Deprotect the acetal group The cyclic acetal protecting group is hydrolyzed back to the ketone under aqueous acidic conditions: $$ \text{Reagents: } \text{H}_3\text{O}^+ \quad (\text{or } \text{HCl}, \text{H}_2\text{O}) $$ ## Reduce the double bond The carbon-carbon double bond is selectively hydrogenated to a single bond using hydrogen gas over a transition metal catalyst: $$ \text{Reagents: } \text{H}_2, \text{Pd/C} $$ ## Convert alcohol to a tosylate The secondary alcohol is converted into a good leaving group (tosylate, $-\text{OTs}$) using p-toluenesulfonyl chloride: $$ \text{Reagents: } \text{TsCl}, \text{pyridine} $$ | Box | Reaction Step / Transformation | Missing Reagents | | :--- | :--- | :--- | | 1 | Reduction of non-conjugated ketone | $\text{NaBH}_4, \text{MeOH}$ | | 2 | Acetylation of secondary alcohol | $\text{Ac}_2\text{O}, \text{pyridine}$ | | 3 | Acetal protection of conjugated ketone | $\text{HOCH}_2\text{CH}_2\text{OH}, \text{TsOH}$ | | 4 | Reduction of acetate ester to alcohol | $\text{LiAlH}_4$, then $\text{H}_3\text{O}^+$ | | 5 | Benzylation of secondary alcohol | $1.\ \text{NaH},\ 2.\ \text{BnBr}$ | | 6 | Hydrolysis of acetal to ketone | $\text{H}_3\text{O}^+$ | | 7 | Hydrogenation of alkene | $\text{H}_2, \text{Pd/C}$ | | 8 | Tosylation of secondary alcohol | $\text{TsCl}, \text{pyridine}$ | { "subject": "Natural Science", "question_type": "Fill-in-the-blank", "knowledge_point": [ "Natural Science", "Chemistry", "Organic Synthesis" ] }

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Question

Explanation:

Reduce the non-conjugated ketone

Acetylate the secondary alcohol

Protect the conjugated ketone

Reduce the ester group

Alkylate the secondary alcohol

Deprotect the acetal group

Reduce the double bond

Convert alcohol to a tosylate

Answer:

Box	Reaction Step / Transformation	Missing Reagents
2	Acetylation of secondary alcohol	\(\text{Ac}_2\text{O}, \text{pyridine}\)
3	Acetal protection of conjugated ketone	\(\text{HOCH}_2\text{CH}_2\text{OH}, \text{TsOH}\)
4	Reduction of acetate ester to alcohol	\(\text{LiAlH}_4\), then \(\text{H}_3\text{O}^+\)
5	Benzylation of secondary alcohol	\(1.\ \text{NaH},\ 2.\ \text{BnBr}\)
6	Hydrolysis of acetal to ketone	\(\text{H}_3\text{O}^+\)
7	Hydrogenation of alkene	\(\text{H}_2, \text{Pd/C}\)
8	Tosylation of secondary alcohol	\(\text{TsCl}, \text{pyridine}\)