Novel Ambergris Odorants Devoid of Ketal Functions: Sustainable Synthesis of 4‐(α‐Cedren‐8‐yl)Butan‐2‐Ones and Potent Methoxy Derivatives by Claisen Chemistry**

Challenging the importance of the ketal functionality in ambergris odorants, the optionally α‐methoxy substituted ketones 18–20 are designed using an olfactophore model and synthesized by Claisen chemistry from β‐cedren‐9α‐ol (25) as a sustainable starting material with methoxy acetone (15) and acetone dimethyl ketal (29) as synthetic building blocks. Elimination of one alkoxy group with phosphoric acid in pyridine furnished vinyl ethers to which β‐cedren‐9α‐ol (25) is added in the presence of acetic acid. Thermal Claisen rearrangement of the resulting adducts then provides the target compound 18–20 that possesses potent dry woody‐ambery odors with musky aspects that make them ideally suited for oud accords. Surprisingly, the α‐methoxy substituted ketones 18 and 19 are also formed in the synthesis of the new odorant Ambronova, where they contribute to a more musky‐soft, sensual‐animalic character compared to Ambrocenide (1) with additional peppery accents. The content of the desirable 3‐methoxy ketone 19 could be increased by using 1,2,2‐trimethoxypropane (21), thereby finetuning the Ambronova quality. These results show that a ketal functionality is no longer an indispensable prerequisite for an ambergris odorant, which should facilitate the design of further high‐impact ambergris odorants devoid of ketal functionalities with potentially enhanced biodegradability.