A Remarkable Ring Contraction En Route to the Chartelline Alkaloids

Abstract

One‐of‐a‐kind. A bromine‐induced rearrangement has been designed for the formation of the spiro‐β‐lactam ring present in the structurally unique chartelline alkaloids (see picture of chartelline A). This method is used in combination with others to provide rapid access to the carbocyclic skeletons of the chartelline, securine, and securamine alkaloids.

Synthesis of Spiroheterocycles by Palladium‐Catalyzed Domino Cycloisomerization/Cross‐Coupling of α‐Allenols and Baylis–Hillman Acetates

“…Pleasingly, a-allenols 1 c and 1 d reacted with BH acetates 2 a and 2 b to furnish selectively the desired spiroazetidinones 6 a-d in moderate to good yields (Scheme 3). [8,9] When a-allenol 1 c and BH acetate containing nitrile 2 c were subjected to this Pd II -catalyzed protocol, the reaction did not yield the expected adduct 6 e, which would have arisen by S N 2 substitution by attack at the methylenic position remote from the leaving group, followed by migration of the double bond. Interestingly, under the present conditions the reaction exclusively led to the spiroazetidinone 7, probably by way of a regio-and diastereospecific S N 1 substitution (Scheme 4).…”

Synthesis and reactivity of spiro-fused β-lactams

“…Baran's approach to synthesise chartelline started from a simple -amino ester 88, which was transformed into a complex amide 89 through a number of steps. 49 The bromination of the latter amide 89 with N-bromosuccinimide, followed by intramolecular cyclisation of the resulting-bromo amide 90, led to the formation of spiro-fused 2-azetidinone 91 (Scheme 29).…”

Studies towards the synthesis of the marine alkaloid chartelline C

“…[1][2][3] A related bryozoan Securiflustra securifrons also produces the securines and securamines, 4,5 and they are plausible biogenetic precursors to the chartellines. It was reported that solutions of securine B 1 in DMSO-d 6 converted into securamine B 2, presumably via 1a , Scheme 1. 4 Redissolving 2 in CDCl 3 converted 2 back into 1.…”

“…The transformation of 1c into 3 can be written as a [1,5]-shift and is a key step in the recently reported biogenetically inspired strategy for the synthesis of 3 by Baran and Shenvi. 6,7 Several other groups have reported on synthetic approaches to chartelline C 6,[8][9][10][11] as well as related alkaloids. 12,13 Our plan was also based on the supposition that the spiro-β-lactam in 3 could arise from a late stage oxidative cyclization of a suitable macrolactam.…”

“…22 Unfortunately, attempts to couple 5 and 16 to give 17, under a variety of Sonogashira and Castro-Stephens reaction conditions failed, Scheme 4. In light of Baran's reported work 6,7 we revisited this reaction applying their reaction conditions, but no coupling product 17 was observed. Presumably, the more reactive 2-iodo analog of 5 would have been successful.…”