Enantioselective Total Synthesis of (−)‐Hosieine A

Abstract

The first total synthesis of (-)-hosieine A was accomplished and features an unprecedented nitroso-ene cyclization to construct the 2-azabicyclo[3.2.1]octane ring system. Phosphine-enabled stereoselective bromohydrination provided interesting mechanistic insights into the anti-Markovnikov process. Also noteworthy is the retention of stereochemistry at C9 in the facile radical debromination initiated by Et3 B/air.

An Unexpected Transannular [4+2] Cycloaddition during the Total Synthesis of (+)‐Norcembrene 5

“…The Evans auxiliary for the stereoselective 1,4‐addition was attached by amidation of the lithiated oxazolidinone with the acid chloride formed in situ from 15 to furnish enone 13 in 81 % yield . Diastereoselective installation of the isopropenyl moiety was performed using freshly recrystallized CuBr⋅SMe 2 as the copper source . Under optimized conditions, compound 16 was obtained in quantitative yield as a single diastereomer.…”

“…[7] Diastereoselective installation of the isopropenyl moiety was performed using freshly recrystallized CuBr·SMe 2 as the copper source. [8] Under optimized conditions, compound 16 was obtained in quantitative yield as a single diastereomer. Subsequent reductive cleavage of the auxiliary directly afforded aldehyde 11 in 77 % yield.…”

Eine unerwartete transanulare [4+2]‐Cycloaddition während der Gesamtsynthese von (+)‐Norcembren 5

“…Dazu wurde das in situ gebildete Säurechlorid von 15 verwendet, und ergab 81 % des Enons 13 [7] Diastereoselektive Installation des Isopropenylrests wurde mittels frisch aufgereinigtem CuBr·SMe 2 als Kupferquelle durchgeführt. [8] Nach Optimierung der Bedingungen wurde 16 in quantitativen Ausbeuten als einziges Diastereomer erhalten. Darauf folgte die reduktive Abspaltung des Auxiliars zum Aldehyd 11 in 77 % Ausbeute.…”

Synthesis of Bridged Tetrahydrobenzo[b]azepines and Derivatives through an Aza‐Piancatelli Cyclization/Michael Addition Sequence

“…Biologicallyr elevant tetrahydrobenzo [b]azepinesand our strategy to prepare bridged tetrahydrobenzo [b]azepinesa nd related compounds. more,weconsidered that this protocol could be implemented to synthesize 2-azabicyclo[3.2.1]octanes,w hich are also challenging scaffolds in synthesis, [12] and bridged tetrahydrobenzo [b]oxepines,both motifs can be encountered in other natural products such as enokipodin A [13] and hosieine A. [14] In our preliminary investigations (Table 1), we explored the reactivity of 2-furylcarbinol 1a incorporating as ulfonamide group with 4-iodoaniline 2a using our standard catalytic system for the aza-Piancatelli cyclization (Ca(NTf 2 ) 2 (5 mol %) and nBu 4 NPF 6 (5 mol %)) in hexafluoroisopropanol (HFIP) [15] under air (Entry 1).…”