IChO-2025_2.1
Type: Structure Construction
Points: 12
Question: context: The major stereoisomer C is formed from the chromium-mediated coupling reaction of aldehyde A and vinyl iodide B and can be predicted using the Felkin-Anh model without chelation. Draw a Newman projection showing the best approach of the nucleophile in this reaction. Use the labels  =O, -H, -R^{1}, -OMe,and Nu. Draw the full structure of the major diastereomer C showing all stereochemistry.
parsing_note: The reaction diagram has been converted to reaction_scheme.
requirement: Draw a Newman projection showing the best approach of the nucleophile in this reaction. Use the labels =O, –H, –R¹, –OMe, and Nu. The projection should be viewed along the C(α)-C(carbonyl) bond. Draw the structure of compound C formed in the Nozaki-Hiyama-Kishi coupling reaction. Show all stereochemistry clearly, particularly at the newly formed chiral centers.
reaction_scheme: reactant_name: A, B
reactant_formula: C=C[C@@H](C)C[C@@H](C)[C@@H](OCC1=CC=C(OC)C=C1)[C@H](OC)C([H])=O, I/C(C)=C/[C@@H](C)[C@@H](OCC1=CC=C(OC)C=C1)CCO[Si](C)(C)C(C)(C)C
conditions: CrCl_{2}, NiCl_{2} (cat.)
product_name: C, C'
product_formula: C_{41}H_{66}O_{7}Si
product_ratio: 2:1
reactant_name: C
conditions: multiple steps
product_name: D + E
product_formula: [R2]CC([H])=O, O=C1O[C@@H](C2=CC=CC=C2)[C@@H](C)N1C(CC[C@@H]3CC[C@@H](O[Si](C)(C)C(C)(C)C)[C@H](C)C3)=O
reactant_name: D + E
reactant_formula: [R2]CC([H])=O, O=C1O[C@@H](C2=CC=CC=C2)[C@@H](C)N1C(CC[C@@H]3CC[C@@H](O[Si](C)(C)C(C)(C)C)[C@H](C)C3)=O
conditions: nBu_{2}BOTf, Et_{3}N
product_name: F
reactant_name: F
conditions: multiple steps
product_name: rapamycin
product_formula: C[C@@H]1CCC2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)O)C)/C)O)OC)C)C)/C)OC
Answer: projection_type: Newman projection
viewing_direction: along C(α)-C(carbonyl) bond
front_carbon: substituents: R^{1}
H
OMe
back_carbon: substituents: =O
H
attacking group (Nu)
nucleophile_approach: direction: from bottom-right
angle_to_carbonyl: ~107°
anti_to: R^{1}
explanation: Nucleophile approaches anti to the largest group (R¹) following Felkin-Anh model
grading: partial_credit: condition: If nucleophile approach not shown or incorrect
deduction: -2
condition: If chirality at rear carbon is wrong, but OMe placed perpendicular
deduction: -4
condition: If chirality at rear carbon is correct, but OMe not placed perpendicular
deduction: -4
notes: Need to use Felkin-Anh model without chelation and put electronegative group OMe perpendicular to aldehyde.
points: 8
name: C and C'
C_smiles: C=C[C@@H](C)C[C@@H](C)[C@@H](OCC1=CC=C(OC)C=C1)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)[C@@H](OCC2=CC=C(OC)C=C2)CCO[Si](C)(C)C(C)(C)C
C'_smiles: C=C[C@@H](C)C[C@@H](C)[C@@H](OCC1=CC=C(OC)C=C1)[C@H](OC)[C@@H](O)/C(C)=C/[C@@H](C)[C@@H](OCC2=CC=C(OC)C=C2)CCO[Si](C)(C)C(C)(C)C
points: 4
grading: full_credit: condition: Structure of C fully correct
partial_credit: condition: If C' is given instead of C
condition: Absolute stereochemistry of OH and OMe is correct
additional_note: If incorrect, but the relative stereochemistry is correct
additional_points: 1
condition: For each error in each molecule in functional groups not undergoing reaction
deduction: -1
notes: No error carried forward awarded even if part a is incorrect as stereochemistry can be inferred from the final structure of rapamycin. PMBO refers to para-methoxybenzyl ether protecting group, OPMB refers to para-methoxybenzyl group, OTBS refers to tert-butyldimethylsilyl ether protecting group.