Highly Enantioselective Alk‐2‐enylation of Aldehydes through an Allyl‐Transfer Reaction

Abstract

Enantiomerenreine homoallylische Alkohole wie 1 (einfach aus einem (Alk‐2‐enyl)metallreagens mit (−)‐ oder (+)‐Menthon erhältlich) fungieren als Alk‐2‐enyldonoren für Aldehyde. Die Allylübertragung, die über einen sesselförmigen sechsgliedrigen Ring als Übergangszustand verläuft, liefert die α‐Addukte der homoallylischen Alkohole, 2, in guter Ausbeute mit >99 % ee. pTSA=p‐Toluolsulfonsäure.

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…In this context, the group of Nokami has described the preparation of linear (E)-homoallylic alcohols from chiral donors conveniently prepared from cheap and readily available (−)-or (+)-menthone. 127 The equatorial approach of allylic metal reagents (i.e., Grignard reagents) to the chiral menthone afforded the expected diastereomeric mixture of γ-adducts as major products in good overall yields. Importantly, when both crotyl adducts were separated and independently made to react with phenylpropanal, in the presence of p-toluenesulfonic acid monohydrate as catalyst, only the major isomer with the R configuration at the allylic position reacted.…”

Atom‐Economical Dimerization Strategy by the Rhodium‐Catalyzed Addition of Carboxylic Acids to Allenes: Protecting‐Group‐Free Synthesis of Clavosolide A and Late‐Stage Modification

“…Our synthesis proceeded from the menthone‐based Nokami crotyl‐transfer reagent22 6 a by treatment with the known homoallenyl aldehyde 7 23 (Scheme ), which could be readily prepared in multigram quantities in two steps 24. The resulting chiral homoallylic alcohol 5 was obtained in good yield (86 %) but with only 72 % ee .…”

“…[9a, 10b] At the same time,the interim structure 3 should bring av aluable allylester moiety into reach, which could then be further elaborated either by double crossmetathesis [18] with (Z)-butene and double stereoselective Simmons-Smith cyclopropanation [19] for the synthesis of the targeted natural product 1 or by other late-stage modifications with only little extra synthetic effort. [21] Our synthesis proceeded from the menthone-based Nokami crotyl-transfer reagent [22] 6a by treatment with the known homoallenyl aldehyde 7 [23] (Scheme 3), which could be readily prepared in multigram quantities in two steps. [20] In any case,this strategic approach to efficiently deliver symmetrical subunits of polyketide natural products is considered to be of more general interest, since it shows enormous potential for late-stage modification by diverted total synthesis,t hus enabling great possibilities for further biological screening.…”

The Stability of Organic Compounds

“…Tertiary homoallylic alcohols can formally undergo fragmentation into a ketone and an allyl anion [12,13]. If the homoallylic alcohol contains several bulky alkyl groups its ground state energy may be sufficiently high to enable C-C bond cleavage to occur under mild reaction conditions.…”