Stereo- and Regiochemical Divergence in the Substitution of a Lithiated Alk-1-en-3-yn-2-yl Carbamate: Synthesis of Highly Enantioenriched Vinylallenes

Stereo- and Regiochemical Divergence in the Substitution of a Lithiated Alk-1-en-3-yn-2-yl Carbamate: Synthesis of Highly Enantioenriched Vinylallenes or Alk-3-en-5-yn-1-ols

Link: http://www3.interscience.wiley.com/cgi-bin/abstract/114190082/ABSTRACT

From Prof. Dieter Hoppe's group at Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Münster, Germany

I think this is some interesting and intriguing chemistry presented in ACIEE EarlyView regarding the reactivity of organolithium in the presence of (-)-sparteine. It has been reported previously by the same research group that gamma-deprotonation of alkene carbamate of type 1, possessing negative-charge stabilizing group W (such as aryl, triorganosilyl, and 1-alkenyl groups), using n-BuLi in the presence of (-)-sparteine (2), a stereo-defined alkyllithium (3) could be generated which could add stereoselectively to electrophile to afford 4.

In the new development, when the W group was changed to an alkynyl group, the reactivity of the alkyllithium changed. That is when enyne 7 was deprotonated using n-BuLi/2 system, H(R) was selectively deprotonated and (S)-8 was produced.

When treated with acetone, (S)-8 added in an anti-SE' fashion to give allene (-)-(aR,E)-9a selectively (Method A). However, if (S)-8 was allowed to equilibrate over a longer period (15h), (R)-8 was produced and it added to acetone in the same anti-SE' fashion to give (+)-(aS,E)-9a instead (Method B). Method A was confirmed again with 4,4'-dibromobenzophenone to give (-)-(aR,E)-9b.

When (S)-8 was treated with ClTi(OiPr)3, lithium-titanium occurred that also inverted the C-metal center. The resulted organotitanium (S)-10 then added to acetone in the syn fashion at the allylic position to give homoallylic alcohol (S,Z)-11a (Method C). The TS for this addition was proposed to be 6-membered chairlike Zimmerman-Traxler transition state. As (R)-8, lithium-titanium exchange led to (R)-10, which afforded (R,Z)-11a upon addition to acetone (Method D).

Finally, two other experiments were performed to confirm the mechanisms of both organolithium and organotitanium. In the first experiment, (R)-8 was trapped with Ph3SnCl to give allene 9c, structure of which was confirmed by x-ray. Because previous study of stannylation of propargyllithium/2 system showed the mechanism to be anti-SE', thus this result showed that the configuration of 8 was R.

The kinetic organolithium (S)-8 was transmetalated with titanium to form (S)-10 which reacted with chiral aldehyde 12 to give 11b, the structure of which was confirmed by x-ray. Because it is known that chiral alpha-(carbamoyloxy)allyltitanium compounds react with chiral aldehydes with strict chirality transfer from the Zimmerman–Traxler transition state. Therefore, configuration shown in 11 must be generated from (S)-10, which in turn was obtained by inversion of configuration of (S)-8.

Reaction of 8 with other electrophiles were also reported as summarized in the table below.

Conclusion for the current system:

1) Organolithium ---> anti-SE' addition to give allenyl alcohols
2) Lithium-titanium exchange ---> inversion of configuration
3) Organotitanium ---> syn addition via Zimmerman-Traxler transition state to give homoallylic alcohol
4) Organolithium was generated stereoselectively with n-BuLi/(-)-sparteine system. This kinetic organolithium can epimerize to give the opposite configuration upon prolonged reaction time.