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Reinforced Reasoning for End-to-End Retrosynthetic Planning

arXiv 2603.29723 ↗First posted 31 Mar 2026cs.AIcited by 0

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Abstract (arXiv)

Retrosynthetic planning is a fundamental task in organic chemistry, yet remains challenging due to its combinatorial complexity. To address this, conventional approaches typically rely on hybrid frameworks that combine single-step predictions with external search heuristics, inevitably fracturing the logical coherence between local molecular transformations and global planning objectives. To bridge this gap and embed sophisticated strategic foresight directly into the model's chemical reasoning, we introduce ReTriP, an end-to-end generative framework that reformulates retrosynthesis as a direct Chain-of-Thought reasoning task. We establish a path-coherent molecular representation and employ a progressive training curriculum that transitions from reasoning distillation to reinforcement learning with verifiable rewards, effectively aligning stepwise generation with practical route utility. Empirical evaluation on RetroBench demonstrates that ReTriP achieves state-of-the-art performance, exhibiting superior robustness in long-horizon planning compared to hybrid baselines.

Key facts. No citing papers in the map yet (data through 14 Oct 2026). Builds on 51 of its 91 references that are in the map. First posted on arXiv 31 Mar 2026.

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51 of 91 references.

References · 51

  1. 2022Training language models to follow instructions with human feedbackcited by 15,971
  2. 2023Llama 2: Open Foundation and Fine-Tuned Chat Modelscited by 13,028
  3. 2024DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Modelscited by 9,379
  4. 2025Qwen3 Technical Reportcited by 8,820
  5. 2025DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learningcited by 6,330
  6. 2022Self-Consistency Improves Chain of Thought Reasoning in Language Modelscited by 5,708
  7. 2025DAPO: An Open-Source LLM Reinforcement Learning System at Scalecited by 2,810
  8. 2023Distilling Step-by-Step! Outperforming Larger Language Models with Less Training Data and Smaller Model Sizescited by 737
  9. 2023ChemCrow: Augmenting large-language models with chemistry toolscited by 631
  10. 2020ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Predictioncited by 337
  11. 2023On the Planning Abilities of Large Language Models : A Critical Investigationcited by 312
  12. 2025Reinforcement Learning with Verifiable Rewards Implicitly Incentivizes Correct Reasoning in Base LLMscited by 289
38 more
  1. 2018Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Predictioncited by 229
  2. 2021Large-Scale Chemical Language Representations Capture Molecular Structure and Propertiescited by 206
  3. 2017Learning to Plan Chemical Synthesescited by 179
  4. 2022Translation between Molecules and Natural Languagecited by 177
  5. 2025Thinkless: LLM Learns When to Thinkcited by 113
  6. 2024ChemLLM: A Chemical Large Language Modelcited by 106
  7. 2020Retrosynthesis Prediction with Conditional Graph Logic Networkcited by 104
  8. 2020Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Editscited by 88
  9. 2017Retrosynthetic reaction prediction using neural sequence-to-sequence modelscited by 86
  10. 2020A Graph to Graphs Framework for Retrosynthesis Predictioncited by 86
  11. 2020Retro*: Learning Retrosynthetic Planning with Neural Guided A* Searchcited by 76
  12. 2020The Synthesizability of Molecules Proposed by Generative Modelscited by 68
  13. 2021Permutation invariant graph-to-sequence model for template-free retrosynthesis and reaction predictioncited by 68
  14. 2020Learning Graph Models for Retrosynthesis Predictioncited by 65
  15. 2017SMILES Enumeration as Data Augmentation for Neural Network Modeling of Moleculescited by 59
  16. 2024Developing ChemDFM as a large language foundation model for chemistrycited by 52
  17. 2022Root-aligned SMILES: A Tight Representation for Chemical Reaction Predictioncited by 51
  18. 2020Barking up the right tree: an approach to search over molecule synthesis DAGscited by 31
  19. 2024Multimodal Large Language Models for Inverse Molecular Design with Retrosynthetic Planningcited by 29
  20. 2022RetroGraph: Retrosynthetic Planning with Graph Searchcited by 24
  21. 2024Double-Ended Synthesis Planning with Goal-Constrained Bidirectional Searchcited by 24
  22. 2021Self-Improved Retrosynthetic Planningcited by 23
  23. 2023Retrosynthetic Planning with Dual Value Networkscited by 21
  24. 2025ChemDFM-R: A Chemical Reasoning LLM Enhanced with Atomized Chemical Knowledgecited by 20
  25. 2025Chemical reasoning in LLMs unlocks strategy-aware synthesis planning and reaction mechanism elucidationcited by 17
  26. 2025Chem-R: Learning to Reason as a Chemistcited by 17
  27. 2023Retrosynthesis Prediction with Local Template Retrievalcited by 16
  28. 2022FusionRetro: Molecule Representation Fusion via In-Context Learning for Retrosynthetic Planningcited by 14
  29. 2025LLM-Augmented Chemical Synthesis and Design Decision Programscited by 13
  30. 2025AOT*: Efficient Synthesis Planning via LLM-Empowered AND-OR Tree Searchcited by 13
  31. 2024ALaRM: Align Language Models via Hierarchical Rewards Modelingcited by 11
  32. 2024DirectMultiStep: Direct Route Generation for Multistep Retrosynthesiscited by 11
  33. 2024Automatic Prompt Selection for Large Language Modelscited by 9
  34. 2024Preference Optimization for Molecule Synthesis with Conditional Residual Energy-based Modelscited by 6
  35. 2025TempRe: Template generation for single and direct multi-step retrosynthesiscited by 6
  36. 2025DeepRetro: Retrosynthetic Pathway Discovery using Iterative LLM Reasoningcited by 4
  37. 2025Trustworthy Retrosynthesis: Eliminating Hallucinations with a Diverse Ensemble of Reaction Scorerscited by 4
  38. 2025Atom-anchored LLMs speak Chemistry: A Retrosynthesis Demonstrationcited by 4

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  1. 2026RetroPlanner: Multi-Route Expansion and Multi-Objective Reasoning for LLM-Based Retrosynthesis Planning
  2. 2025RetroDFM-R: Reasoning-Driven Retrosynthesis Prediction with Large Language Models via Reinforcement Learning
  3. 2026RetroReasoner: A Reasoning LLM for Strategic Retrosynthesis Prediction
  4. 2026RetroAgent: Harnessing LLMs to Search Over Structured Memory for Agentic Retrosynthesis Planning
  5. 2026Representation Alignment as a Bottleneck in LLM-Based Retrosynthesis Planning
  6. 2025Synthelite: Chemist-aligned and feasibility-aware synthesis planning with LLMs
  7. 2025LARC: Towards Human-level Constrained Retrosynthesis Planning through an Agentic Framework
  8. 2025RETRO SYNFLOW: Discrete Flow Matching for Accurate and Diverse Single-Step Retrosynthesis